Patent Application
20240138975
The present disclosure concerns aspects of medical implant devices incorporating materials inclusive of a plurality of fibers that comprise an electrospun silk. The present disclosure also concerns aspects of methods of forming such medical implant devices.
The heart can suffer from various valvular diseases or malformations that result in significant malfunctioning of the heart and ultimately require replacement of the native heart valve with an artificial valve. Human heart valves, which include the aortic, pulmonary, mitral, and tricuspid valves, function essentially as one-way valves operating in synchronization with the pumping heart. The valves allow blood to flow downstream but block blood from flowing upstream. Diseased heart valves exhibit impairments such as narrowing the valve or regurgitation, which inhibits the valves' ability to control blood flow. Such impairments reduce the heart's blood-pumping efficiency and can be a debilitating and life-threatening condition. For example, valve insufficiency can lead to conditions such as heart hypertrophy and dilation of the ventricle. Thus, extensive efforts have been made to develop methods and apparatuses to repair or replace impaired heart valves.
Prostheses exist to correct problems associated with impaired heart valves. For example, mechanical and tissue-based heart valve prostheses can be used to replace impaired native heart valves. More recently, substantial effort has been dedicated to developing replacement heart valves, particularly tissue-based replacement heart valves that can be delivered with less trauma to the patient than through open-heart surgery. Replacement valves are being designed to be delivered through minimally invasive procedures and even percutaneous procedures. Such replacement valves often include a tissue-based valve body connected to an expandable frame that is then delivered to the native valve's annulus.
These replacement valves are often intended to at least partially block blood flow. However, a problem occurs when blood flows around the valve on the outside of the prosthesis. For example, in the context of replacement heart valves, paravalvular leakage has proven particularly challenging. An additional challenge relates to the ability of such prostheses to be secured relative to intra-luminal tissue, e.g., tissue within any body lumen or cavity, in an atraumatic manner. Further challenges arise when trying to controllably deliver and secure such prostheses in a location such as at a native mitral valve. These replacement valves are often intended to at least partially block blood flow.
Because of the drawbacks associated with conventional open-heart surgery, percutaneous and minimally-invasive surgical approaches are garnering intense attention. In one technique, a prosthetic valve is configured to be implanted in a much less invasive procedure by way of catheterization. For instance, U.S. Pat. Nos. 5,411,522 and 6,730,118, which are incorporated herein by reference, describe collapsible transcatheter heart valves that can be percutaneously introduced in a compressed state on a catheter and expanded in the desired position by balloon inflation or by utilization of a self-expanding frame or stent. In yet another example, U.S. U.S. Publication Nos. 2014/0277390, 2014/0277422, 2014/0277427, and 2015/0328000, and 2019/0328515, which are incorporated herein by reference in their entirety, describe heart valve prostheses for replacing a native mitral valve, including a self-expanding frame with a plurality of anchoring members that are designed be deployed within a body cavity and prevent axial flow of fluid around an exterior of the prosthesis.
However, the manufacturing of such implantable devices can be cumbersome and expansive and often limiting. For example, the textile used as a part of the paravalvular leakage sealing material is often formed from woven or knitted fabric comprising medical-grade polyester (PET) filaments. The process requiring to produce such a fabric is time-consuming, and the resulting product has multiple limitations. For example, the PET filaments used for such construction are limited to larger diameter filaments. Currently, the minimum applicable diameter of PET filament is about 10 microns that can affect other properties of the formed textile, such as a textile surface area, smoothness of the surface, tensile properties of the fabric, and the like. In addition, the PET-based fabrics are not biodegradable and/or bioresorbable that further limits the use of such fabrics.
Also, the manufacturing of other parts of the valve has additional challenges and limitations. For example, valve leaflets are often formed from the material that is obtained from a living tissue that makes such production more complicated and also expansive.
Thus, there is still a need for implantable devices that comprise materials having the desired mechanical and chemical properties that are easy to manufacture. These needs and others are at least partially satisfied by the present disclosure.
Some of the aspects of the present disclosure relate to implantable prosthetic valves. Some aspects relate to an implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; a leaflet structure positioned within the frame; an inner skirt positioned along the inner surface of the frame; at least one outer skirt positioned around the outer surface of the frame; wherein at least a portion of one of the leaflet structure, the inner skirt, or the at least one outer skirt comprises a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; and wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration.
In yet other aspects, disclosed is the implantable prosthetic valve, wherein at least a portion of the inner skirt comprises the material comprising the plurality of fibers comprising the electrospun silk, and wherein the material present in the at least a portion of the inner skirt is a first material. In one aspect, disclosed is the implantable prosthetic valve of the preceding aspects, wherein at least a portion of the outer skirt comprises the material comprising the plurality of fibers comprising the electrospun silk, and wherein the material present in the at least a portion of the outer skirt is a second material. In yet another aspect, disclosed is the implantable prosthetic valve of the preceding aspects, wherein at least a portion of the leaflet structure comprises the material comprising the plurality of fibers comprising the electrospun silk, and wherein the material present in the at least a portion of the leaflet structure is a third material. Also disclosed herein are aspects wherein the first, second, and third materials are the same or different.
Still disclosed herein are the aspects where each fiber of the plurality of fibers has a first extending direction and a plurality of undulations. In some aspects, the first extending direction can comprise a circumferential direction, a radial direction, or a combination thereof. In still further aspects, the described plurality of undulations can be present in the collapsed configuration. In still further aspects, the plurality of undulations can be configured to straighten when the implantable prosthetic valve is in the expanded configuration.
In one aspect, disclosed is the implantable prosthetic valve where the valve further comprises an adhesive material disposed between at least a portion of the annular frame and at least a portion of the outer skirt and/or between at least a portion of the annular frame and at least a portion of the inner skirt. While in other aspects, disclosed is the implantable prosthetic valve where at least a portion of the inner skirt is attached to the annular frame by direct electrospinning of the plurality of fibers on at least a portion of the inner surface of the annular frame. Still in further aspects, disclosed is the implantable prosthetic valve where at least a portion of the outer skirt is attached to at least a portion of the annular frame by direct electrospinning of the plurality of fibers on at least a portion of the outer surface of the annular frame.
Still, further, the implantable prosthetic valves of any one of the preceding aspects where at least a portion of the plurality of fibers have a random orientation are also disclosed. While in other aspects, at least a portion of the plurality of fibers can have a predetermined aligned orientation.
In some exemplary aspects, the plurality of fibers can further comprise other than silk materials. In some exemplary aspects, the plurality of fibers can further comprise a resorbable material, a non-resorbable material, or any combination thereof. For example, in some aspects, the plurality of fibers can further comprise thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyurethane (PU); implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
Still further disclosed is an aspect where at least a portion of the plurality of fibers comprises a bicomponent fiber. It is understood that in such exemplary aspects, the bicomponent fiber can comprise a side-by-side configuration, a sheath-core configuration, an islands-in-the-sea configuration, a tri-lobal, a segmented pie configuration, or any combination thereof. While in some exemplary and unlimiting aspects, the bicomponent fiber can comprise the sheath-core configuration.
In some aspects, a sheath and/or a core of the bicomponent fiber comprises a resorbable material, non-resorbable material, or any combination thereof. In certain aspects, a sheath of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof. While is still further exemplary aspects, a sheath of the bicomponent fiber can comprise silk, while a core of the bicomponent fiber can comprise one or more of thermoplastic polyurethane (TPU), polyurethane (PU) implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
Also disclosed herein are aspects where the plurality of fibers can have an average diameter from about 3 nm to about 15,000 nm. While in other aspects, at least a portion of the first material, and/or the second material, and/or third material can exhibit porosity. In such exemplary and unlimiting aspects, the at least a portion of the first material, and/or the second material, and/or third material can have an average pore size from about 100 nm to about 100 μm. In still further aspects, wherein the first material and/or the second material, and/or third material can comprise a plurality of layers, wherein each of the plurality of layers comprises electrospun silk, and wherein each of the plurality of layers is disposed on each other. In such exemplary aspects, at least a first portion of the plurality of layers has a surface area that is substantially smaller than a surface area of a second portion of the plurality of layers surface area.
In still further aspects, the first material and/or the second material, and/or third material used in any of the disclosed above implantable prosthetic devices can exhibit a tensile strength from greater than 0 MPa to about 20 MPa. While in other aspects, the first material and/or the second material, and/or third material can exhibit an elongation at break from greater than 0% to about 600%. In yet still further aspects, the first material and/or the second material, and/or third material can exhibit a water contact angle from about 0° to about 180°.
Also disclosed are the aspects where at least a portion of the annular frame is surface modified. In certain and unlimiting aspects, at least a portion of the annular frame is plasma treated. While in other aspects, at least a portion of the inner skirt can be surface modified. In such exemplary aspects, at least a portion of the inner skirt comprising the first material is plasma treated. While in still further aspects, at least a portion of the outer skirt can be surface modified. In such exemplary aspects, at least a portion of the outer skirt comprising the second material can be plasma treated. Still further, in some aspects, also at least a portion of the leaflet system can be surface modified. In such exemplary aspects, wherein at least a portion of the leaflet structure comprising the third material is plasma treated.
Further disclosed herein is an aspect where the first material and/or the second material, and/or third material is at least partially biodegradable. While in other aspects, the first material and/or the second material, and/or third material is at least partially bioresorbable. In still further aspects, the first material and/or the second material, and/or third material can be both at least partially biodegradable and at least partially bioresorbable. In yet further aspects, the first material and/or the second material, and/or third material as described in any preceding aspects, can be at least partially degradable. In still further aspects, the first material and/or the second material, and/or third material as described in any preceding aspects, can be a scaffold material.
In still further aspects, the disclosed herein implanted valves can have at least a portion of the inner skirt further comprising a first perforated material having a first surface facing the annular frame and an opposite second surface and wherein the first material can comprise the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the first perforated material.
In yet other aspects, at least a portion of the outer skirt can further comprise a second perforated material having a first surface facing the annular frame and an opposite second surface and wherein the second material comprises the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the second perforated material.
Also disclosed are aspects, where at least a portion of the leaflet structure comprises a third perforated material having a first surface facing the annular frame and an opposite second surface and wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the third perforated material.
In addition or in the alternative, also disclosed are aspects where at least a portion of the leaflet structure comprises a third perforated material having a first surface facing the annular frame and an opposite second surface and wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the third perforated material.
Still further, in some aspects, the first perforated material, the second perforated material and/or the third perforated material can be the same or different.
Also disclosed are aspects where at least a portion of the first surface of the first material comprises a first auxiliary layer. While in the alternative or additional aspects, at least a portion of the second surface of the first material comprises a first auxiliary layer.
In some aspects disclosed is the implantable prosthetic valve where the first auxiliary layer present on the second surface of the first material is the same or different as the first auxiliary layer present on the first surface of the first material.
Yet in other aspects, wherein at least a portion of the first surface of the second material comprises a second auxiliary layer.
Still further disclosed are aspects where at least a portion of the second surface of the second material comprises a second auxiliary layer.
Also disclosed are aspects where the second auxiliary layer present on the second surface of the second material is the same or different as the second auxiliary layer present on the first surface of the second material.
Still further disclosed are aspects where at least a portion of the first surface of the third material comprises a third auxiliary layer. While in other aspects, at least a portion of the second surface of the third material comprises a third auxiliary layer.
In still further aspects, the third auxiliary layer present on the second surface of the third material is the same or different as the third auxiliary layer present on the first surface of the third material.
While in still further aspects, each of the first, second or third auxiliary layers can be the same or different.
In some aspects, the first, second, and/or third perforated material can comprise a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers that are resorbable, non-resorbable or a combination thereof. In some exemplary and unlimiting aspects, the first, second, and/or third perforated material can comprise a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers selected from polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA) or a combination thereof, or natural/regenerated fibers selected from cotton, silk, linen, cellulose acetate, collagen, or a combination thereof.
In yet other aspects, the first, second, and/or third auxiliary layer configured to impart to at least a portion of the first, second, and/or third material hydrophobic or hydrophilic properties, elastomeric properties, mechanical resilience, adhesive properties, tissue-in-growth inhibition, or any combination thereof.
In still further aspects, the first, second, and/or third auxiliary layer comprises one or more of resorbable, non-resorbable, or a combination thereof materials. In addition or in the alternative also disclosed are aspects where the first, second, and/or third auxiliary layer comprises one or more thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, or polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA).
In some further aspects, at least a portion of the inner skirt further comprises at least two layers of the first perforated material, wherein the first material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the first perforated material, and wherein at the two layers of the first perforated material are at least partially coupled to each other.
While in other aspects, at least a portion of the outer skirt can further comprise at least two layers of the second perforated material, wherein the second material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the second perforated material and wherein at the two layers of the second perforated material are at least partially coupled to each other.
Also disclosed are aspects where at least a portion of the leaflet structure further comprises at least two layers of the third perforated material, wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the third perforated material, and wherein at the two layers of the third perforated material are at least partially coupled to each other.
In still further aspects, wherein at least a portion of the second surface of the first material is disposed on the first surface of the first perforated material. While in other aspects, at least a portion of the first surface of the first material is disposed on the second surface of the first perforated material. In yet still further aspects, at least a portion of the second surface of the second material is disposed on the first surface of the second perforated material.
Still, in further exemplary and unlimiting aspects, at least a portion of the first surface of the second material is disposed on the second surface of the second perforated material. Yet, in other aspects, at least a portion of the second surface of the third material is disposed on the first surface of the third perforated material.
In some aspects, at least a portion of the first surface of the third material is disposed on the second surface of the third perforated material.
While in other aspects, wherein at least a portion of the first auxiliary layer and the first perforated material is coupled to each other.
Still further disclosed are aspects where at least a portion of the second auxiliary layer and the second perforated material are coupled to each other. While in other aspects, at least a portion of the third auxiliary layer and the third perforated material are coupled to each other.
Also disclosed herein, in some aspects, is an article comprising a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk, wherein the article has a collapsed configuration and an expanded configuration, and wherein the article is a part of an implantable device. In such exemplary aspects, the article is a paravalvular leak sealing article. In still further aspects, the paravalvular leak sealing article can comprise an inner skirt comprising a first material comprising a plurality of fibers comprising an electrospun silk and where the inner skirt is configured to be positioned on at least a portion of an inner surface of an annular frame of the implantable prosthetic device, wherein the first material has a first surface facing the annular frame and an opposite second surface. While in still further aspects, the paravalvular leak sealing article can comprise an outer skirt comprising a second material comprising a plurality of fibers comprising an electrospun silk and where the outer skirt is configured to be positioned on at least a portion of an outer surface of an annular frame of the implantable prosthetic device, wherein the second material has a first surface facing the annular frame and an opposite second surface.
Still further also disclosed herein are aspects where the article can comprise a leaflet structure comprising a third material comprising a plurality of fibers comprising an electrospun silk and where the leaflet structure, is configured to be positioned within at least a portion of an annular frame of the implantable prosthetic device, wherein the third material has a first surface facing the annular frame and an opposite second surface. It is understood that in the aspects disclosed herein, the disclosed material comprises the first material, or the second material, or the third material, or a combination thereof. In yet further aspects, the disclosed herein the first, the second, and the third materials can be the same or different.
In still further aspects, each fiber of the plurality of fibers has a first extending direction and a plurality of undulations. Further, in such exemplary aspects, the first extending direction can comprise a circumferential direction, a radial direction, or a combination thereof. Still, further, the plurality of undulations, as described in any preceding aspect, are present in the collapsed configuration. It is further understood that in such aspects, the plurality of undulations are configured to straighten when the article is in the expanded configuration.
In certain aspects, at least a portion of the inner skirt is attached to at least a portion of the annular frame by direct electrospinning of the plurality of fibers. While in other exemplary aspects, at least a portion of the outer skirt is attached to at least a portion of the annular frame by direct electrospinning of the plurality of fibers.
Also disclosed are articles where wherein the plurality of fibers further comprise a resorbable material, a non-resorbable material, or a combination thereof. In some aspects, at least a portion of the plurality of fibers has a random orientation. While in other aspects, at least a portion of the plurality of fibers has a predetermined aligned orientation. In such aspects, the articles disclosed in any of the preceding aspects can also comprise a plurality of fibers, where the plurality of fibers further comprises thermoplastic polyurethane (TPU), polyurethane (PU) implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
In still further exemplary aspects, at least a portion of the plurality of fibers can comprise a bicomponent fiber. It is understood that the bicomponent fiber can comprise any known configuration. In some exemplary and unlimiting aspects, the bicomponent fiber can comprise a side-by-side configuration, a sheath-core configuration, a tri-lobal, an islands-in-the-sea configuration, a segmented pie configuration, or any combination thereof. While in one aspect, the bicomponent fiber comprises the sheath-core configuration.
In certain aspects, a sheath and/or core of the bicomponent fiber comprises a resorbable material, a non-resorbable material, or a combination thereof. In yet other aspects, a sheath of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
While is still further exemplary aspects, a sheath of the bicomponent fiber can comprise silk, while a core of the bicomponent fiber can comprise one or more of thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
In still further aspects, the article, as described in any preceding aspects, can comprise a plurality of fibers, wherein the plurality of fibers have an average diameter from about 3 nm to about 15,000 nm. While in other exemplary aspects, at least a portion of the first material and/or the second material and/or the third material can exhibit porosity. While in still further exemplary aspects, the at least a portion of the first material and/or the second material and/or the third material can have an average pore size from about 100 nm to about 100 μm.
Also disclosed herein are aspects of the article, where at least a portion of the first material and/or the second material and/or the third material comprise a plurality of layers, wherein each of the plurality of layers comprises electrospun silk, and wherein each of the plurality of layers is disposed on each other. In such exemplary aspects, at least a first portion of the plurality of layers has a surface area that is substantially smaller than a surface area of a second portion of the plurality of layers surface area.
Still further disclosed herein are aspects of the article, where at least a portion of the first material and/or the second material and/or the third material can exhibit tensile strength from greater than 0 MPa to about 20 MPa. While further disclosed herein are aspects of the article, where at least a portion of the first material and/or the second material and/or the third material can exhibit elongation at break from greater than 0% to about 600%. In still further aspects, at least a portion of the first material and/or the second material and/or the third material can exhibit a water contact angle from about 0° to about 180°. It is understood that also disclosed herein are aspects of the article, where at least a portion of the first material and/or the second material and/or the third material can exhibit the disclosed above tensile strength, elongation, and/or a water contact angle.
In still further aspects, disclosed herein are the articles as described in any one of preceding aspects, where at least a portion of the first material, and/or the second material, and/or the third material is surface modified by any known in the art methods. In some exemplary aspects, at least a portion of the first material comprising the plurality of fibers is plasma treated. While in other exemplary aspects, at least a portion of the second material is plasma treated. While in still further exemplary aspects, at least a portion of the third material is plasma treated.
In certain aspects, at least a portion of the first material and/or the second material and/or the third material can be at least partially biodegradable. While in other aspects, at least a portion of the first material and/or the second material and/or the third material can be at least partially bioresorbable. While in still further aspects, at least a portion of the first material and/or the second material and/or the third material can be at least partially degradable. It is understood, however, that also disclosed herein are the aspects where at least a portion of the first material and/or the second material and/or the third material is at least partially biodegradable and/or at least partially bioresorbable and/or at least partially degradable. In yet further aspects, at least a portion of the first material and/or the second material and/or the third material as described in any preceding aspects can be also be configured to be a scaffold material.
Also disclosed herein articles, where at least a portion of the inner skirt further comprises a first perforated material having a first surface facing the annular frame and an opposite second surface and wherein the first material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the first perforated material.
In still further aspects, disclosed are articles where at least a portion of the outer skirt further comprises a second perforated material having a first surface facing the annular frame and an opposite second surface and wherein the second material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the second perforated material.
Also disclosed are articles, where at least a portion of the leaflet structure comprises a third perforated material having a first surface facing the annular frame and an opposite second surface and wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the third perforated material.
In some additional or alternative aspects, the first perforated material, the second perforated material and/or the third perforated material can be the same or different.
While yet in other aspects, disclosed are articles where at least a portion of the first surface of the first material comprises a first auxiliary layer. While in still other aspects, at least a portion of the second surface of the first material comprises a first auxiliary layer. Also disclosed are articles where the first auxiliary layer present on the second surface of the first material is the same or different as the first auxiliary layer present on the first surface of the first material.
In addition or in the alternatives disclosed are articles where at least a portion of the first surface of the second material comprises a second auxiliary layer. In some exemplary aspects, at least a portion of the second surface of the second material comprises a second auxiliary layer. In still further aspects, the second auxiliary layer present on the second surface of the second material is the same or different as the second auxiliary layer present on the first surface of the second material.
In addition or in the alternatives disclosed are articles where at least a portion of the first surface of the third material comprises a third auxiliary layer. In some exemplary aspects, at least a portion of the second surface of the third material comprises a third auxiliary layer. In still further aspects, the third auxiliary layer present on the second surface of the third material is the same or different as the third auxiliary layer present on the first surface of the third material.
Still, further, each of the first, second or third auxiliary layers can be the same or different
Also disclosed herein are articles where the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises a resorbable material, a non-resorbable material, or a combination thereof. In yet other aspects, the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers selected from polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyamide, polyethylene terephthalate (PET, polyethersulfone, poly-lactic-co-glycolic acid (PLGA) or a combination thereof or natural/regenerated fibers selected from cotton, silk, linen, cellulose acetate, collagen, or a combination thereof.
In addition or in the alternative, disclosed are articles where the first, second, and/or third auxiliary layer configured to impart to at least a portion of the first, second, and/or third material hydrophobic or hydrophilic properties, elastomeric properties, mechanical resilience, adhesive properties, tissue-in-growth inhibition, or any combination thereof.
In yet further aspects, disclosed are articles where the first, second, and/or third auxiliary layer comprises one or more of a resorbable material, a non-resorbable material, or a combination thereof. Yet in other aspects, the first, second, and/or third auxiliary layer comprises one or more thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, or polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), polyamide, polyethylene, terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA).
Also disclosed are articles where at least a portion of the inner skirt further comprises at least two layers of the first perforated material, wherein the first material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the first perforated material, and wherein at the two layers of the first perforated material are at least partially coupled to each other.
In some aspects, disclosed are articles where at least a portion of the outer skirt further comprises at least two layers of the second perforated material, wherein the second material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the second perforated material and wherein at the two layers of the second perforated material are at least partially coupled to each other.
While in other aspects, disclosed are articles where at least a portion of the leaflet structure further comprises at least two layers of the third perforated material, wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the third perforated material; and wherein at the two layers of the third perforated material are at least partially coupled to each other.
In some exemplary and unlimiting aspects disclosed are articles where at least a portion of the second surface of the first material is disposed on the first surface of the first perforated material. Yet, in other aspects, at least a portion of the first surface of the first material is disposed on the second surface of the first perforated material.
In still further aspects, at least a portion of the second surface of the second material is disposed on the first surface of the second perforated material. While in other aspects, at least a portion of the first surface of the second material is disposed on the second surface of the second perforated material. While in still further aspects, at least a portion of the second surface of the third material is disposed on the first surface of the third perforated material.
Also disclosed are aspects directed to the articles having at least a portion of the first surface of the third material be disposed on the second surface of the third perforated material.
In some aspects, at least a portion of the first auxiliary layer and the first perforated material are coupled to each other. While in other aspects, at least a portion of the second auxiliary layer and the second perforated material are coupled to each other. While in still further aspects, at least a portion of the third auxiliary layer and the third perforated material is coupled to each other.
Also disclosed herein are methods of forming an implantable prosthetic valve. In such aspects, the methods comprise: a) providing an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; b) forming an inner skirt comprising a first material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; c) forming an outer skirt comprising a second material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; d) attaching the inner skirt to at least a portion of the inner surface of the annular frame and attaching the outer skirt to at least a portion of the outer surface of the annular frame, wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration.
In some aspects, the step of forming the inner skirt and the step of attaching the inner skirt can occur simultaneously. Yet, in other aspects, the step of forming the inner skirt can occur prior to the step of attaching.
In addition or in the alternative disclosed are methods where the step of forming the outer skirt and the step of attaching the outer skirt occurs simultaneously. While in other aspects, the step of forming the outer skirt can occur prior to the step of attaching.
In some methods, the step of attaching the inner skirt occurs before or after the step of attaching the outer skirt.
In addition or in the alternative, the methods disclosed herein further comprise positioning a leaflet structure comprising a third material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises an electrospun silk within at least a portion of the annular frame.
In some aspects, the step of positioning the leaflet structure can occur before or after the step of forming the inner skirt and/or outer skirt.
Also disclosed are the methods where the first material, the second, and the third material are the same or different.
In addition or in the alternative disclosed are methods where the step of simultaneously forming and attaching the inner skirt to the at least a portion of the inner surface of the annular frame comprises forming the first material by directly electrospinning at least a portion of the plurality of fibers through at least one spinneret from a first solution comprising a first predetermined concentration of a silk fibroin at a predetermined extrusion rate at the at least a portion of the inner surface of the annular frame.
In further aspects disclosed are the methods where the step of forming the first material comprises electrospinning at least a portion of the plurality of fibers through at least one spinneret from a first solution comprising a first predetermined concentration of a silk fibroin at a predetermined extrusion rate on a first predetermined mandrel.
Also disclosed are methods where the step of attaching comprises i) shaping the first material to a predetermined dimension and ii) attaching the first material to the at least a portion of the inner surface of the annular frame.
In addition or in the alternative disclosed are methods where the step of simultaneously forming and attaching the outer skirt to the at least a portion of the outer surface of the annular frame comprises forming the second material by directly electrospinning at least a portion of the plurality of fibers through at least one spinneret from a second solution comprising a second predetermined concentration of a silk fibroin at a predetermined extrusion rate the at least a portion of the outer surface of the annular frame.
Yet, in other aspects, the step of forming the second material comprises electrospinning at least a portion of the plurality of fibers through at least one spinneret from a second solution comprising a second predetermined concentration of a silk fibroin at a predetermined extrusion rate on a second predetermined mandrel.
In addition or in the alternative disclosed are methods where the step of attaching comprises i) shaping the second material to a predetermined dimension and ii) attaching the second material to the at least a portion of the outer surface of the annular frame.
In still further methods, the third material can be formed by the electrospinning of the plurality of fibers on a third predetermined mandrel from a third solution comprising a third predetermined concentration of a silk fibroin at a predetermined extrusion rate. In some methods, the third material can be laser cut to form the leaflet structure
In some exemplary and unlimiting methods, prior to forming the inner skirt and/or the outer skirt, at least a portion of the annular frame is plasma treated. While in other methods, prior to the step attaching the inner skirt and/or the outer skirt to the at least a portion of the inner surface and/the outer surface of the annular frame, respectively, an adhesive material is applied to the at least a portion of the inner surface and/or the outer surface of the annular frame.
In some aspects in addition or in the alternative to any one of the preceding aspects, during the electrospinning of the at least a portion of the plurality of fibers to form the first material, the at least a portion of the inner surface of the annular frame can be positioned at a first predetermined distance from the at least one extrusion spinneret. Yet in other aspects, during the electrospinning of the at least a portion of the plurality of fibers to form the second material, the at least a portion of the outer surface of the annular frame can be positioned at a second predetermined distance from the at least one extrusion spinneret.
In some exemplary aspects, the at least one extrusion spinneret is positioned outside of the annular frame.
While in other aspects, the at least one extrusion spinneret is positioned within at least a portion of an inner space of the annular frame, wherein the inner space is defined by a circumference of the inner surface of the annular frame. In such exemplary and unlimiting aspects, the methods can further comprise at least one additional extrusion spinneret that is positioned outside of the annular frame.
In such exemplary methods, the electrospinning can occur simultaneously from the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and from the at least one additional spinneret that is positioned outside of the annular frame. While in other methods, the electrospinning can occur first from the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and then from the at least one additional spinneret that is positioned outside of the annular frame.
In yet other methods, the electrospinning can occur first from the at least one additional spinneret that is positioned outside of the annular frame and then from the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame. In still further aspects, the electrospinning is performed by cycling.
In some aspects, the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and the at least one additional spinneret positioned outside of the annular frame has an extrusion rate that is the same or different. While in other aspects, each of the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular space and the at least one additional spinneret positioned outside are configured to electrospun a plurality of fibers from a solution having the same or different concentration of a silk fibroin.
Also disclosed are the methods where the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame at a third distance from the annular frame and is configured to be moved within the inner space of the annular frame. In still further aspects, the third predetermined distance from the annular frame is adjustable.
In some aspects, the at least one additional spinneret positioned outside of the annular frame is positioned at a fourth predetermined distance from the annular frame. In yet further aspects, the fourth predetermined distance from the annular frame is adjustable. In still further aspects, the first, second, third and/or fourth predetermined distances are the same or different.
In some aspects, disclosed are methods where the plurality of fibers formed by the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and the at least one additional spinneret positioned outside of the annular frame are consolidated.
In some additional and unlimiting aspects, during the electrospinning of the at least a portion of the plurality of fibers to form the third material, the at least a portion of the third predetermined mandrel can be positioned at a third predetermined distance from the at least one extrusion spinneret.
Also disclosed are methods, where during the electrospinning of the at least a portion of the plurality of fibers to form the first material and/or the second material and/or the third material, the at least a portion of the inner surface of the annular frame and/or the at least a portion of the outer surface of the annular frame and/or the at least a portion of the first, second and/or third predetermined mandrels are positioned at a distance from the at least one extrusion spinneret such that the distance is varied during the electrospinning to form one or more plurality of layers within at least a portion of the first material and/or the second material and/or the third material.
In some methods, at least a portion of the annular frame is positioned on a rotational drum configured to rotate at a predetermined speed. While in other methods, the first, second, and/or third predetermined mandrels are configurated to be rotational or stationary.
Also disclosed are methods where a first predetermined voltage is applied between the rotational drum and the at least one spinneret. Yet, in other aspects, a second predetermined voltage is applied between the first, second and/or third predetermined mandrels and the at least one spinneret.
In some methods, the at least one spinneret comprises a needle.
Yet, in other methods, the at least one spinneret is a part of an assembly comprising a plurality of spinnerets. In such exemplary and unlimiting methods, the assembly can comprise a plurality of needle-less spinnerets.
Also disclosed are methods where the plurality of fibers present in the first material and/or the second material and/or the third material comprise a first extending direction and a plurality of undulations. In such exemplary methods, the first extending direction can comprise a circumferential direction, a radial direction, or a combination thereof. In still further aspects, the plurality of undulations are present in the collapsed configuration of the implantable prosthetic valve. While in other aspects, the plurality of undulations are configured to straighten when the implantable prosthetic valve is in the expanded configuration.
In some methods, at least a portion of the plurality of fibers present in the first material and/or the second material and/or the third material has a random orientation. While in other methods, at least a portion of the plurality of fibers present in the first material and/or the second material and/or the third material has a predetermined aligned orientation.
In addition or in the alternative disclosed are methods, where the plurality of fibers present in the first material and/or the second material and/or the third material further comprise a resorbable material, a non-resorbable material, or a combination thereof. In yet other methods, the plurality of fibers present in the first material and/or the second material and/or the third material further comprise thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
In some methods, wherein the plurality of fibers are disposed by electrospinning through the at least one spinneret from the first solution and/or the second solution and/or the third solution further comprising a predetermined concentration of a resorbable material, a non-resorbable material, or a combination thereof. In such exemplary and unlimiting aspects, the plurality of fibers are disposed by electrospinning through the at least one spinneret from the first solution and/or the second solution and/or the third solution, further comprising a predetermined concentration of the thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof at a predetermined extrusion rate.
While in other methods, at least a portion of the plurality of fibers present in the first material and/or the second material, and/or the third material comprises a bicomponent fiber. In such exemplary and unlimiting methods, the bicomponent fiber comprises a side-by-side configuration, a sheath-core configuration, a tri-lobal, an islands-in-the-sea configuration, a segmented pie configuration, or any combination thereof.
In some aspects, the bicomponent fiber can comprise the sheath-core configuration. For example, disclosed are methods where wherein a sheath and a core of the bicomponent fiber comprises a resorbable material, a non-resorbable material, or a combination thereof. Yet in other methods, a sheath of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
While also disclosed are methods where a sheath of the bicomponent fiber comprises silk and wherein a core of the bicomponent fiber comprises one or more of thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
In some aspects, the bicomponent fibers are disposed by electrospinning through at least two concentric spinnerets, wherein an outer spinneret is configured to extrude a sheath fiber from a fourth solution comprising a fourth predetermined concentration of silk fibroin, and wherein an inner spinneret is configured to extrude a core fiber from a fifth solution comprising a predetermined concentration of a resorbable material, a non-resorbable material, or a combination thereof. In such exemplary and unlimiting aspects, the bicomponent fibers can be disposed by electrospinning through at least two concentric spinnerets, wherein an outer spinneret is configured to extrude a sheath fiber from a fourth solution comprising a fourth predetermined concentration of silk fibroin, and wherein an inner spinneret is configured to extrude a core fiber from a fifth solution comprising a predetermined concentration of thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof at a predetermined extrusion rate.
Also disclosed are methods where the plurality of fibers present in the first material and/or the second material and/or the third material have an average diameter from about 3 nm to about 15,000 nm.
In some methods, at least a portion of the first material and/or the second material and/or the third material exhibit porosity. In such exemplary methods, the at least a portion of the first material and/or the second material, and/or third material have an average pore size from about 100 nm to about 100 μm.
In addition or in the alternative, disclosed are methods where the first material and/or the second material, and/or third material comprise a plurality of layers, wherein each of the plurality of layers comprises electrospun silk, and wherein each of the plurality of layers is disposed on each other.
In some aspects disclosed are methods where the at least a first portion of the plurality of layers has a surface area that is substantially smaller than a surface area of a second portion of the plurality of layers surface area.
Yet in other aspects disclosed are methods, where the first material and/or the second material and/or the third material exhibit tensile strength from greater than 0 MPa to about 20 MPa. In still further aspects, the first material and/or the second material and/or the third material can exhibit elongation at break from greater than 0% to about 600%. While still in further aspects, the first material and/or the second material and/or the third material exhibit a water contact angle from about 0° to about 180°.
In some aspects, at least a portion of the first material and/or the second material and/or the third material is biodegradable. Yet, in other aspects, at least a portion of the first material and/or the second material and/or the third material is bioresorbable. Still, in other aspects, at least a portion of the first material and/or the second material and/or the third material is degradable. While still in further aspects, at least a portion of the first material and/or the second material and/or the third material is configured to be a scaffold material.
In some additional or alternative aspects, at least a portion of the plurality of fibers at present in the first material and/or the second material and/or the third material is plasma treated after electrospinning.
Also disclosed are aspects where at least a portion of the formed first material is disposed on a first perforated material having a first surface and an opposite second surface, prior to the step of attaching, and wherein the first material is disposed on the first surface and/or the second surface of the first perforated material.
In some methods disclosed herein, the step of attaching comprises coupling the first surface of the first perforated material to at least a portion of the annular frame.
While in other methods, at least a portion of the formed second material is disposed on a second perforated material having a first surface and an opposite second surface, prior to the step of attaching, and wherein the second material is disposed on the first surface and/or the second surface of the second perforated material. In such exemplary and unlimiting methods, the step of attaching comprises coupling the first surface of the second perforated material to at least a portion of the annular frame.
Also disclosed are the methods where at least a portion of the leaflet structure is disposed on a third perforated material having a first surface and an opposite second surface and wherein the third material is disposed on the first surface and/or the second surface of the third perforated material. It is understood that in such exemplary and unlimiting aspects, the first perforated material, the second perforated material and/or the third perforated material are the same or different.
Also disclosed are methods comprising disposing a first auxiliary layer at at least a portion of the first surface of the first material. For example, in some methods, a first auxiliary is disposed at at least a portion of the second surface of the first material. Yet, in other methods, the first auxiliary layer present on the second surface of the first material is the same or different as the first auxiliary layer present on the first surface of the first material.
In addition or in the alternative disclosed are methods comprising a second auxiliary layer at at least a portion of the first surface of the second material. In some aspects, the methods disclosed herein comprise disposing a second auxiliary layer at at least a portion of the second surface of the second material. In some exemplary and unlimiting methods, the second auxiliary layer present on the second surface of the second material is the same or different as the second auxiliary layer present on the first surface of the second material.
Also disclosed are methods comprising disposing a third auxiliary layer at at least a portion of the first surface of the third material. In some aspects, the methods comprise disposing a third auxiliary layer at at least a portion of the second surface of the third material.
In some methods, the third auxiliary layer present on the second surface of the third material can be the same or different as the third auxiliary layer present on the first surface of the third material. Yet, in still further aspects, each of the first, second or third auxiliary layers can be the same or different.
Also disclosed are methods where the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises a resorbable material, a non-resorbable material, or a combination thereof. Yet, in other methods, the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers selected from polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyamide, polyethylene, terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA) or a combination thereof or natural/regenerated fibers selected from cotton, silk, linen, cellulose acetate, collagen, or a combination thereof.
While in other aspects, the first, second, and/or third auxiliary layer configured to impart to at least a portion of the first, second, and/or third material hydrophobic or hydrophilic properties, elastomeric properties, mechanical resilience, adhesive properties, tissue-in-growth inhibition, or any combination thereof.
In certain methods, the first, second, and/or third auxiliary layer comprises a resorbable material, a non-resorbable material, or a combination thereof. Yet, in other methods, the first, second, and/or third auxiliary layer comprises one or more thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, or polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), polyamide, polyethylene, terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA).
Also disclosed are aspects directed to the methods comprising disposing the first material between two layers of the first perforated material, and wherein the two layers of the first perforated material are at least partially coupled to each other.
One aspect is directed to the methods comprising the second material disposed between two layers of the second perforated material and wherein the two layers of the second perforated material are at least partially coupled to each other. While another aspect is directed to the methods comprising disposing the third material between two layers of the third perforated material; and wherein at the two layers of the third perforated material are at least partially coupled to each other.
In some methods, at least a portion of the second surface of the first material is disposed on the first surface of the first perforated material. While in other methods, at least a portion of the first surface of the first material is disposed on the second surface of the first perforated material. In still further methods, at least a portion of the second surface of the second material is disposed on the first surface of the second perforated material.
In some aspects disclosed are methods, at least a portion of the first surface of the second material is disposed on the second surface of the second perforated material. In yet other aspects, at least a portion of the second surface of the third material can be disposed on the first surface of the third perforated material.
In still further methods, at least a portion of the first surface of the third material is disposed on the second surface of the third perforated material.
In some methods, at least a portion of the first auxiliary layer and at least a portion of the first perforated material are coupled to each other. In yet further methods, at least a portion of the second auxiliary layer and at least a portion of the second perforated material are coupled to each other. And in still further methods, at least a portion of the third auxiliary layer and at least a portion of the third perforated material are coupled to each other.
Additional aspects of the disclosure will be set forth, in part, in the detailed description, figures, and claims which follow, and in part will be derived from the detailed description or can be learned by practice of the disclosure. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure as disclosed.
Various aspects are depicted in the accompanying drawings for illustrative purposes and should in no way be interpreted as limiting the scope of the disclosures. In addition, various features of different disclosed aspects can be combined to form additional aspects, which are part of this disclosure. Throughout the drawings, reference numbers may be reused to indicate correspondence between reference elements. However, it should be understood that the use of similar reference numbers in connection with multiple drawings does not necessarily imply a similarity between respective aspects associated therewith. Furthermore, it should be understood that the features of the respective drawings are not necessarily drawn to scale, and the illustrated sizes thereof are presented for the purpose of illustration of inventive aspects thereof. Generally, certain of the illustrated features may be relatively smaller than as illustrated in some aspects or configurations.
The present disclosure can be understood more readily by reference to the following detailed description, examples, drawings, and claims, and their previous and following description. However, before the present articles, systems, and/or methods are disclosed and described, it is to be understood that this disclosure is not limited to the specific or exemplary aspects of articles, systems, and/or methods disclosed unless otherwise specified, as such can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.
The following description of the disclosure is provided as an enabling teaching of the disclosure in its best, currently known aspect. To this end, those skilled in the relevant art will recognize and appreciate that many changes can be made to the various aspects of the disclosure described herein while still obtaining the beneficial results of the present disclosure. It will also be apparent that some of the desired benefits of the present disclosure can be obtained by selecting some of the features of the present disclosure without utilizing other features. Accordingly, those of ordinary skill in the pertinent art will recognize that many modifications and adaptations to the present disclosure are possible and may even be desirable in certain circumstances and are a part of the present disclosure. Thus, the following description is again provided as illustrative of the principles of the present disclosure and not in limitation thereof.
As used in this application and in the claims, the singular forms “a,” “an,” and “the” include the plural forms unless the context clearly dictates otherwise. Thus, for example, a reference to a “material” includes aspects having two or more such materials unless the context clearly indicates otherwise.
It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. As used in the specification and in the claims, the term “comprising” can include the aspects “consisting of” and “consisting essentially of.” Additionally, the term “includes” means “comprises.”
For the terms “for example,” “exemplary,” and “such as,” and grammatical equivalences thereof, the phrase “and without limitation” is understood to follow unless explicitly stated otherwise.
Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint. Unless stated otherwise, the term “about” means within 5% (e.g., within 2% or 1%) of the particular value modified by the term “about.”
Throughout this disclosure, various aspects of the disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, 6 and any whole and partial increments therebetween. This applies regardless of the breadth of the range.
As used herein, the term “composition” is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from a combination of the specified ingredients in the specified amounts.
A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included. As used herein, the terms “optional” or “optionally” mean that the subsequently described event or circumstance may or may not occur and that the description includes instances where said event or circumstance occurs and instances where it does not.
It will be understood that when an element is referred to as being “connected” or “coupled” to another element, it can be directly connected or coupled to the other element, or intervening elements may be present. In contrast, when an element is referred to as being “directly connected” or “directly coupled” to another element, there are no intervening elements present. Other words used to describe the relationship between elements or layers should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” “on” versus “directly on”).
As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.
It will be understood that, although the terms “first,” “second,” etc., may be used herein to describe various elements, components, regions, layers and/or sections. These elements, components, regions, layers, and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer, or section from another element, component, region, layer, or a section. Thus, a first element, component, region, layer, or section discussed below could be termed a second element, component, region, layer, or section without departing from the teachings of example aspects.
Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein interpreted accordingly.
The terms “fiber” and “material comprising a plurality of fibers” are used herein according to their broad and ordinary meanings and may refer to any type of natural or synthetic substance or material that is significantly longer than it is wide, including any elongate or relatively fine, slender, and/or threadlike piece, filament, cord, yarn, plie, strand, line, string, or portion thereof. Furthermore, “fiber” or “material comprising a plurality of fibers” can refer to a single filament or collectively to a plurality of filaments. Examples of material comprising a plurality of fibers in accordance with aspects of the present disclosure include, but are not limited to, any type of cloth, fabric, or textile. It is understood that in certain unlimiting aspects, the term “material comprising a plurality of fibers” can refer to cloth, fabric, textile, or interlocking-fiber material that can cover or form certain features of the disclosed devices.
As used herein, the term “polyester” refers to a category of polymers that contain the ester functional group in their main chain. Polyesters disclosed herein include naturally occurring chemicals, such as in the cutin of plant cuticles, as well as synthetics produced through step-growth polymerization. In certain examples, the polyesters comprise polyethylene terephthalate (PET) homopolymer and copolymers, polypropylene terephthalate (PPT) homopolymer and copolymers and polybutylene terephthalate (PBT) homopolymer and copolymers, and the like, including those that contain comonomers such as cyclohexane dimethanol, cyclohexane dicarboxylic acid, isophthalic acid, and the like.
The term “polyamide,” as utilized herein, is defined to be any long-chain polymer in which the linking functional groups are amide (—CO—NH—) linkages. The term polyamide is further defined to include copolymers, terpolymers, and the like, as well as homopolymers and also includes blends of two or more polyamides. In some aspects, the plurality of polyamide fibers comprise one or more of nylon 6, nylon 66, nylon 10, nylon 612, nylon 12, nylon 11, or any combination thereof. In other aspects, the plurality of polyamide fibers comprise nylon 6 or nylon 66. In yet other aspects, the plurality of polyamide fibers are nylon 6. In a yet further aspect, the plurality of polyamide fibers are nylon 66.
As defined herein, the term “polyolefin” refers to any class of polymers produced from a simple olefin (also called an alkene with the general formula CnH2n) as a monomer. In some aspects, the polyolefins include but are not limited to polyethylene, polypropylene, both homopolymer and copolymers, poly(I-butene), poly(3-methyl-1-butene), poly(4-methyl-1-pentene) and the like, as well as combinations or mixtures of two or more of the foregoing.
As defined herein, the term “polyurethane” refers to any class of polymers composed of a chain of organic units joined by carbamate (urethane, R1—O—CO—NR2—R3, wherein R1, R2 and R3 are the same or different) links.
As defined herein, the term “polyether” refers to any class of polymers composed of a chain of organic units joined by an ether group.
As defined herein, the term “polyurea” refers to any class of polymers where alternative monomer units of isocyanates and amines react with each other to form urea linkages.
As used herein, the term “substantially” means that the subsequently described event or circumstance completely occurs or that the subsequently described event or circumstance generally, typically, or approximately occurs.
Still further, the term “substantially” can in some aspects refer to at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% of the stated property, component, composition, or other condition for which substantially is used to characterize or otherwise quantify an amount.
As used herein, the term “substantially,” in, for example, the context “substantially identical” or “substantially similar” refers to a method or a system, or a component that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% by similar to the method, system, or the component it is compared to.
Although the operations of exemplary aspects of the disclosed method may be described in a particular, sequential order for convenient presentation, it should be understood that disclosed aspects can encompass an order of operations other than the particular, sequential order disclosed. For example, operations described sequentially may, in some cases, be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular aspect are not limited to that aspect and may be applied to any aspect disclosed.
Moreover, for the sake of simplicity, the attached figures may not show the various ways (readily discernable, based on this disclosure, by one of ordinary skill in the art) in which the disclosed system, method, and apparatus can be used in combination with other systems, methods, and apparatuses. Additionally, the description sometimes uses terms such as “produce” and “provide” to describe the disclosed method. These terms are high-level abstractions of the actual operations that can be performed. The actual operations that correspond to these terms can vary depending on the particular implementation and are, based on this disclosure, readily discernible by one of ordinary skill in the art.
Aspects of the technology disclosed herein are directed to implantable prosthetic devices and various components of such devices. More specifically, some of the aspects related to implantable prosthetic valves.
It is understood that commonly many components of the medical devices can be covered, at least partially, with materials comprising a plurality of fibers or fibrous materials. Examples of medical device components that can be covered or otherwise associated with a cloth or other materials comprising fibers include certain stents, which can generally comprise a conduit form configured to be placed in a body to create or maintain a passageway within the body or to provide a relatively stable anchoring structure for supporting one or more other devices or anatomy. At least partially cloth-covered stents can be used for a variety of purposes, such as for expansion of certain vessels, including blood vessels, ducts, or other conduits, whether vascular, coronary, biliary, or other types. In the context of prosthetic heart valve devices, a stent can serve as a structural component for anchoring the prosthetic heart valve to the tissue of a heart valve annulus. Such a stent can have varying shapes and/or diameters.
It should be understood that prosthetic heart valve implants, as well as many other types of prosthetic implant devices and other types of devices, can include various cloth-covered components and/or portions. For example, a sealing portion of a medical implant device, such as a prosthetic heart valve skirt component/portion, can be sutured to a frame thereof to help prevent blood from leaking around the outer edges or circumference of the device.
In some implementations, cloth coverings for medical device components can be secured using sutures. For example, in some implementations, a human operator may handle and execute sutures on implant device components to secure a cloth thereto. However, the execution of sutures by a human operator may be relatively difficult and/or cumbersome in certain situations. For example, where small stitches are to be made with relatively high precision, the complexity and/or associated operator burden may result in injury/strain and/or undesirably-low product quality. Furthermore, medical implant devices, such as certain heart valve implant devices, may require upward of a thousand sutures, or more, which can involve substantially labor-intensive and error-susceptible suturing procedures. Therefore, reducing the collaborative human involvement in the application of fibrous material to medical device components can be desirable to improve quality and efficiency and/or to reduce operator strain.
Certain aspects disclosed herein provide for the implantable prosthetic devices that can comprise materials comprising a plurality of fibers comprising an electrospun silk. Even further disclosed herein are aspects where these materials and devices are formed using electrospinning devices, systems, processes, and mechanisms. Examples of medical implant devices and heart valve structures that may be applicable to certain aspects presented herein are disclosed in WIPO Publication No. WO 2015/070249, the entire contents of which are hereby expressly incorporated by reference for all purposes.
The aspects disclosed below include materials comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises an electrospun silk. Such materials, as disclosed in detail below, can be formed by electrospinning processes. Electrospinning processes generally employ high voltages to create an electric field between a droplet of polymer solution at the tip of a needle and a collector plate, as described in detail below. In certain aspects, one electrode of the voltage source can be placed into the solution, and the other is connected to the collector. This creates an electrostatic force. As the voltage is increased, the electric field intensifies, causing a force to build-up on the pendant drop of polymer solution at the tip of the needle. This force acts in a direction opposing the surface tension of the drop. The increasing electrostatic force causes the drop to elongate, forming a conical shape. When the electrostatic force overcomes the surface tension of the drop, a charged, continuous jet of a solution is ejected from the cone. The jet of solution accelerates towards the collector, whipping and bending wildly. As the solution moves away from the needle and toward the collector, the jet rapidly thins and dries as the solvent evaporates. On the surface of the grounded collector, a nonwoven mat of randomly oriented solid nanofibers is deposited. Certain methods, devices, and systems relating to electrospinning concepts that may be applicable to aspects of the present disclosure are disclosed in U.S. Publication No. 2017/0325976, the disclosure of which is hereby incorporated by reference in its entirety. The specific aspects of the methods are also disclosed below in more detail.
The aspects disclosed herein are related to materials comprising a plurality of electrospun silk fibers. To electrospun fibers, often and as described in detail below, a natural protein, silk fibroin (SF), can be utilized. SF derived from silkworm plays a crucial role in biomedical applications and tissue engineering (W. H. Zhou et al., ACS Appl. Mater. Inter. 9 (2017), 25830-25846; J. Du et al., App. Surf. Sci., 447 (2018), 269-278). Silkworm is mainly composed of silk fibroin coated with sericin, and their content is over 95%. It was found that there is a small amount of carbohydrates and other impurities in silkworms can be present. SF structure is mainly composed of glycine (46%), alanine (29%), serine (18%), and other 18 kinds of amino acids (J. Brown et al., Acta Biomater. 11 (2015), 212-221). SF consists of a light (L) chain polypeptide and a heavy (H) chain polypeptide linked together via a single disulfide bond at the C-terminus of the H-chain, forming an H-L complex (I.D. Koh et al., Prog. Polym. Sci. 46 (2015), 86-110). SF is considered to be one of the biological materials with the most applicative prospect due to the unique properties of excellent biocompatibility (Y. F. Feng et al., ACS Sustain. Chem. Eng. 5 (2017), 6227-6236), control of excellent mechanical properties (F. Teule et al., Proc. Natl. Acad. Sci. U.S.A. 109 (1012) 923-928), biodegradability (A. Teimouri et al., Polym. Degrad. Stabil. 121 (2015), 18-29; F. M. Miroiu et al., Appl. Surf. Sci. 355 (2015), 1123-1131) hemocompatibility, cytocompatibility and its interactions with cells.
In the aspects disclosed herein, silk fibroin was found to be a good alternative to the previously disclosed materials and textiles used in the implantable prosthetic devices. It was shown that the use of the silk fibroin as a source of the fibrous material allows controlling the rate of degradation of the formed components as an important feature of function tissue design. Without wishing to be bound by any theory, it was assumed that the use of the silk-fibroin as a source for electrospun silk allows successfully matching the rate of scaffold degradation to the rate of tissue growth.
Aspects disclosed herein include an implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; a leaflet structure positioned within the frame; an inner skirt positioned along the inner surface of the frame; at least one outer skirt positioned around the outer surface of the frame; wherein at least a portion of one of the leaflet structure, the inner skirt, or the at least one outer skirt comprises a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises an electrospun silk; and wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration.
It is further understood that also disclosed herein are aspects of an implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; a leaflet structure positioned within the frame and at least one outer skirt positioned around the outer surface of the frame; wherein at least a portion of one of the leaflet structure, or the at least one outer skirt comprises a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises an electrospun silk; and wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration. In such aspects, the inner skirt does not have to be present in the disclosed implantable prosthetic device. However, disclosed are the aspects where the inner skirt is also present. It is further understood that all other materials that can be present in the leaflet structure and/or outer skirt can be any of the materials disclosed below.
Also disclosed herein are aspects of an implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; a leaflet structure positioned within the frame and an inner skirt positioned around the inner surface of the frame; wherein at least a portion of one of the leaflet structure, or the inner skirt comprises a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises an electrospun silk; and wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration. In such aspects, the outer skirt does not have to be present in the disclosed implantable prosthetic device. However, disclosed are the aspects where the outer skirt is also present. It is further understood that ail other materials that can be present in the leaflet structure and/or inner skirt can be any of the materials disclosed below.
Also disclosed aspects include an implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; wherein at least one of the following components is also present: a leaflet structure positioned within the frame; an inner skirt positioned along the inner surface of the frame; at least one outer skirt positioned around the outer surface of the frame; where when the at least one of the disclosed components is present at least a portion of these components comprises a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; and wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration. It is understood that in these specific aspects, the leaflet structure may or may not be present, or the inner skirt may or may not be present, or at least one outer skirt may or may not be present. It is further understood that all other materials that can be present in either the leaflet structure, and/or inner skirt, and/or outer skirt can be any of the materials disclosed below.
In some disclosed aspects, the implantable prosthetic device can comprise an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end.
The frame 110 can be at least partially self-expanding and/or maybe mechanically expandable (e.g., balloon-expandable). For example, a self-expanding frame of the stent can be crimped or otherwise compressed into a small tube and may possess sufficient elasticity to spring outward by itself when a restraint, such as an outer sheath/catheter, is removed. In contrast, a balloon-expanding stent may comprise a material that is relatively less elastic and is capable of plastic expansion from the inside-out when converting the stent from a contracted diameter/configuration to an expanded diameter/configuration.
The plastic expansion may be accomplished with a balloon or other device, such as a device with mechanical fingers. With such balloon-expanding stents, the stent frame may plastically deform after the application of a deformation force, such as an inflating balloon or expanding mechanical fingers.
The frame 110 of a stent (e.g., self-expanding stent or balloon-expanding stent) may be used as part of a prosthetic heart valve having single-stage implantation in which a surgeon secures a heart valve having a fibrous anchoring skirt and valve member to a heart valve annulus as one unit or piece. Certain stent solutions for aortic valve replacement in accordance with some aspects of the present disclosure are disclosed in U.S. Pat. No. 8,641,757, which is incorporated herein by reference in its entirety. In some implementations, an exemplary delivery system advances the valve implant device with the stent at the leading or distal end until it is located within the valve annulus and/or left ventricular outflow tract, at which point a balloon can inflate to expand the stent against the aortic annulus and/or ventricular tissue.
As shown in
In the illustrated aspect, pairs of adjacent circumferential struts in the same row are connected to each other by a respective, generally U-shaped crown structure or portion 126. The crown structures 126 can each include a horizontal portion extending between and connecting the adjacent ends of the struts such that a gap is defined between the adjacent ends and the crown structure connects the adjacent ends at a location offset from the strut's natural point of intersection. The crown structures 126 can significantly reduce residual strains on the frame 110 at the location of the struts 120, 122, 124 during crimping and expanding of the frame 110. Each pair of struts 122 connected at a common crown structure 126 can generally form a cell with an adjacent pair of struts 124 in the row above. Each cell can be connected to an adjacent cell at node 132. Each node 132 can be interconnected with the lower row of struts by a respective vertical (axial) strut 130 that is connected to and extends between a respective node 132 and a location on the lower row of struts 120 where two struts are connected at their ends opposite of a crown structure 126.
In certain aspects, lower struts 120 have a greater thickness or diameter than upper struts 122, 124. In one implementation, for example, lower struts 120 have a thickness of about 0.42 mm and upper struts 122, 124 have a thickness of about 0.38 mm. In the particular aspect of
In still further aspects, the implantable device as disclosed herein comprises a leaflet structure positioned with the frame, and/or an inner skirt positioned along the inner surface of the frame and/or at least one outer skirt positioned around the outer surface of the frame. As disclosed herein, at least a portion of one of the leaflet structure, the inner skirt, or the at least one outer skirt comprises a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk. However, it is further understood that in certain aspects, any or ail of the disclosed components can comprise the material comprising the plurality of electrospun silk fibers.
In certain aspects, when at least a portion, or a whole surface, of the inner skirt comprises the material comprising the plurality of fibers comprising the electrospun silk, the material is referred to as a first material. While in other aspects, when at least a portion, or a whole surface, of the outer skirt comprises the material comprising the plurality of fibers comprising the electrospun silk, the material is referred to as a second material. While in still further aspects, when at least a portion, or a whole surface, of the leaflet structure comprises the material comprising the plurality of fibers comprising the electrospun silk, the material is referred to as a third material. It is understood that these definitions are used to distinguish between the materials of each component and do not indicate a specific order or specific material. It is understood, as described below, that the first material, the second material, and/or the third material can be the same or different.
It is further understood, and as it is described below, each or all of the materials comprising electrospun silk can be engineered to have specific properties depending on the desired application. For example, a fibrous material (the third material as disclosed herein) used to form the leaflet structure is designed to exhibit properties that are different from the properties required for the material used for the inner (the first material) or outer skirt (the second material) of the implantable device. Therefore, described herein are the aspects where the first, second, and third materials are the same as well the aspects where the first, second, and third materials are different.
Exemplary and unlimiting implantable prosthetic devices having various components are shown in
In still further aspects, and as discussed in detail below, the leaflet structure 364 can be formed by the electrospinning methods. In certain aspects, the third material comprising the leaflet structure can be formed by electrospinning of the silk fibroin fibers, for example, on the third predetermined mandrel. In such aspects, the third predetermined mandrel can have a form of the desired leaflet structure (for example,
Similarly, the inner skirt 301 can be formed by direct electrospinning as discussed in detail below, or it can be prepared from the sheet of the first material, cut to the desired form, and then, is attached to the frame by any known in the art methods. For example, it can be attached to the inner surface of the frame with a fastener. In certain aspects, the fastener can comprise glue and/or sutures.
The valve implant device 300 can be suitable for implantation in the annulus of a native aortic valve, for example, but also can be adapted to be implanted in other native valve annuluses of the heart or various other ducts or orifices of the body. The valve implant device 300 has an inflow end 380 and an outflow end 382.
The valve implant device 300 and stent frame 310 as disclosed herein are configured to be radially collapsible to a collapsed or crimped state for introduction into the body within a delivery catheter and radially expandable to an expanded state for implanting the valve 300 at a desired location in the body (e.g., the native aortic valve). For example, and without limitation, the stent frame 310 can be made of a plastically-expandable material that permits crimping of the valve to a smaller profile for delivery and expansion of the valve using an expansion device, such as the balloon of a balloon catheter. Alternatively, the valve implant device 300 can be a self-expanding valve, wherein the frame is made of a self-expanding material such as memory metal (e.g., Nitinol). A self-expanding valve can be crimped to a smaller profile and held in the crimped state with a restraining device, such as a sheath covering the valve. When the valve is positioned at or near the target site, the restraining device may be removed to allow the valve to self-expand to its expanded, functional size. It is further understood, however, that other suitable for this purpose materials can also be employed to form the frame.
Other exemplary aspects of implantable medical devices are shown in
Frame 1200 can be made from any of various biocompatible materials, such as stainless steel or a nickel-titanium alloy (“NiTi”), for example, Nitinol. With reference to
The lattice struts 26 can be pivotably coupled to one another. In the illustrated aspect, for example, the end portions of the struts 26 forming the apices 28 at the outflow end 18 and at the inflow end 16 of the frame can have a respective opening 32. The struts 26 also can be formed with apertures 34 located between the opposite ends of the struts. Respective hinges can be formed at the apices 28 and at the locations where struts 26 overlap each other between the ends of the frame via fasteners 36, which can comprise rivets or pins that extend through the apertures 32, 34. The hinges can allow the struts 26 to pivot relative to one another as frame 1200 is expanded or contracted, such as during assembly, preparation, or implantation of the prosthetic valve 10. For example, frame 1200 (and, thus, the prosthetic valve 10) can be manipulated into a radially compressed or contracted configuration, coupled to a delivery apparatus, and inserted into a subject for implantation. Once inside the body, the prosthetic valve 10 can be manipulated into an expanded state and then released from the delivery apparatus. Additional details regarding frame 1200, the delivery apparatus, and devices and techniques for radially expanding and collapsing the frame can be found in U.S. Publication No. 2018/0153689, which is incorporated herein by reference. Additional details about such an exemplary prosthetic valve can also be found in U.S. Publication No. 2019/0046314, which is incorporated herein by reference.
As further illustrated in
The outer skirt 30 can be configured to establish a seal with the native tissue at the treatment site to reduce or prevent paravalvular leakage. The outer skirt 30 can include a main body portion 38 disposed about an outer circumference of the frame 1200. The outer skirt 30 can be secured to the frame by direct electrospinning, as discussed in detail below and show, for example, in
Also disclosed herein are the aspects where each fiber of the plurality of fibers present in the first material and/or the second material and/or third material have first extending direction and a plurality of undulation. In yet further aspects, the first extending direction can comprise a circumferential direction, a radial direction, or a combination thereof. While in other aspects, the plurality of undulations are present in the collapsed configuration. In still further aspects, the plurality of undulations are configured to straighten when the implantable prosthetic valve is in the expanded configuration. Such exemplary aspects are shown in
As disclosed above, in certain aspects, to improve adhesion between the frame and the components electrospun on or attached thereto, an adhesive material can be disposed between at least a portion of the annular frame and at least a portion of the outer skirt and/or between at least a portion of the annular frame and at least a portion of the inner skirt. As in any of the disclosed above aspects, at least a portion of the inner skirt can be attached to the annular frame by direct electrospinning of the plurality of fibers on at least a portion of the inner surface of the annular frame. While in other aspects, the inner skirt material can be formed by the electrospinning from silk fibroin solution to form a sheet of the material comprising electrospun silk from which the inner skirt can be cut out by any known in the art methods (for example, such as laser cutting or ultrasonic cutting) and attached to the frame. Similarly, there are also aspects where at least a portion of the outer skirt is attached to at least a portion of the annular frame by direct electrospinning of the plurality of fibers on at least a portion of the outer surface of the annular frame. While in other aspects, the outer skirt material can also be formed by the electrospinning from silk fibroin solution to form a sheet of the material comprising electrospun silk from which the outer skirt can be cut out by any known in the art methods (for example, such as laser cutting or ultrasonic cutting) and attached to the frame.
In yet further aspects, at least a portion of the plurality of fibers has a random orientation. While in other aspects, at least a portion of the plurality of fibers has a predetermined aligned orientation. In yet further aspects, the first and/or the second and the third/material can comprise at least a portion of the plurality of fibers have a random orientation, and at least a portion of the plurality of fibers have a predetermined aligned orientation. In such exemplary aspects, the orientation of the fibers or the lack thereof can be controlled by various parameters of the electrospinning procedures, as disclosed below.
In certain aspects, to control and/or alter mechanical properties of the first and/or the second and/or the third material, additional fibers can be present in these materials. For example, the plurality of fibers can comprise a resorbable material, non-resorbable material, or a combination thereof. For example, in certain aspects, to achieve desired mechanical properties, the plurality of fibers can further comprise thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof. In certain aspects, where only bioresorbable and biocompatible fibers are desired, the plurality of fibers can comprise polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof. In aspects where the final component is not desired to be bioresorbable, other fibers can be present. For example, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), or a combination thereof. It is understood that any know variation of the PET can be used, such for example, and without limitation, high tenacity PET can also be utilized.
In certain exemplary and unlimiting aspects, and depending on the desired applications, at least a portion of the plurality of fibers can comprise a bicomponent fiber. It is understood that any known in the art configurations of the bicomponent fibers can be utilized. For example, and without limitation, the bicomponent fiber can comprise a side-by-side configuration, a sheath-core configuration, an islands-in-the-sea configuration, a tri-lobal, a segmented pie configuration, or any combination thereof. In still further exemplary aspects, the bicomponent fiber comprises the sheath-core configuration. In some aspects, a sheath and/or core can comprise a resorbable material, a non-resorbable material, or a combination thereof. In certain aspects, a sheath of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof. While is still further exemplary aspects, a sheath of the bicomponent fiber can comprise silk, while a core of the bicomponent fiber can comprise one or more of thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
In still further aspects, the plurality of fibers can have an average diameter from about 3 nm to about 15,000 nm, including exemplary values of about 5 nm, about 10 nm, about 15 nm, about 20 nm, about 25 nm, about 30 nm, about 35 nm, about 40 nm, about 45 nm, about 50 nm, about 55 nm, about 60 nm, about 65 nm, about 70 nm, about 75 nm, about 80 nm, about 85 nm, about 90 nm, about 95 nm, about 100 nm, about 150 nm, about 200 nm, about 300 nm, about 400 nm, about 500 nm, about 600 nm, about 700 nm, about 800 nm, about 900 nm, about 1,000 nm about 1,200 nm, about 1,500 nm, about 2,000 nm, about 2,500 nm, about 3,000 nm, about 3,500 nm, about 4,000 nm, about 4,500 nm, about 5,000 nm, about 5,500 nm, about 6,000 nm, about 6,500 nm, about 7,000 nm, about 7,500 nm, about 8,000 nm, about 8,500 nm, about 9,000 nm, about 9,500 nm, about 10,000 nm, about 10,500 nm, about 11,000 nm, about 11,500 nm, about 12,000 nm, about 12,500 nm, about 12,000 nm, about 12,500 nm, about 13,000 nm, about 13,500 nm, about 14,000 nm, and about 13,400 nm. It is understood that the plurality of fibers can have an average diameter having values between any two foregoing values. It is further understood that the average diameter of the fiber can be controlled by electrospinning parameters, as discussed in detail below.
In still further aspects, wherein the first material, and/or the second material, and/or the third material can have a thickness from about 0.1 m to about 2 mm, including exemplary values of about 0.2 m, about 0.5 m, about 1 m, 5 m, about 10 m, about m, about 20 m, about 30 m, about 50 m, about 100 m, about 200 m, about 300 m, about 400 m, about 500 m, about 600 m, about 700 m, about 800 m, about 900 m, about 1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 μm, about 1.6 mm, about 1.7 mm, about 1.7 mm, and about 1.9 mm. Still further, the thickness can be any thickness between any two foregoing values. Again, it is further understood that the thickness of the material can be controlled by varying the parameters of the electrospinning process.
In still further aspects, at least a portion of the first material, and/or the second material, and/or third material exhibits porosity. It is understood that, as referenced herein, the term “pore size” refers to the mean size of the nanofiber pores. As used herein, porosity is determined by a ratio of pores to a unit of volume. Again, it is understood that the level of porosity and/or pore size can be controlled by varying the parameters of the electrospinning process. In exemplary aspects disclosed herein, the at least a portion of the first material, and/or the second material, and/or third material can have an average pore size from about 100 nm to about 100 μm, including exemplary values of about 150 nm, about 200 nm, about 300 nm, about 400 nm, about 500 nm, about 600 nm, about 700 nm, about 800 nm, about 900 nm, about 1,000 nm about 1,200 nm, about 1,500 nm, about 2,000 nm, about 2,500 nm, about 3,000 nm, about 3,500 nm, about 4,000 nm, about 4,500 nm, about 5,000 nm, about 5,500 nm, about 6,000 nm, about 6,500 nm, about 7,000 nm, about 7,500 nm, about 8,000 nm, about 8,500 nm, about 9,000 nm, about 9,500 nm, about 1 μm, about 1.5 μm, about 2 μm, about 2.5 prn, about 3 μm, about 3.5 μm, about 4 μm, about 4.5 μm, about 5 μm, about 10 μm, about 15 μm, about 20 μm, about 30 prn, about 40 prn, about 50 μm, about 60 μm, about 70 μm, about 80 μm, and about 90 μm. Still further, the porosity can have any value between any two foregoing values.
Exemplary materials having various average fiber diameter and porosity are shown in
Also disclosed herein are aspects where the first material and/or the second material, and/or third material comprise a plurality of layers, wherein each of the plurality of layers comprises electrospun silk, and wherein each of the plurality of layers is disposed on each other. It is understood that the number of layers can be any number that provides for the desired material. In such exemplary aspects, at least a first portion of the plurality of layers can have a surface area that is substantially smaller than a surface area of a second portion of the plurality of layers' surface area. It is understood that such different portions of the layers can be formed by varying electrospinning parameters during the electrospinning process. The electrospinning parameters can include the distance between the spinneret and the collection substrate, the amount of the voltage applied used during electrospinning, extrusion rate, a spinning rate of the collection substrate if it rotates, and the like. For example, some portions of the materials can be more porous than others and thus have a higher surface area than other portions of the materials. In certain exemplary and unlimiting aspects, if substantially no tissue growth is desired, the portions of some of the layers can be constructed to be very dense, less porous, and provide a substantially smooth surface. While in other aspects, where extensive tissue growth is desired, the portions of the layers can have higher porosity and less dense. It is understood again that pore size and, therefore, a surface area can be regulated by varying various electrospinning process parameters.
Also, as disclosed above, various components of the implantable device can have different desired properties. For example, the inner skirt or the leaflet structure of the device may not need to be susceptible to excessive growth or to be rapidly bioresorbable. In such aspects, denser, less porous materials can be utilized. Also, in such aspects, any of the additional fibers, as disclosed above, can be present in the plurality of fibers to increase the mechanical strengths of the materials and regulate bioresorbability and/or biodegradation as desired.
Also disclosed herein are aspects where the first material and/or the second material and/or the third material can comprise various layers comprising a various plurality of fibers. For example, and without limitation, in certain aspects, any of the disclosed materials can have a plurality of layers having different fiber compositions. In some exemplary and unlimiting aspects, the material can have a plurality of layers comprising electrospun silk followed by a plurality of layer comprising electrospun silk and any of the disclosed above polymers, followed by a plurality of layers comprising any of the disclosed above electrospun polymers without the presence of the electrospun silk and so on. Again, it is understood that the described sequence of the plurality of layers is only exemplary, and any or none of the disclosed layers can be present.
For example, at least a portion of the inner skirt further can comprise a first perforated material having a first surface facing the annular frame and an opposite second surface and wherein the first material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the first perforated material. Yet in another example, at least a portion of the outer skirt further can comprise a second perforated material having a first surface facing the annular frame and an opposite second surface and wherein the second material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the second perforated material. Yet still, in another example, at least a portion of the leaflet structure can comprise a third perforated material having a first surface facing the annular frame and an opposite second surface and wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the third perforated material.
Also disclosed are examples where at least a portion of the first surface of the first material comprises a first auxiliary layer and/or wherein at least a portion of the second surface of the first material comprises a first auxiliary layer. In such exemplary aspects, the first auxiliary layer present on the second surface of the first material is the same or different as the first auxiliary layer present on the first surface of the first material.
Also disclosed are examples where at least a portion of the first surface of the second material comprises a second auxiliary layer and/or wherein at least a portion of the second surface of the second material comprises a second auxiliary layer. In such exemplary aspects, the second auxiliary layer present on the second surface of the second material is the same or different as the second auxiliary layer present on the first surface of the second material.
Still further are also disclosed examples where at least a portion of the first surface of the third material comprises a third auxiliary layer and/or wherein at least a portion of the second surface of the third material comprises a third auxiliary layer. In such exemplary and unlimiting aspects, the third auxiliary layer present on the second surface of the third material is the same or different as the third auxiliary layer present on the first surface of the third material.
In still further aspects and as shown in
Some exemplary and unlimiting configurations are further shown in
In still further aspects, additional configurations can be considered. For example, as shown in
In still further aspects and as shown in
In some aspects, any of the perforated materials can comprise a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers comprising resorbable or non-resorbable materials, or a combination thereof. In still further aspects, the biocompatible polymers can be selected from polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA) or a combination thereof or natural/regenerated fibers selected from cotton, silk, linen, cellulose acetate, collagen, or a combination thereof. It is understood that the degree of perforation can be adjusted depending on the desired performance of the final materials.
In yet other aspects, any of the auxiliary layers can comprise one or more thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, or polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA). It is understood that any of the auxiliary layers can comprise resorbable materials, non-resorbable materials, or any combination thereof.
It is understood that in some aspects, the first material can comprise the disclosed herein electrospun fibers and at least one perforated material and/or at least one auxiliary layer. In yet further aspects, the second material can comprise the disclosed herein electrospun fibers and at least one perforated material and/or at least one auxiliary layer. While in still further aspects, the third material can comprise the disclosed herein electrospun fibers and at least one perforated material and/or at least one auxiliary layer. It is also understood that in some aspects, some of the materials comprise all the layers, while in other aspects, some of the materials comprise only some of the layers. It is also understood that the combination of all of the layers can be found in any or all of the first, second, and third materials.
In still further aspects, the presence of the perforated material can provide mechanical property enhancement of nanofibers while utilizing the benefits from the nanofiber structure y exposing these fibers through the porous structure.
In other aspects, any of the disclosed herein auxiliary layer s are configured to impart to at least a portion of the first, second, and/or third material hydrophobic or hydrophilic properties, elastomeric properties, mechanical resilience, adhesive properties, tissue-in-growth inhibition, or any combination thereof. It is understood that when for example, TPU or PU is used as an auxiliary layer at at least one portion of the inner and/or outer surface of the plurality of electrospun fibers, this portion will prohibit tissue in-growth while having increased mechanical properties.
In certain aspects, the first material and/or the second material, and/or third material can exhibit tensile strength from greater than 0 MPa to about 20 MPa, including the exemplary value of about 0.5 MPa, about 1 MPa, about 1.5 MPa, about 2 MPa, about 2.5 MPa, about 3 MPa, about 3.5 MPa, about 4 MPa, about 4.5 MPa, about 5 MPa, about 5.5 MPa, about 6 MPa, about 6.5 MPa, about 7.0 MPa, about 7.5 MPa, about 8 MPa, about 8.5 MPa, about 9.5 MPa, about 10 MPa, 10.5 MPa, about 11 MPa, about 11.5 MPa, about 12 MPa, about 12.5 MPa, about 13 MPa, about 13.5 MPa, about 14 MPa, about 14.5 MPa, about 15 MPa, about 15.5 MPa, about 16 MPa, about 16.5 MPa, about 17.0 MPa about 17.5 MPa, about 18 MPa, about 18.5 MPa, and about 19.5 MPa. Still further, the first material and/or the second material, and/or third material can exhibit tensile strength can have any value between any two foregoing values.
In certain aspects, the first material and/or the second material, and/or third material can exhibit elongation at break from greater than 0% to about 600%, including exemplary values of about 1%, about 10%, about 50%, about 100%, about 200%, about 300%, about 400%, and about 500%. Still further, the first material and/or the second material, and/or third material can exhibit elongation at break can have any value between any two foregoing values. Again it is understood that both for the tensile strength and elongation at break parameters, the skilled practitioner would choose the material having the desired properties for the specific application. For example, the first material used for the inner skirt may have properties that are different from the third material used to form the leaflet structure, and so on. It is further understood that such properties can be adjusted by changing electrospinning parameters, the average diameter of fibers, porosity, fiber composition, and the like.
In certain aspects, the first material and/or the second material, and/or third material can exhibit a water contact angle from about 0° to about 180°, including exemplary values of about 10°, about 20°, about 30°, about 40°, about 50°, about 60°, about 70°, about 80°, about 90°, about 100°, about 110°, about 120°, about 130°, about 140°, about 150°, about 160°, and about 170°. It is understood the first material and/or the second material, and/or third material can exhibit that any of the disclosed above water contact angles. It is further understood that the material having low contact angles are considered hydrophilic, and higher contact angles are considered hydrophobic. The hydrophilicity/hydrophobicity of the first material and/or the second material, and/or third material can be adjusted again by changing the density of the formed material and by chemical/physical treatment of the material to impart the desired properties to the materials. For example, hydrophobicity can be imparted to at least a portion of the fibers by exposing it to plasma. In such exemplary aspects, exposure to a 98% Helium+2% CF4 plasma or 99% Helium+1% CF4 gas plasma treatment can introduce hydrophobic groups such as fluorine groups on the fiber surfaces and to change their properties. In yet other exemplary aspects, hydrophilicity be imparted by treating the materials with 98% Helium+2% oxygen atmospheric pressure plasma. In such exemplary and unlimiting aspects, oxygen-free radicals can be formed. The oxygen-free radicals can attach themselves to fibers in the form of —CO—, —COOH, —COO—, —C═O, —O—COO groups and increase the hydrophilicity of a non-polar compound. In still further exemplary aspects, CH4 gas can cause a plasma polymerization of CH2 polymers capped with CHs end groups and change the hydrophilicity of the fibers. It is understood that the plasma treatments, as shown herein, are only exemplary, and both atmospheric pressure and vacuum-based plasma treatments can be used. In still further aspects, chemical treatments can also be utilized. In such exemplary aspects, the first and/or second and/or third materials can be treated with various chemical compounds to impart desired hydrophilic or hydrophobic properties. It is understood, however, that such treatments need to be compatible with the desired applications.
In still further aspects, various portions of the same material can have different properties. For example, and without limitation, the materials can be designed to have a change in various properties along the material's dimensions. The materials can also be designed to have different properties at the surface of the material and in the bulk of the material. Such variations in the properties can be gradual or steep, depending on the final application of the material. It is understood that the properties, such as fiber density, an average fiber diameter, a pore size, and pore density, and the like, can be varied by adjusting various process parameters of the electrospinning.
In still further aspects, by adjusting the composition of the plurality of fibers according to the aspects disclosed herein, the material can be designed to have various portions of bioresorbability or biodegradability or just degradability as desired.
In yet further aspects, the frame itself can also be plasma treated to improve the adsorption of the electrospun fibers disposed thereon.
Still further and as disclosed above, the first material and/or the second material, and/or third material can be at least partially biodegradable. While in other aspects, the first material and/or the second material, and/or third material are at least partially bioresorbable. While still in further aspects, and depending on the fibers' compositions, the first material and/or the second material, and/or third material can be at least partially degradable. Also disclosed herein are aspects where the first material and/or the second material, and/or third material are a scaffold material.
Also disclosed herein is an article comprising a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk, wherein the article has a collapsed configuration and an expanded configuration, and wherein the article is a part of an implantable device. In certain aspects, the article can be a paravalvular leak sealing article.
Paravalvular leak (PVL) is a complication associated with the implantation of a prosthetic heart valve. PVL refers to blood flowing through a channel between the structure of the implanted valve and cardiac tissue as a result of a lack of appropriate sealing. The majority of PVL are crescent, oval, or roundish-shaped, and their track can be parallel, perpendicular, or serpiginous. Transcatheter Heart Valve (THV) procedures generally use either a substantially inelastic woven cloth or a stretchable knitted cloth for PVL sealing.
When comparing the woven material with the knitted material for PVL sealing, the substantially inelastic woven material has the advantage of providing better dimensional stability that helps in procedures dealing with joining the valve components together using sutures and laser cutting of components. Further, the pore sizes and pore densities in a woven material can be engineered to balance sealing and tissue in-growth functions. On the other hand, knitted material provides better stretchability than woven cloth construction. Stretchability helps in reducing stress on a tissue to which the medical device comprising the fibrous material is attached.
With the next generation of THV frame designs that have changing frame dimensions, one of the requirements is to have the PVL seal material and/or the frame inner material to adapt to the changing frame dimensions. Thus, there is a need for a material having controlled stretchability and a lower profile to provide improved compliance by reducing potential stresses at locations where the cloth is secured to a bodily lumen. The present disclosure is describing the aspects of utilizing electrospun silk fibers addressing the issues disclosed above. As described above, the porosity, stretchability, the physical strength of the fibers can be controlled during the single manufacturing process by varying electrospinning parameters.
The paravalvular leak sealing article, as disclosed herein, can comprise any of the disclosed above inner skirts comprising a first material comprising a plurality of fibers comprising an electrospun silk. In such aspects, the inner skirt is configured to be positioned on at least a portion of an inner surface of an annular frame of the implantable prosthetic device. The paravalvular leak sealing article, as disclosed herein, can also comprise any of the disclosed herein outer skirts comprising a second material comprising a plurality of fibers comprising an electrospun silk. In such exemplary aspects, the outer skirt is configured to be positioned on at least a portion of an outer surface of an annular frame of the implantable prosthetic device.
The article can also comprise any of the disclosed herein leaflet structures comprising a third material comprising a plurality of fibers comprising an electrospun silk. In such aspects, the leaflet structure is configured to be positioned within at least a portion of an annular frame of the implantable prosthetic device. In still further aspects, the material can comprise any of the disclosed herein first materials, or the second materials, or the third materials, or any combination thereof.
The present disclosure also provides for methods of forming an implantable prosthetic valve. In such aspects, the methods can comprise: a) providing an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; b) forming an inner skirt comprising a first material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; c) forming an outer skirt comprising a second material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; d) attaching the inner skirt to at least a portion of the inner surface of the annular frame and attaching the outer skirt to at least a portion of the outer surface of the annular frame, wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration.
In certain aspects, the step of forming the inner skirt and the step of attaching the inner skirt occurs simultaneously. While in other aspects, the step of forming the inner skirt occurs prior to the step of attaching. In yet further aspects, the step of forming the outer skirt and the step of attaching the outer skirt occurs simultaneously. While in still further aspects, the step of forming the outer skirt occurs prior to the step of attaching. In certain aspects, the step of forming the inner skirt can occur before or after the step of forming the outer skirt. Similarly, the methods described herein can further comprise a step of positioning a leaflet structure comprising a third material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk within at least a portion of the annular frame. While it is also understood that the step of positioning the leaflet structure can occur before or after the step of forming the inner skirt and/or outer skirt.
The aspects disclosed herein described electrospinning methods to form the first and/or the second and/or the third materials.
In the aspects disclosed herein, the step of attaching the at least a portion of the first material to the at least a portion of the inner surface of the annular frame comprises directly electrospinning at least a portion of the plurality of fibers through at least one spinneret from a first solution comprising a first predetermined concentration of a silk fibroin at a predetermined extrusion rate. While in other aspects, the step of attaching the at least a portion of the second material to the at least a portion of the outer surface of the annular frame comprises directly electrospinning at least a portion of the plurality of fibers through at least one spinneret from a second solution comprising a second predetermined concentration of a silk fibroin at a predetermined extrusion rate.
Also disclosed are aspects where the first and/or the second materials are not formed directly on the annular frame but formed separately and then shaped to the desired dimensions and attached to the frame with the fasteners.
For example, the step of forming the first material can comprise electrospinning at least a portion of the plurality of fibers through at least one spinneret from a first solution comprising a first predetermined concentration of a silk fibroin at a predetermined extrusion rate on a first predetermined mandrel. In such exemplary aspects, the step of attaching then comprises i) shaping the first material to a predetermined dimension and ii) attaching the first material to the at least a portion of the inner surface of the annular frame.
Also disclosed are aspects where the step of forming the second material comprises electrospinning at least a portion of the plurality of fibers through at least one spinneret from a second solution comprising a second predetermined concentration of a silk fibroin at a predetermined extrusion rate on a second predetermined mandrel. In such exemplary aspects, the step of attaching then comprises i) shaping the second material to a predetermined dimension and ii) attaching the second material to the at least a portion of the outer surface of the annular frame.
Still further, the third material is formed by the electrospinning of the plurality of fibers on a third predetermined mandrel from a third solution comprising a third predetermined concentration of a silk fibroin at a predetermined extrusion rate. Then the third material can be laser cut to a predetermined shape.
In certain aspects, any of the predetermined concentrations of the silk fibroin in the first, second, or the third solution can be greater than 0 to less about 50% by weight, including exemplary values of about 0.1 wt %, about 0.2 wt %, about 0.3 wt %, about 0.5 wt %, about 0.6 wt %, about 0.7 wt %, about 0.8 wt %, about 0.9 wt %, about 1 wt %, about 2 wt %, about 3 wt %, about 4 wt %, about 5 wt %, about 6 wt %, about 7 wt %, about 8 wt %, about 9 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, about 40 wt %, and about 45 wt %. It is understood that the specific concentration can be chosen based on the desired application, and in some aspects, the concentration of silk fibroin in the first, the second, and/or the third solutions can be the same or different.
In still further aspects, any of the predetermined extrusion rate can be anywhere between 0.7 μl/hour to about 10,000 ml/hour, including exemplary values of about 0.8 μl/hour, about 1 μl/hour, about 2 μl/hour, about 5 μl/hour, about 10 μl/hour, about 20 μl/hour, about 50 μl/hour, about 100 μl/hour, about 250 μl/hour, about 500 μl/hour, about 1 ml/hour, about 10 ml/hour, about 50 ml/hour, about 100 ml/hour, about 250 ml/hour, about 500 ml/hour, about 750 ml/hour, about 1 ml/hour, about 10 ml/hour, about 50 ml/hour, about 100 ml/hour, about 250 ml/hour, about 500 ml/hour, about 750 ml/hour, about 1,000 ml/hour, about 1,250 ml/hour, about 1,500 ml/hour, about 2,000 ml/hour, about 3,000 ml/hour, about 4,000 ml/hour, about 5,000 ml/hour, about 6,000 ml/hour, about 7,000 ml/hour, about 8,000 ml/hour, about 9,000 ml/hour. It is also understood that the specific predetermined extrusion rate can be dependent on a volume of the syringe, a volume of the reservoir, pumping rate, etc. It is also understood that this parameter can be chosen on the specific applications and the component.
An exemplary electrospinning system 500 is shown in
In these exemplary and unlimiting aspects, the source of electrospinning material can include at least one syringe pump, at least one syringe mounted on the at least one syringe pump, and at least one syringe needle fluidly coupled to the at least one syringe, where the at least one syringe needle is a spinneret. However, it is understood that this description is only exemplary and unlimiting. In certain aspects, the source of electrospinning material can comprise an assembly comprising a plurality of spinnerets. In certain aspects, the plurality of spinnerets can comprise two or more needle spinnerets. In certain exemplary aspects, these two or more needle spinnerets can be arranged concentrically to allow, for example, formation of the disclosed above bicomponent fibers. It is understood that the bicomponent fibers can comprise a side-by-side configuration, a sheath-core configuration, a tri-lobal, an islands-in-the-sea configuration, a segmented pie configuration, or any combination thereof configurations. In such aspects, the spinnerets can be configured and arrange such the desired configuration of the final fiber is obtained. In aspects where the bicomponent fibers have a sheath-core configuration, the spinnerets can be arranged concentrically, such that the inner spinneret can be connected to electrospinning solution comprising the silk fibroin, while the outer spinneret can be connected to electrospinning solution comprising any of disclosed herein polymers. It is understood that the resulting bicomponent fiber will comprise a core comprising electrospun silk fibers and a sheath comprising any of the other polymers disclosed herein. In such exemplary aspects, the bicomponent fibers are disposed by electrospinning through at least two concentric spinnerets, wherein an outer spinneret is configured to extrude a sheath fiber from a fourth solution comprising a fourth predetermined concentration of silk fibroin, and wherein an inner spinneret is configured to extrude a core fiber from a fifth solution comprising a predetermined concentration of thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof at a predetermined extrusion rate. However, it is understood that the disclosed above procedure is only exemplary and a sheath of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber can comprise one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof. The predetermined extrusion can be any extrusion rate, as disclosed above.
In yet other aspects, the plurality of the needle spinneret can be arranged such that they can extrude fibers from different electrospinning solutions or the same electrospinning solution simultaneously. In such exemplary aspects, the plurality of spinneret needles can be arranged in any configuration allowing to achieve the desired result. For example, and without limitation, the plurality of needle spinnerets can be arranged in parallel or series. In still further aspects, each of the plurality of the needle spinneret can have the same diameter of the extrusion orifices, or it can be different depending on the desired result.
In yet further aspects, the assembly can comprise a plurality of needle-less spinnerets. In such exemplary and unlimiting aspects, various stationery and rotational needle-less spinnerets can be utilized. Any of the known in the art needle-less spinnerets can be used. Some exemplary aspects encompassing the needless spinneret assemblies are shown in
For example,
It is understood that needleless electrospinning can be dependent on the initiation of jets from an open liquid surface. When stationary spinnerets are employed, conical spikes are often created with the aid of an external force, such as magnetic force, high-pressure gas flow, and gravity. The known in the art stationary needle-less spinnerets that can be used in disclosed herein aspects are shown in
It is further understood that a type of the spinnerets used to form the disclosed herein materials can be chosen based on the desired application or scalability of the process. It is understood that in comparison with the needle electrospinning, the needle-less spinnerets can provide a higher output of the fibers (for example, the cylinder spinneret can provide about 8.6 g/hr, the disc spinneret can provide about 6.2 g/hr, and the ball spinneret can provide about 3.1 g/hr).
Still further, a specific choice of the spinneret can be determined by additional parameters. In some aspects, if the plurality of fibers having a finer average diameter is desired, the disc needle-less spinneret can be used (257±77 nm). Such a spinneret can provide fibers with a narrower diameter distribution compared to the ball (344±105 nm) and the cylinder (357±127 nm) spinnerets.
In still further aspects, the extrusion spinnerets can also be positioned within at least a portion of an inner space of the annular frame, where the inner space is defined by a circumference of the inner surface of the annular frame. In such exemplary aspects, at least one additional extrusion spinneret is also positioned outside of the annular frame. Such an exemplary aspect is shown in
In certain aspects, the electrospinning can occur simultaneously from the spinneret 1108 and 1106. While in other aspects, the fibers first electrospun from the spinneret 1106 and the from the spinneret 1108. However, it is understood that also the aspects, where the fibers are first electrospun from the spinneret 1108 and then spinneret 1106, are also disclosed. In some aspects, the electrospinning of the fibers can be done in a cycling manner. For example, and without limitations, a cycle of the electrospinning from the spinneret 1108 is followed by electrospinning from the spinneret 1106 and then followed again by the electrospinning from the spinneret 1108, etc. It is understood that the reverse order of using the spinnerets is also disclosed. It is also understood that the duration of each cycle can be determined by specific properties of the desired fibers, material thickness, material density and the like.
In some aspects, the spinnerets 1108 and 1106 can be connected to the same pump. While in other aspects, the spinnerets 1108 and 1106 can be separately assembled. It is understood that additional spinnerets can also be added to the inner space of the annular frame and/or outside of the annular frame. It is also understood that any of the disclosed herein spinnerets can be utilized.
Referring back to
It is understood, however, that this is only an exemplary solvent, and any other solvents can be used. The concentration of the silk fibroin in the solvent can be greater than 0 to less about 50% by weight, including exemplary values of about 0.1 wt %, about 0.2 wt %, about 0.3 wt %, about 0.5 wt %, about 0.6 wt %, about 0.7 wt %, about 0.8 wt %, about 0.9 wt %, about 1 wt %, about 2 wt %, about 3 wt %, about 4 wt %, about 5 wt %, about 6 wt %, about 7 wt %, about 8 wt %, about 9 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, about 40 wt %, and about 45 wt %. It is understood that the silk fibroin can be presented in any value between any foregoing values. In certain aspects, the silk fibroin can be fully dissolved in the solvent. While in other aspects, the silk fibroin can form a saturated solution. It is also understood that with an increase in polymer concentration, the average diameter of the fibers will also increase.
Still further and as disclosed herein, any one of the disclosed herein polymers can also be added to the solution of the silk fibroin in any desired concentration. For example, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof can be added to the solution comprising the silk fibroin. Any of the disclosed polymers can also be dissolved in any known in the art solvents. For example, the solvents used herein can comprise 2,2-Trifluoroacetic acid (TFA), dichloromethane (DCM), chloroform, methanol, formic acid, acetic acid, or chlorophenol, or any combinations thereof. It is also understood, and as described herein, in certain aspects, one or more separate electrospinning solutions can be utilized. In such aspects, any of the disclosed herein polymers can be present in these separate electrospinning solutions. The use of the separate electrospinning solutions having various combinations of the polymers and their concentration can allow a more precise control of the desired properties of the materials used to form the disclosed herein implantable devices. Additionally, one or more drugs and/or biologically active ingredients can be added to any of the described herein solutions.
In one exemplary aspect, the stent 604 can be any frame disclosed herein or known in the art. The stent 604 may be an expandable stainless-steel stent, or it can be a polymeric stent or it can be a nitinol stent. As disclosed, the material is not limited and can also include other materials such as cobalt-chrome alloys, for example.
The exemplary syringe pump 606 serves as the source of the electrospinning material 602 to be applied to frame 604. As disclosed in detail above, some aspects can include a plurality of syringe pumps. In general, electrospinning uses an electrical charge to draw very fine (typically on the micro- or nanometer scale) fibers from a liquid, such as a polymer solution or a polymer melt. In one electrospinning method, the polymer is discharged through a charged orifice toward a target, wherein the orifice and the target have opposing electrical charges. A voltage source is provided that creates a first charge at the charged orifice and an opposing charge at the target. The polymer is electrostatically charged by contact with the charged orifice. The electrostatically charged polymer is then collected at the target. Electrospinning of other than silk fibroin materials such as PET and PTFE are described in U.S. Patent Application Publication No. 2017/0325976 A1 and U.S. Patent Application Publication No. 2010/0193999 A1, which contents of both are incorporated herein by reference in their full entirety. Also, various aspects of the syringe pump 606, syringe needle, collector 608, controller 610, or mandrel 648 are disclosed in U.S. Patent Application Publication No. 2017/0325976 A1, which content is incorporated herein by reference in its full entirety.
The electrospinning material 602 is electrostatically drawn from the spinneret tip (not shown) by placing or applying a high voltage or potential difference between the spinneret tip and the collector 608 using a high-voltage power supply 630 connected by wires 632 to the spinneret and the collector. In one aspect, the high-voltage power supply 630 is an about 5 kV to 50 kV, including exemplary values of about 10 kV, about 15 kV, about 20 kV, about 25 kV, about 30 kV, about 35 kV, about 40 kV, and about 45 kV, direct-current power supply. In a particular aspect, the high-voltage power supply 630 is configured to apply any voltage within the described value to achieve the desired results.
It is understood that in certain aspects, the diameter of the fibers, their porosity, and mechanical strength can also be controlled by an amount of voltage applied to the system and by a specific polarity applied to the collector and the spinneret. It is understood that the higher the applied voltage, the average diameter of the obtained fiber will be smaller. Also, in some exemplary aspects, when the collector has a negative polarity, and the spinneret has a positive polarity, the finer fibers having a substantially uniform diameter (smaller standard deviation) can be obtained.
Referring back to
In certain aspects, the exemplary electrospinning systems, as shown in
Also, it is understood that the properties of the electrospun materials can be varied by varying various electrospinning parameters. For example, in certain aspects during the electrospinning of the at least a portion of the plurality of fibers to form the first material and/or the second material, the at least a portion of the inner surface or the outer surface, depending on the application, of the annular frame is positioned at a first predetermined distance or at a second predetermined distance, respectively from the at least one extrusion spinneret. Similarly, in other aspects, during the electrospinning of the at least a portion of the plurality of fibers to form the third material, the at least a portion of a third predetermined mandrel is positioned at a third predetermined distance from the at least one extrusion spinneret. The first, second, and/or predetermined distance can be the same or different, depending on the desired properties and can range from about 0.1 cm to about 200 cm, including exemplary values of 0.5 cm, about 1 cm, about 5 cm, about 10 cm, about 20 cm, about 50 cm, about 100 cm, about 125 cm, about 150 cm, and about 175 cm. It is understood that at shorter distances, larger fibers can be obtained. In certain aspects, and as disclosed herein, at least a portion of the annular frame can be positioned on a rotational drum configured to rotate at a predetermined speed. In such aspects, the predetermined speed can be from greater than 0 rpm to about 1,200 rpm, including exemplary values of about 5 rpm, about 10 rpm, about 20 rpm, about 50 rpm, about 100 rpm, about 200 rpm, about 300 rpm, about 400 rpm, about 500 rpm, about 600 rpm, about 700 rpm, about 800 rpm, about 900 rpm, about 1,000 rpm, and about 1,110 rpm. In still further aspects, the mandrel used to form the leaflet system can be stationary or rotational. If the mandrel is rotational, the predetermined speed of the mandrel can also be from greater than 0 rpm to about 1,200 rpm, including exemplary values of about 5 rpm, about 10 rpm, about 20 rpm, about 50 rpm, about 100 rpm, about 200 rpm, about 300 rpm, about 400 rpm, about 500 rpm, about 600 rpm, about 700 rpm, about 800 rpm, about 900 rpm, about 1,000 rpm, and about 1,110 rpm. It is further understood that the mechanical and scaffold properties of the formed materials can also be controlled by varying the rotating speed of the drum. For example, when the drum/mandrel is rotated slowly, the plurality of fibers can have a random orientation. While in other aspects, when the drum/mandrel is rotated faster, a more aligned orientation of the plurality of fibers can be obtained.
In still further aspects, it is understood that a plurality of various parameters can be used at once to control the desired mechanical and scaffold properties of the materials disclosed herein. For example, in some aspects, a first plurality of fibers can be formed at higher drum rotations combined with the higher voltages and farther distances, then a second plurality of fibers can be formed by slowing the drum rotations and/or decreasing the voltage and/or shortening the distance between the drum collector and the extrusion spinneret. It is understood that such manipulations of the process conditions can be used to obtain the desired average diameter of the fibers and the porosity of the formed materials.
It is also understood that the materials formed by the disclosed methods can be scaffold materials. The growth of the cells on the disclosed herein materials can also be controlled by controlling the average diameter of the fibers and the porosity of the material. Similarly, the skilled practitioner can tune the biodegradation and bioresorbability rate of the formed materials by precisely control and optimization of the average diameter of the fibers and the porosity.
In still further aspects, to increase the mechanical strength of the fibers, semi-liquid electrospinning processes can be utilized. In such exemplary aspects, a first plurality of layers can be electrospun when the collector is positioned at a distance close enough that a solvent present in the electrospinning solution does not evaporate before the electrospun fibers are formed on the collector. In such an exemplary aspect, the formed fibers are “semi-liquid.” Still further, after forming the first plurality of layers, the collector can be moved to a distance far enough to allow a solvent present in the electrospinning solution to evaporate before the electrospun fibers are formed on the collector and to form “dry fibers.” Such a sequence of forming different layers can be repeated as needed. Yet, in other aspects, a similar effect can be obtained by varying the extrusion rate. For example, and without limitation, the first plurality of layers can be deposited with a high extrusion rate, followed by forming the second plurality of layers deposited with a low extrusion rate, etc. Without wishing to be bound by any theory, it is hypothesized that during “semi-liquid”-“dry” electrospinning, a residual solvent penetrates various layers and improves the interconnectivity of the layers and, therefore, the overall strength of the material.
In still further aspects, to improve the mechanical strengths of the first, the second, and/or the third material, these materials can be chemically or physically treated. In some aspects, and as disclosed above, plasma treatment of the material can be applied. In such exemplary aspects, the plasma treatment can activate free radicals on the substrate, which then crosslinks and forms bonds with the depositing layer or amongst a polymeric chain of depositing nanofibers layers to increase the strength and change hydrophilicity/hydrophobicity of the material as disclosed above.
Yet, in further aspects, heat treatment can be used. While in yet other aspects, a freezing and thawing process can be utilized. In still further aspects, controllable welding can be used to improve the mechanical properties of the materials.
Still further and disclosed herein, prior to the step attaching the at least a portion of the first and/or the second material to the at least a portion of the annular frame, an adhesive material is applied to the at least a portion of the annular frame. While in other aspects, prior to forming the inner skirt and/or the outer skirt, at least a portion of the annular frame can be plasma treated.
As disclosed herein, the undulations of the plurality of the fibers can also be formed.
In still further aspects and as disclosed herein, the first, second, and/or third materials can be formed on separate and predetermined mandrels and then shaped to the desired dimensions.
In some of the aspects, any or all of the first, second, and/or third materials can further comprise at least one perforated material. In such aspects, the electrospun plurality of fibers can be disposed of the at least one perforated material.
It is understood that the at least one perforated material can be disposed on any surface of the electrospun plurality of fibers. In some aspects, for example, when the inner skirt is formed, the at least one perforated material can be disposed on the surface facing the annular frame. While in other aspects, it can be disposed on the surface facing the inner portion of the frame. Similarly, in the case of forming the outer skirt the perforated material can be disposed on the surface facing the annular frame or the surface facing the natural anatomy of the subject.
In yet other aspects, the third material can also comprise at least one perforated material that can be disposed on any or both of the surfaces of the third material.
It is understood that any combinations of the various configurations can be formed. For example, the first material can comprise at least one perforated material, while the second and the third materials are not. Yet, in other examples, the only second material can comprise at least one perforated material. While in still other examples, both the first and the second materials can comprise at least one perforated material. In a still further example, all three materials can comprise the at least one perforated material, and so on. In still further aspects, two or more perforated materials can be utilized. In some aspects, the plurality of fibers can be sandwiched between the perforated materials. In such aspects, the two perforated materials and the plurality of fibers can be coupled to each other. In still further aspects, two or more layers of the perforated material can be used on each or any surface of the disclosed herein materials. Any of the disclosed herein perforated materials can be utilized.
In some aspects, the plurality of the fibers of the first, second, and/or third materials can be directly electrospun on the at least one perforated material Yet, in other aspects, the plurality of the fibers of the first, second, and/or third materials can be attached to the at least one perforated material by any known in the art means. In some aspects, the attachment can be done with a fastener, for example, an adhesive or a suture. In yet other aspects, the plurality of fibers can be heat pressed to the perforated materials. In some aspects, the attachment can be done at any portion of the perforated material. For example, in some aspects, the attachment can be done throughout ail surfaces of the perforated material. While in other aspects, the attachment can be done only on one or more edges of the perforated material or anywhere on the surface of the perforated material in any desired pattern. It is understood that the placing of attachment and the amount of the surface that is physically attached to the plurality of fibers can vary depending on the desired applications.
In still further aspects and as disclosed above, the first, the second, and/or third materials can also comprise at least one auxiliary layer. Any of the disclosed above auxiliary layers can be utilized. Similarly, the auxiliary layer can be disposed at any surface of any of the disclosed herein materials. In some aspects, the auxiliary layer can be coated, can be sprayed, solution deposited, or otherwise applied by any known in the art methods. In some aspects, both the perforated material and auxiliary layer are present. In such aspects, the attachment between all the layers can be done throughout the whole material, one or more edges, or in any pattern as desired.
An alternative aspect of forming the disclosed implantable devices and materials is shown in
Rotary jet spinning systems and processes can involve imparting rotational motion to a reservoir holding any of the disclosed above polymer solutions, the rotational motion causing the polymer to be ejected from one or more orifices in the reservoir. Such processes can further involve collecting the formed fibers on a holder having a desired shape to form micron-, submicron- or nanometer-dimensioned polymeric fibers as a covering for component(s) of a medical implant device component.
The rotation of the mandrel 75 and holder 70 can be driven by a motor 11. Furthermore, the mandrel 75 and holder 70 may be mounted on a linear motor 12 configured to effect vertical translation of the mandrel 75 and holder 70. The motor 12 can be considered a fiber plane translation motor and may comprise, for example, a high uniaxial precision linear drive that is configured to translate the collector assembly 79 along an axis 13 parallel to the rotation axis 83 of the rotating reservoir 80, which corresponds to vertical translation with respect to the illustrated orientation of
The mandrel 75 and holder 70 can represent components of the collection assembly 79, at least part of which can be inserted into the path/plane 81 of the polymeric fibers 85. Axis 14, about which the mandrel/holder 70 is rotated, may be referred to as the collection rotation axis or mandrel/holder rotation axis. When the holder 70 is in the path/plane 81 of the polymeric fibers 85 ejected from the rotating reservoir 80, the polymeric fibers 85 can become wrapped around the holder 70 via rotation of the holder 70 about the collection rotation axis 14 as the holder 70 is translated along the axis 13.
In some aspects, methods of depositing fibrous material on a medical implant device component involve feeding any of the disclosed herein polymers into the rotating reservoir 80 and generating rotational motion at a speed, and for a time, sufficient to form a micron-, submicron-, or nanometer-dimensioned polymeric fiber, and collecting the formed fibers on a medical implant device to form the micron-, submicron-, or nanometer-dimensioned polymeric fiber covering in the desired shape/configuration. In some aspects, fibrous strands are produced by subjecting the polymer solution to a sufficient amount of pressure/stress for a time sufficient to form a fibrous covering on one or more components of a medical implant device in the desired shape and/or configuration. For example, sufficient pressure/stress to produce fibrous strands from the polymer solution can be about 3,000 Pascals or more.
In some aspects, the system 1000 is at least partially automated by control circuitry 5 configured to control one or more of the rotation rate of the reservoir 80, the rotation rate of the holder 70, and the linear and/or multi-dimensional translation of the holder 70 along the axis 13 parallel to the rotation axis 83 of the rotating reservoir and/or one or more other axes, through the generation and/or transmission of electrical signals to one or more components of the system 1000.
Control over the rate of translation of the holder 70 along the axis 13 and/or the orientation of the collection axis 14 relative to the reservoir rotation axis 83 can provide at least partial control over the orientation of fibers deposited on the collection holder 70. For example, fibers may be collected on the holder 70 substantially parallel to the reservoir rotation axis 83 and with slow translation along the collection rotation axis 14. In some implementations, the rotation of the collection device (e.g., holder 70) may be opposite the rotation of the reservoir 80 (e.g., counter-clockwise and clockwise, respectively), or the rotation of the collection device 70 may be the same as the rotation of the reservoir 80 (e.g., both counter-clockwise). In some implementations, by slowly moving the collection device (e.g., holder 70) along axis 13 through a path of the polymeric fibers 85 while rotating the collection device/assembly 70, completely aligned coverage of the holder and/or medical device component held thereby.
As shown in
In some aspects, the system 1000 includes a platform 10 for supporting the deposit of fibrous material, wherein the deposition assembly (80, 86) and the collection assembly (70, 71, 73, 76, 11) are disposed vertically above the platform 10 and/or spaced from the platform 10 along the vertical axis 13. Sufficient rotational speeds and times for operating the rotating structure 80 to form a fiber may be dependent on the concentration of the material/solution and the desired features of the formed fiber. Exemplary speeds of rotation of the rotating structure may range from about 100 rpm to about 500,000 rpm, although rotational speeds are not limited to this exemplary range. Furthermore, the rotating structure 80 may be rotated to impact the liquid material for a time sufficient to form a desired fiber, such as, for example, an amount of time between about 1-100 minutes, or other intermediate times or ranges are also intended to be part of this disclosure. The force or energy imparted by the rotating structure 80 advantageously overcomes the surface tension of the solution and decouples a portion of the liquid material at a meniscus thereof, and flings the portion away from the contact with the rotating structure and from a platform (not shown) on which the liquid is maintained, thereby forming fiber(s). The fiber(s) can be collected on the collection device 70. In some aspects, the direction in which the liquid material is flung may be substantially the same as the tangential direction of motion of the rotating structure of the reservoir 80 that contacts the liquid material. In some aspects, the rotating structure may impart a force to the liquid material in a substantially parallel direction to the top surface of the liquid material.
Any suitable size or geometrically-shaped reservoir 80 or collector 70 may be used for fabricating/collecting polymeric fibers. For example, reservoir 80 may be tubular, conical, semilunar, bicuspid, round, rectangular, or oval. The holder 70 may be round, oval, rectangular, or a half-heart shape. The holder 70 may also be shaped in the form of any living organ, such as a heart, kidney, liver lobe(s), bladder, uterus, intestine, skeletal muscle, or lung shape, or portion thereof. The holder 70 may further be shaped as any hollow cavity, organ or tissue, such as a circular muscle structure, e.g., a valve, sphincter, or iris.
The collection device 70 may be a holder configured in the desired shape and positioned in the path of the polymer ejected from the one or more orifices or in the path of the fibers flung from the rotating structure 80. In some aspects, the collection device 70 may be disposed at a distance of about 2 inches (about 5 cm) to about 12 inches (about 30 cm) from the reservoir 80 from which the polymer is ejected. Certain exemplary distances may include, but are not limited to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 inches (5, 7.6, 10.2, 12.7, 15.2, 17.8, 20.3, 22.9, 25.4, 27.9, 30 cm), and all intermediate numbers. This distance may be selected and/or configured to avoid formation of fibrous beads (which may occur if the collection device 70 is too close to the reservoir 80) and to achieve sufficient fibrous mass (which may not occur if the collection device is too far from the reservoir). In some implementations, the formation of fibrous beads is implemented intentionally to provide desired fiber characteristics. Still, other exemplary aspects of forming various implantable devices utilizing rotary jet spinning systems can be found in U.S. Patent Application No. 62/882,352, a content of which is incorporated herein in its whole entirety.
EXAMPLE 1: An implantable prosthetic valve comprising: an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; a leaflet structure positioned within the frame; an inner skirt positioned along the inner surface of the frame; at least one outer skirt positioned around the outer surface of the frame; wherein at least a portion of one of the leaflet structure, the inner skirt, or the at least one outer skirt comprises a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; and wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration.
EXAMPLE 2: The implantable prosthetic valve of any examples herein, particularly example 1, wherein at least a portion of the inner skirt comprises the material comprising the plurality of fibers, and wherein the material present in the at least a portion of the inner skirt is a first material, wherein the first material has a first surface facing the annular frame and an opposite second surface.
EXAMPLE 3: The implantable prosthetic valve of any examples herein, particularly example 1 or 2, wherein at least a portion of the outer skirt comprises the material comprising the plurality of fibers, and wherein the material present in the at least a portion of the outer skirt is a second material, wherein the second material has a first surface facing the annular frame and an opposite second surface.
EXAMPLE 4: The implantable prosthetic valve of any examples herein, particularly examples 1-3, wherein at least a portion of the leaflet structure comprises the material comprising the plurality of fibers, and wherein the material present in the at least a portion of the leaflet structure is a third material, wherein the third material has a first surface facing the annular frame and an opposite second surface.
EXAMPLE 5: The implantable prosthetic valve of any examples herein, particularly examples 2-4, wherein the first, second, and third materials are the same or different.
EXAMPLE 6: The implantable prosthetic valve of any examples herein, particularly examples 1-5, wherein each fiber of the plurality of fibers has a first extending direction and a plurality of undulations.
EXAMPLE 7: The implantable prosthetic valve of any examples herein, particularly example 6, wherein the first extending direction comprises a circumferential direction, a radial direction, or a combination thereof.
EXAMPLE 8: The implantable prosthetic valve of any examples herein, particularly example 6 or 7, wherein the plurality of undulations are present in the collapsed configuration.
EXAMPLE 9: The implantable prosthetic valve of any examples herein, particularly examples 6-8, wherein the plurality of undulations are configured to straighten when the implantable prosthetic valve is in the expanded configuration.
EXAMPLE 10: The implantable prosthetic valve of any examples herein, particularly examples 1-9, wherein the valve further comprises an adhesive material disposed between at least a portion of the annular frame and at least a portion of the outer skirt and/or between at least a portion of the annular frame and at least a portion of the inner skirt.
EXAMPLE 11: The implantable prosthetic valve of any examples herein, particularly examples 3-10, wherein at least a portion of the inner skirt is attached to the annular frame by direct electrospinning of the plurality of fibers on at least a portion of the inner surface of the annular frame.
EXAMPLE 12: The implantable prosthetic valve of any examples herein, particularly examples 4-11, wherein at least a portion of the outer skirt is attached to at least a portion of the annular frame by direct electrospinning of the plurality of fibers on at least a portion of the outer surface of the annular frame.
EXAMPLE 13: The implantable prosthetic valve of any examples herein, particularly examples 1-12, wherein at least a portion of the plurality of fibers has a random orientation.
EXAMPLE 14: The implantable prosthetic valve of any examples herein, particularly examples 1-13, wherein at least a portion of the plurality of fibers have a predetermined aligned orientation.
EXAMPLE 15: The implantable prosthetic valve of any examples herein, particularly examples 1-14, wherein the plurality of fibers further comprise a resorbable material, a non-resorbable material, or any combination thereof.
EXAMPLE 16: The implantable prosthetic valve of any examples herein, particularly examples 1-15, wherein at least one fiber the plurality of fibers further comprise thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), Polyvinylidene fluoride (PVDF), Polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 17: The implantable prosthetic valve of any examples herein, particularly examples 1-16, wherein the plurality of fibers comprises a bicomponent fiber.
EXAMPLE 18: The implantable prosthetic valve of any examples herein, particularly example 17, wherein the bicomponent fiber comprises a side-by-side configuration, a sheath-core configuration, an islands-in-the-sea configuration, a tri-lobal, a segmented pie configuration, or any combination thereof.
EXAMPLE 19: The implantable prosthetic valve of any examples herein, particularly example 18, wherein the bicomponent fiber comprises the sheath-core configuration.
EXAMPLE 20: implantable prosthetic valve of any examples herein, particularly example 19, wherein a sheath and/or a core of the bicomponent fiber comprises a resorbable material, a non-resorbable material, or any combination thereof.
EXAMPLE 21: The implantable prosthetic valve of any examples herein, particularly example 19 or 20, wherein a sheath of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), Polyvinylidene fluoride (PVDF), Polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane; polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), Polyvinylidene fluoride (PVDF), Polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 22: The implantable prosthetic valve of any examples herein, particularly examples 19-21, wherein a sheath of the bicomponent fiber comprises silk and wherein a core of the bicomponent fiber comprises one or more of thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 23: The implantable prosthetic valve of any examples herein, particularly examples 1-22, wherein the plurality of fibers have an average diameter from about 3 nm to about 15,000 nm.
EXAMPLE 24: The implantable prosthetic valve of any examples herein, particularly examples 2-23, wherein at least a portion of the first material, and/or the second material, and/or third material exhibits porosity.
EXAMPLE 25: The implantable prosthetic valve of any examples herein, particularly example 24, wherein the at least a portion of the first material and/or the second material, and/or third material have an average pore size from about 100 nm to about 100 μm.
EXAMPLE 26: The implantable prosthetic valve of any examples herein, particularly examples 2-25, wherein the first material and/or the second material, and/or third material comprise a plurality of layers, wherein each of the plurality of layers comprises electrospun silk, and wherein each of the plurality of layers is disposed on each other.
EXAMPLE 27: The implantable prosthetic valve of any examples herein, particularly example 26, wherein at least a first portion of the plurality of layers has a surface area that is substantially smaller than a surface area of a second portion of the plurality of layers surface area.
EXAMPLE 28: The implantable prosthetic valve of any examples herein, particularly examples 2-27, wherein the first material and/or the second material, and/or third material exhibit tensile strength from greater than 0 MPa to about 20 MPa.
EXAMPLE 29: The implantable prosthetic valve of any examples herein, particularly examples 2-28, wherein the first material and/or the second material, and/or third material exhibit elongation at break from greater than 0% to about 600%.
EXAMPLE 30: The implantable prosthetic valve of any examples herein, particularly examples 2-29 wherein the first material and/or the second material, and/or third material exhibit a water contact angle from about 0° to about 180°.
EXAMPLE 31: The implantable prosthetic valve of any examples herein, particularly examples 1-30, wherein at least a portion of the annular frame is plasma treated.
EXAMPLE 32: The implantable prosthetic valve of any examples herein, particularly examples 2-31, wherein at least a portion of the inner skirt comprising the first material is plasma treated.
EXAMPLE 33: The implantable prosthetic valve of any examples herein, particularly examples 3-32, wherein at least a portion of the outer skirt comprising the second material is plasma treated.
EXAMPLE 34: The implantable prosthetic valve of any examples herein, particularly examples 4-33, wherein at least a portion of the leaflet structure comprising the third material is plasma treated.
EXAMPLE 35: The implantable prosthetic valve of any examples herein, particularly examples 2-34, wherein the first material and/or the second material, and/or third material are at least partially biodegradable.
EXAMPLE 36: The implantable prosthetic valve of any examples herein, particularly examples 2-35, wherein the first material and/or the second material, and/or third material are at least partially bioresorbable.
EXAMPLE 37: The implantable prosthetic valve of any examples herein, particularly examples 16-36, the first material and/or the second material, and/or third material are at least partially degradable.
EXAMPLE 38: The implantable prosthetic valve of any examples herein, particularly examples 2-37, wherein the first material and/or the second material, and/or third material are a scaffold material.
EXAMPLE 39: The implantable prosthetic valve of any examples herein, particularly examples 2-10 or 13-38, wherein at least a portion of the inner skirt further comprises a first perforated material having a first surface facing the annular frame and an opposite second surface and wherein the first material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the first perforated material.
EXAMPLE 40: The implantable prosthetic valve of any examples herein, particularly examples 3-10 or 13-39, wherein at least a portion of the outer skirt further comprises a second perforated material having a first surface facing the annular frame and an opposite second surface and wherein the second material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the second perforated material.
EXAMPLE 41: The implantable prosthetic valve of any examples herein, particularly examples 4-10 or 13-40, wherein at least a portion of the leaflet structure comprises a third perforated material having a first surface facing the annular frame and an opposite second surface and wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the third perforated material.
EXAMPLE 42: The implantable prosthetic valve of any examples herein, particularly example 39-41, wherein the first perforated material, the second perforated material and/or the third perforated material are the same or different.
EXAMPLE 43: The implantable prosthetic valve of any examples herein, particularly example 2-10 or 13-42, wherein at least a portion of the first surface of the first material comprises a first auxiliary layer.
EXAMPLE 44: The implantable prosthetic valve of any examples herein, particularly example 2-10 or 13-43, wherein at least a portion of the second surface of the first material comprises a first auxiliary layer.
EXAMPLE 45: The implantable prosthetic valve of any examples herein, particularly example 44, wherein the first auxiliary layer present on the second surface of the first material is the same or different as the first auxiliary layer present on the first surface of the first material.
EXAMPLE 46: The implantable prosthetic valve of any examples herein, particularly example 3-10 or 13-45, wherein at least a portion of the first surface of the second material comprises a second auxiliary layer.
EXAMPLE 47: The implantable prosthetic valve of any examples herein, particularly example 3-10 or 13-46, wherein at least a portion of the second surface of the second material comprises a second auxiliary layer.
EXAMPLE 48: The implantable prosthetic valve of any examples herein, particularly example 47, wherein the second auxiliary layer present on the second surface of the second material is the same or different as the second auxiliary layer present on the first surface of the second material.
EXAMPLE 49: The implantable prosthetic valve of any examples herein, particularly example 4-10 or 18-48, wherein at least a portion of the first surface of the third material comprises a third auxiliary layer.
EXAMPLE 50: The implantable prosthetic valve of any examples herein, particularly example 4-10 or 13-49 wherein at least a portion of the second surface of the third material comprises a third auxiliary layer.
EXAMPLE 51: The implantable prosthetic valve of any examples herein, particularly example 50, wherein the third auxiliary layer present on the second surface of the third material is the same or different as the third auxiliary layer present on the first surface of the third material.
EXAMPLE 52: The implantable prosthetic valve of any examples herein, particularly example 43-51, wherein each of the first, second or third auxiliary layers are the same or different.
EXAMPLE 53: The implantable prosthetic valve of any examples herein, particularly example 41-52, wherein the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers that are resorbable, non-resorbable or a combination thereof.
EXAMPLE 54: The implantable prosthetic valve of any examples herein, particularly example 41-53, wherein the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers selected from polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyamide, polyethylene, terephthalate (PET polyethersulfone, poly-lactic-co-glycolic acid (PLGA) or a combination thereof or natural/regenerated fibers selected from cotton, silk, linen, cellulose acetate, collagen, or a combination thereof.
EXAMPLE 55: The implantable prosthetic valve of any examples herein, particularly example 50-53, wherein the first, second, and/or third auxiliary layer configured to impart to at least a portion of the first, second, and/or third material hydrophobic or hydrophilic properties, elastomeric properties, mechanical resilience, mechanical strength, adhesive properties, tissue-in-growth inhibition, or any combination thereof.
EXAMPLE 56: The implantable prosthetic valve of any examples herein, particularly example 55, wherein the first, second, and/or third auxiliary layer comprises one or more of resorbable, non-resorbable, or a combination thereof materials.
EXAMPLE 57: The implantable prosthetic valve of any examples herein, particularly example 55 or 56, wherein the first, second, and/or third auxiliary layer comprises one or more thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, or polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA).
EXAMPLE 58: The implantable prosthetic valve of any examples herein, particularly example 39-57, wherein at least a portion of the inner skirt further comprises at least two layers of the first perforated material, wherein the first material comprising the plurality of fibers is disposed between the two layers of the first perforated material, and wherein at the two layers of the first perforated material are at least partially coupled to each other.
EXAMPLE 59: The implantable prosthetic valve of any examples herein, particularly example 40-58, wherein at least a portion of the outer skirt further comprises at least two layers of the second perforated material, wherein the second material comprising the plurality of fibers is disposed between the two layers of the second perforated material and wherein at the two layers of the second perforated material are at least partially coupled to each other.
EXAMPLE 60: The implantable prosthetic valve of any examples herein, particularly example 41-59, wherein at least a portion of the leaflet structure further comprises at least two layers of the third perforated material, wherein the third material comprising the plurality of fibers is disposed between the two layers of the third perforated material; and wherein at the two layers of the third perforated material are at least partially coupled to each other.
EXAMPLE 61: The implantable prosthetic valve of any examples herein, particularly example 43, wherein at least a portion of the second surface of the first material is disposed on the first surface of the first perforated material.
EXAMPLE 62: The implantable prosthetic valve of any examples herein, particularly example 44, wherein at least a portion of the first surface of the first material is disposed on the second surface of the first perforated material.
EXAMPLE 63: The implantable prosthetic valve of any examples herein, particularly example 46, wherein at least a portion of the second surface of the second material is disposed on the first surface of the second perforated material.
EXAMPLE 64: The implantable prosthetic valve of any examples herein, particularly example 47, wherein at least a portion of the first surface of the second material is disposed on the second surface of the second perforated material.
EXAMPLE 65: The implantable prosthetic valve of any examples herein, particularly example 49, wherein at least a portion of the second surface of the third material is disposed on the first surface of the third perforated material.
EXAMPLE 66: The implantable prosthetic valve of any examples herein, particularly example 50, wherein at least a portion of the first surface of the third material is disposed on the second surface of the third perforated material.
EXAMPLE 67: The implantable prosthetic valve of any examples herein, particularly example 61-66, wherein at least a portion of the first auxiliary layer and the first perforated material is coupled to each other.
EXAMPLE 68: The implantable prosthetic valve of any examples herein, particularly example 63-67, wherein at least a portion of the second auxiliary layer and the second perforated material is coupled to each other.
EXAMPLE 69: The implantable prosthetic valve of any examples herein, particularly example 65-68, wherein at least a portion of the third auxiliary layer and the third perforated material is coupled to each other.
EXAMPLE 70: An article comprising a material comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprise electrospun silk, wherein the article has a collapsed configuration and an expanded configuration, and wherein the article is a part of an implantable device.
EXAMPLE 71: The article of any examples herein, particularly example 70, wherein the article is a paravalvular leak sealing article.
EXAMPLE 72: The article of any examples herein, particularly example 71, wherein the paravalvular leak sealing article comprises an inner skirt comprising a first material comprising a plurality of fibers and wherein the inner skirt is configured to be positioned on at least a portion of an inner surface of an annular frame of the implantable prosthetic device; wherein the first material has a first surface facing the annular frame and an opposite second surface.
EXAMPLE 73: The article of any examples herein, particularly example 71 or 72, wherein the paravalvular leak sealing article comprises an outer skirt comprising a second material comprising a plurality of fibers and wherein the outer skirt is configured to be positioned on at least a portion of an outer surface of an annular frame of the implantable prosthetic device; wherein the second material has a first surface facing the annular frame and an opposite second surface.
EXAMPLE 74: The article of any examples herein, particularly example 71-73, wherein the article comprises a leaflet structure comprising a third material comprising a plurality of fibers and wherein the leaflet structure is configured to be positioned within at least a portion of an annular frame of the implantable prosthetic device; wherein the third material has a first surface facing the annular frame and an opposite second surface.
EXAMPLE 75: The article of any examples herein, particularly example 70-74, wherein the material comprises the first material, or the second material, or the third material, or a combination thereof.
EXAMPLE 76: The article of any examples herein, particularly example 72-75, wherein the first, the second and the third materials are the same or different.
EXAMPLE 77: The article of any examples herein, particularly example 70-76, wherein each fiber of the plurality of fibers has a first extending direction and a plurality of undulations.
EXAMPLE 78: The article of any examples herein, particularly example 77, wherein the first extending direction comprises a circumferential direction, a radial direction, or a combination thereof.
EXAMPLE 79: The article of any examples herein, particularly example 77 or 78, wherein the plurality of undulations are present in the collapsed configuration.
EXAMPLE 80: The article of any examples herein, particularly example 77-79, wherein the plurality of undulations are configured to straighten when the article is in the expanded configuration.
EXAMPLE 81: The article of any examples herein, particularly example 72-80, wherein at least a portion of the inner skirt is attached to at least a portion of the annular frame by direct electrospinning of the plurality of fibers.
EXAMPLE 82: The article of any examples herein, particularly example 72-81, wherein at least a portion of the outer skirt is attached to at least a portion of the annular frame by direct electrospinning of the plurality of fibers.
EXAMPLE 83: The article of any examples herein, particularly examples 70-82, wherein at least a portion of the plurality of fibers has a random orientation.
EXAMPLE 84: The article of any examples herein, particularly example 71-83, wherein at least a portion of the plurality of fibers has a predetermined aligned orientation.
EXAMPLE 85: The article of any examples herein, particularly example 71-84, wherein the plurality of fibers further comprise a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 86: The article of any examples herein, particularly example 71-85, wherein at least one fiber the plurality of fibers further comprise thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 87: The article of any examples herein, particularly example 70-86, wherein the plurality of fibers comprises a bicomponent fiber.
EXAMPLE 88: The article of any examples herein, particularly example 87, wherein the bicomponent fiber comprises a side-by-side configuration, a sheath-core configuration, a tri-lobal, an islands-in-the-sea configuration, a segmented pie configuration, or any combination thereof.
EXAMPLE 89: The article of any examples herein, particularly example 88, wherein the bicomponent fiber comprises the sheath-core configuration.
EXAMPLE 90: The article of any examples herein, particularly example 89, wherein a sheath and/or core of the bicomponent fiber comprises a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 91: The article of any examples herein, particularly example 89 or 90, wherein a sheath of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-gycolic acid) (PLGA) or any combination thereof.
EXAMPLE 92: The article of any examples herein, particularly example 89, wherein a sheath of the bicomponent fiber comprises silk and wherein a core of the bicomponent fiber comprises one or more of thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 93: The article of any examples herein, particularly example 70-92, wherein the plurality of fibers have an average diameter from about 3 nm to about 15,000 nm.
EXAMPLE 94: The article of any examples herein, particularly example 72-93, wherein at least a portion of the first material and/or the second material and/or the third material exhibit porosity.
EXAMPLE 95: The article of any examples herein, particularly example 94 wherein the at least a portion of the first material and/or the second material and/or the third material have an average pore size from about 100 nm to about 100 μm.
EXAMPLE 96: The article of any examples herein, particularly example 72-95, wherein at least a portion of the first material and/or the second material and/or the third material exhibit comprise a plurality of layers, wherein each of the plurality of layers comprises electrospun silk, and wherein each of the plurality of layers is disposed on each other.
EXAMPLE 97: The article of any examples herein, particularly example 96, wherein at least a first portion of the plurality of layers has a surface area that is substantially smaller than a surface area of a second portion of the plurality of layers surface area.
EXAMPLE 98: The article of any examples herein, particularly example 72-97, wherein at least a portion of the first material and/or the second material and/or the third material exhibits tensile strength from greater than 0 MPa to about 20 MPa.
EXAMPLE 99: The article of any examples herein, particularly example 72-98, wherein at least a portion of the first material and/or the second material and/or the third material exhibit elongation at break from greater than 0% to about 600%.
EXAMPLE 100: The article of any examples herein, particularly example 72-99, wherein at least a portion of the first material and/or the second material and/or the third material exhibit a water contact angle from about 0° to about 180°.
EXAMPLE 101: The article of any examples herein, particularly example 72-100, wherein at least a portion of the first material comprising the plurality of fibers is plasma treated.
EXAMPLE 102: The article of any examples herein, particularly example 73-101, wherein at least a portion of the second material is plasma treated.
EXAMPLE 103: The article of any examples herein, particularly example 74-102, wherein at least a portion of the third material is plasma treated.
EXAMPLE 104: The article of any examples herein, particularly example 72-103, wherein at least a portion of the first material and/or the second material and/or the third material is at least partially biodegradable.
EXAMPLE 105: The article of any examples herein, particularly example 72-104, wherein at least a portion of the first material and/or the second material and/or the third material are at least partially bioresorbable.
EXAMPLE 106: The article of any examples herein, particularly example 83-105, wherein at least a portion of the first material and/or the second material and/or the third material are at least partially degradable.
EXAMPLE 107: The article of any examples herein, particularly example 72-106, wherein at least a portion of the first material and/or the second material and/or the third material are configured to be a scaffold material.
EXAMPLE 108: The article of any examples herein, particularly example 72-80 or 83-107, wherein at least a portion of the inner skirt further comprises a first perforated material having a first surface facing the annular frame and an opposite second surface and wherein the first material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the first perforated material.
EXAMPLE 109: The article of any examples herein, particularly example 73-80 or 83-108, wherein at least a portion of the outer skirt further comprises a second perforated material having a first surface facing the annular frame and an opposite second surface and wherein the second material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the second perforated material.
EXAMPLE 110: The article of any examples herein, particularly example 74-80 or 83-109, wherein at least a portion of the leaflet structure comprises a third perforated material having a first surface facing the annular frame and an opposite second surface and wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed on the first surface and/or the second surface of the third perforated material.
EXAMPLE 111: The article of any examples herein, particularly example 108-110, wherein the first perforated material, the second perforated material and/or the third perforated material are the same or different.
EXAMPLE 112: The article of any examples herein, particularly example 72-80 or 83-111, wherein at least a portion of the first surface of the first material comprises a first auxiliary layer.
EXAMPLE 113: The article of any examples herein, particularly example 72-80 or 83-112, wherein at least a portion of the second surface of the first material comprises a first auxiliary layer.
EXAMPLE 114: The article of any examples herein, particularly example 113, wherein the first auxiliary layer present on the second surface of the first material is the same or different as the first auxiliary layer present on the first surface of the first material.
EXAMPLE 115: The article of any examples herein, particularly example 72-80 or 83-114, wherein at least a portion of the first surface of the second material comprises a second auxiliary layer.
EXAMPLE 116: The article of any examples herein, particularly example 72-80 or 83-115, wherein at least a portion of the second surface of the second material comprises a second auxiliary layer.
EXAMPLE 117: The article of any examples herein, particularly example 47, wherein the second auxiliary layer present on the second surface of the second material is the same or different as the second auxiliary layer present on the first surface of the second material.
EXAMPLE 118: The article of any examples herein, particularly example 73-80 or 83-117, wherein at least a portion of the first surface of the third material comprises a third auxiliary layer.
EXAMPLE 119: The article of any examples herein, particularly example 73-80 or 83-118, wherein at least a portion of the second surface of the third material comprises a third auxiliary layer.
EXAMPLE 120: The article of any examples herein, particularly example 119, wherein the third auxiliary layer present on the second surface of the third material is the same or different as the third auxiliary layer present on the first surface of the third material.
EXAMPLE 121: The article of any examples herein, particularly example 112-120, wherein each of the first, second or third auxiliary layers are the same or different.
EXAMPLE 122: The article of any examples herein, particularly examples 108-121, wherein the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 123: The article of any examples herein, particularly examples 108-122, wherein the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers selected from polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA) or a combination thereof or natural/regenerated fibers selected from cotton, silk, linen, cellulose acetate, collagen, or a combination thereof.
EXAMPLE 124: The article of any examples herein, particularly examples 112-123, wherein the first, second, and/or third auxiliary layer configured to impart to at least a portion of the first, second, and/or third material hydrophobic or hydrophilic properties, elastomeric properties, mechanical resilience, mechanical strength, adhesive properties, tissue-in-growth inhibition, or any combination thereof.
EXAMPLE 125: The article of any examples herein, particularly example 124, wherein the first, second, and/or third auxiliary layer comprises one or more of a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 126: The article of any examples herein, particularly example 124 or 125, wherein the first, second, and/or third auxiliary layer comprises one or more thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, or polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA).
EXAMPLE 127: The article of any examples herein, particularly examples 108-126, wherein at least a portion of the inner skirt further comprises at least two layers of the first perforated material, wherein the first material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the first perforated material, and wherein at the two layers of the first perforated material are at least partially coupled to each other.
EXAMPLE 128: The article of any examples herein, particularly examples 109-127, wherein at least a portion of the outer skirt further comprises at least two layers of the second perforated material, wherein the second material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the second perforated material and wherein at the two layers of the second perforated material are at least partially coupled to each other.
EXAMPLE 129: The article of any examples herein, particularly examples 110-128, wherein at least a portion of the leaflet structure further comprises at least two layers of the third perforated material, wherein the third material comprising the plurality of fibers comprising the electrospun silk is disposed between the two layers of the third perforated material; and wherein at the two layers of the third perforated material are at least partially coupled to each other.
EXAMPLE 130: The article of any examples herein, particularly example 112, wherein at least a portion of the second surface of the first material is disposed on the first surface of the first perforated material.
EXAMPLE 131: The article of any examples herein, particularly example 113, wherein at least a portion of the first surface of the first material is disposed on the second surface of the first perforated material.
EXAMPLE 132: The article of any examples herein, particularly example 115, wherein at least a portion of the second surface of the second material is disposed on the first surface of the second perforated material.
EXAMPLE 133: The article of any examples herein, particularly example 116, wherein at least a portion of the first surface of the second material is disposed on the second surface of the second perforated material.
EXAMPLE 134: The article of any examples herein, particularly example 118, wherein at least a portion of the second surface of the third material is disposed on the first surface of the third perforated material.
EXAMPLE 135: The article of any examples herein, particularly example 119, wherein at least a portion of the first surface of the third material is disposed on the second surface of the third perforated material.
EXAMPLE 136: The article of any examples herein, particularly examples 130-135, wherein at least a portion of the first auxiliary layer and the first perforated material is coupled to each other.
EXAMPLE 137: The article of any examples herein, particularly examples 132-136, wherein at least a portion of the second auxiliary layer and the second perforated material is coupled to each other.
EXAMPLE 138: The article of any examples herein, particularly examples 134-137, wherein at least a portion of the third auxiliary layer and the third perforated material is coupled to each other.
EXAMPLE 139: A method of forming an implantable prosthetic valve comprising: a) providing an annular frame having an inner surface and an outer surface wherein the frame has an inflow end and an outflow end and a central longitudinal axis extending from the inflow end to the outflow end; b) forming an inner skirt comprising a first material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk; c) forming an outer skirt comprising a second material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber the plurality of fibers comprises electrospun silk; d) attaching the inner skirt to at least a portion of the inner surface of the annular frame and attaching the outer skirt to at least a portion of the outer surface of the annular frame, and wherein the implantable prosthetic valve is radially collapsible to a collapsed configuration and radially expandable to an expanded configuration.
EXAMPLE 140: The method of any examples herein, particularly example 139, wherein the step of forming the inner skirt and the step of attaching the inner skirt occurs simultaneously.
EXAMPLE 141: The method of any examples herein, particularly example 139, wherein the step of forming the inner skirt occurs prior to the step of attaching.
EXAMPLE 142: The method of any examples herein, particularly examples 139-141, wherein the step of forming the outer skirt and the step of attaching the outer skirt occurs simultaneously.
EXAMPLE 143: The method of any examples herein, particularly examples 139-141, wherein the step of forming the outer skirt occurs prior to the step of attaching.
EXAMPLE 144: The method of any examples herein, particularly examples 139-142, wherein the step of attaching the inner skirt occurs before or after the step of attaching the outer skirt.
EXAMPLE 145: The method of any examples herein, particularly examples 139-144, further comprising positioning a leaflet structure comprising a third material having a first surface and an opposite second surface and comprising a plurality of fibers, wherein at least one fiber of the plurality of fibers comprises electrospun silk within at least a portion of the annular frame.
EXAMPLE 146: The method of any examples herein, particularly example 145, wherein the step of positioning the leaflet structure occurs before or after the step of forming the inner skirt and/or outer skirt.
EXAMPLE 147: The method of any examples herein, particularly examples 145-146 wherein the first material, the second, and the third material are the same or different.
EXAMPLE 148: The method of any examples herein, particularly examples 140 or 143-147, wherein the step of simultaneously forming and attaching the inner skirt to the at least a portion of the inner surface of the annular frame comprises forming the first material by directly electrospinning at least a portion of the plurality of fibers through at least one spinneret from a first solution comprising a first predetermined concentration of a silk fibroin at a predetermined extrusion rate at the at least a portion of the inner surface of the annular frame.
EXAMPLE 149 The method of any examples herein, particularly examples 141-147, wherein the step of forming the first material comprises electrospinning at least a portion of the plurality of fibers through at least one spinneret from a first solution comprising a first predetermined concentration of a silk fibroin at a predetermined extrusion rate on a first predetermined mandrel.
EXAMPLE 150: The method of any examples herein, particularly example 149, wherein the step of attaching comprises i) shaping the first material to a predetermined dimension and ii) attaching the first material to the at least a portion of the inner surface of the annular frame.
EXAMPLE 151: The method of any examples herein, particularly examples 142 or 144-150, wherein the step of simultaneously forming and attaching the outer skirt to the at least a portion of the outer surface of the annular frame comprises forming the second material by directly electrospinning at least a portion of the plurality of fibers through at least one spinneret from a second solution comprising a second predetermined concentration of a silk fibroin at a predetermined extrusion rate the at least a portion of the outer surface of the annular frame.
EXAMPLE 152: The method of any examples herein, particularly examples 143-150, wherein the step of forming the second material comprises electrospinning at least a portion of the plurality of fibers through at least one spinneret from a second solution comprising a second predetermined concentration of a silk fibroin at a predetermined extrusion rate on a second predetermined mandrel.
EXAMPLE 153: The method of any examples herein, particularly example 152, wherein the step of attaching comprises i) shaping the second material to a predetermined dimension and ii) attaching the second material to the at least a portion of the outer surface of the annular frame.
EXAMPLE 154: The method of any examples herein, particularly examples 145-153, wherein the third material is formed by the electrospinning of the plurality of fibers on a third predetermined mandrel from a third solution comprising a third predetermined concentration of a silk fibroin at a predetermined extrusion rate.
EXAMPLE 155: The method of any examples herein, particularly example 154, wherein the third material is laser cut to form the leaflet structure.
EXAMPLE 156: The method of any examples herein, particularly examples 139-154, wherein prior to forming the inner skirt and/or the outer skirt, at least a portion of the annular frame is plasma treated.
EXAMPLE 157: The method of any examples herein, particularly examples 139-156, wherein prior to the step attaching the inner skirt and/or the outer skirt to the at least a portion of the inner surface and/the outer surface of the annular frame, respectively, an adhesive material is applied to the at least a portion of the inner surface and/or the outer surface of the annular frame.
EXAMPLE 158: The method of any examples herein, particularly examples 148 or 151-157, wherein during the electrospinning of the at least a portion of the plurality of fibers to form the first material, the at least a portion of the inner surface of the annular frame is positioned at a first predetermined distance from the at least one extrusion spinneret.
EXAMPLE 159: The method of any examples herein, particularly examples 149-151 or 154-157, wherein during the electrospinning of the at least a portion of the plurality of fibers to form the second material, the at least a portion of the outer surface of the annular frame is positioned at a second predetermined distance from the at least one extrusion spinneret.
EXAMPLE 160: The method of any examples herein, particularly examples 148, 151, or 156-160, wherein the at least one extrusion spinneret is positioned outside of the annular frame.
EXAMPLE 161: The method of any examples herein, particularly examples 148, 151, or 156-160, wherein the at least one extrusion spinneret is positioned within at least a portion of an inner space of the annular frame, wherein the inner space is defined by a circumference of the inner surface of the annular frame.
EXAMPLE 162: The method of any examples herein, particularly example 161, wherein the electrospinning occurs simultaneously from the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and from the at least one additional spinneret that is positioned outside of the annular frame.
EXAMPLE 163: The method of any examples herein, particularly example 161, wherein the electrospinning occurs first from the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and then from the at least one additional spinneret that is positioned outside of the annular frame.
EXAMPLE 164: The method of any examples herein, particularly example 161, wherein the electrospinning occurs first from the at least one additional spinneret that is positioned outside of the annular frame and then from the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame.
EXAMPLE 165: The method of any examples herein, particularly example 163 or 164, wherein the electrospinning is performed by cycling.
EXAMPLE 166: The method of any examples herein, particularly examples 161-165, wherein the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and the at least one additional spinneret positioned outside of the annular frame has an extrusion rate that is the same or different.
EXAMPLE 167: The method of any examples herein, particularly examples 161-166, wherein each of the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular space and the at least one additional spinneret positioned outside are configured to electrospun a plurality of fibers from a solution having the same or different concentration of a silk fibroin.
EXAMPLE 168: The method of any examples herein, particularly examples 161-167, wherein the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame at a third distance from the annular frame and is configured to be moved within the inner space of the annular frame.
EXAMPLE 169: The method of any examples herein, particularly example 168, wherein the third predetermined distance from the annular frame is adjustable.
EXAMPLE 170: The method of any examples herein, particularly examples 161-167, wherein the at least one additional spinneret positioned outside of the annular frame is positioned at a fourth predetermined distance from the annular frame.
EXAMPLE 171: The method of any examples herein, particularly example 169, wherein the fourth predetermined distance from the annular frame is adjustable.
EXAMPLE 172: The method of any examples herein, particularly example 170 or 171, wherein the first, second, third and/or fourth predetermined distances are the same or different.
EXAMPLE 173: The method of any examples herein, particularly examples 162-172, wherein the plurality of fibers formed by the at least one extrusion spinneret positioned within the at least a portion of the inner space of the annular frame and the at least one additional spinneret positioned outside of the annular frame are consolidated.
EXAMPLE 174: The method of any examples herein, particularly examples 154-173, wherein during the electrospinning of the at least a portion of the plurality of fibers to form the third material, the at least a portion of the third predetermined mandrel is positioned at a third predetermined distance from the at least one extrusion spinneret.
EXAMPLE 175: The method of any examples herein, particularly examples 154-174, wherein during the electrospinning of the at least a portion of the plurality of fibers to form the first material and/or the second material and/or the third material, the at least a portion of the inner surface of the annular frame and/or the at least a portion of the outer surface of the annular frame and/or the at least a portion of the first, second and/or third predetermined mandrels are positioned at a distance from the at least one extrusion spinneret such that the distance is varied during the electrospinning to form one or more plurality of layers within at least a portion of the first material and/or the second material and/or the third material.
EXAMPLE 176: The method of any examples herein, particularly examples 148-175, wherein at least a portion of the annular frame is positioned on a rotational drum configured to rotate at a predetermined speed.
EXAMPLE 177: The method of any examples herein, particularly examples 152-176, wherein the first, second, and/or third predetermined mandrels are configurated to be rotational or stationary.
EXAMPLE 178: The method of any examples herein, particularly example 176 or 177, wherein a first predetermined voltage is applied between the rotational drum and the at least one spinneret.
EXAMPLE 179: The method of any examples herein, particularly examples 152-178, wherein a second predetermined voltage is applied between the first, second and/or third predetermined mandrels and the at least one spinneret.
EXAMPLE 180: The method of any examples herein, particularly examples 148-179, wherein the at least one spinneret comprises a needle.
EXAMPLE 181: The method of any examples herein, particularly examples 148-180, wherein the at least one spinneret is a part of an assembly comprising a plurality of spinnerets.
EXAMPLE 182: The method of any examples herein, particularly example 181, wherein the assembly comprises a plurality of needle-less spinnerets.
EXAMPLE 183: The method of any examples herein, particularly examples 145-182, wherein the plurality of fibers present in the first material and/or the second material and/or the third material comprise a first extending direction and a plurality of undulations.
EXAMPLE 184: The method of any examples herein, particularly example 183, wherein the first extending direction comprises a circumferential direction, a radial direction, or a combination thereof.
EXAMPLE 185: The method of any examples herein, particularly example 183 or 184, wherein the plurality of undulations are present in the collapsed configuration of the implantable prosthetic valve.
EXAMPLE 186: The method of any examples herein, particularly examples 183-185, wherein the plurality of undulations are configured to straighten when the implantable prosthetic valve is in the expanded configuration.
EXAMPLE 187: The method of any examples herein, particularly examples 145-186, wherein at least a portion of the plurality of fibers present in the first material and/or the second material and/or the third material has a random orientation.
EXAMPLE 188: The method of any examples herein, particularly examples 145-187, wherein at least a portion of the plurality of fibers present in the first material and/or the second material and/or the third material has a predetermined aligned orientation.
EXAMPLE 189: The method of any examples herein, particularly examples 145-188, wherein the plurality of fibers present in the first material and/or the second material and/or the third material further comprise a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 190: The method of any examples herein, particularly examples 145-189, wherein the plurality of fibers present in the first material and/or the second material and/or the third material further comprise thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), Polyvinylidene fluoride (PVDF), Polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 191: The method of any of one of any examples herein, particularly examples 145-190, wherein the plurality of fibers are disposed by electrospinning through the at least one spinneret from the first solution and/or the second solution and/or the third solution further comprising a predetermined concentration of a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 192: The method of any examples herein, particularly example 190, wherein the plurality of fibers are disposed by electrospinning through the at least one spinneret from the first solution and/or the second solution and/or the third solution further comprising a predetermined concentration of the thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof at a predetermined extrusion rate.
EXAMPLE 193: The method of any examples herein, particularly examples 140-192, wherein at least a portion of the plurality of fibers present in the first material and/or the second material, and/or the third material comprises a bicomponent fiber.
EXAMPLE 194: The method of any examples herein, particularly example 193, wherein the bicomponent fiber comprises a side-by-side configuration, a sheath-core configuration, a tri-lobal, an islands-in-the-sea configuration, a segmented pie configuration, or any combination thereof.
EXAMPLE 195: The method of any examples herein, particularly example 194, wherein the bicomponent fiber comprises the sheath-core configuration.
EXAMPLE 196: The method of any examples herein, particularly example 195, wherein a sheath and a core of the bicomponent fiber comprises a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 197: The method of any examples herein, particularly example 195, wherein a sheath of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU): implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof; and wherein a core of the bicomponent fiber comprises one or more of silk, thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluorethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polyolefins such as, polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 198: The method of any examples herein, particularly example 195 or 197, wherein a sheath of the bicomponent fiber comprises silk and wherein a core of the bicomponent fiber comprises one or more of thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof.
EXAMPLE 199: The method of any examples herein, particularly example 198, wherein the bicomponent fibers are disposed by electrospinning through at least two concentric spinnerets, wherein an outer spinneret is configured to extrude a sheath fiber from a fourth solution comprising a fourth predetermined concentration of silk fibroin, and wherein an inner spinneret is configured to extrude a core fiber from a fifth solution comprising a predetermined concentration of a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 200: The method of any examples herein, particularly example 198, wherein the bicomponent fibers are disposed by electrospinning through at least two concentric spinnerets, wherein an outer spinneret is configured to extrude a sheath fiber from a fourth solution comprising a fourth predetermined concentration of silk fibroin, and wherein an inner spinneret is configured to extrude a core fiber from a fifth solution comprising a predetermined concentration of thermoplastic polyurethane (TPU), polyurethane (PU), implantable elastane polymer, polyester (PET), ultra-high molecular weight polyethylene (UHMWPE), polytetrafluorethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), polyamides (Nylons), polypropylene, polyetheretherketone (PEEK), polyglycolic acid (PGA), poly(ester urethane)urea, polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or any combination thereof at a predetermined extrusion rate.
EXAMPLE 201: The method of any examples herein, particularly examples 145-200, wherein the plurality of fibers present in the first material and/or the second material and/or the third material have an average diameter from about 3 nm to about 15,000 nm.
EXAMPLE 202: The method of any examples herein, particularly examples 145-201, wherein at least a portion of the first material and/or the second material and/or the third material exhibit porosity.
EXAMPLE 203: The method of any examples herein, particularly example 202, wherein the at least a portion of the first material and/or the second material, and/or third material have an average pore size from about 100 nm to about 100 μm.
EXAMPLE 204: The method of any examples herein, particularly examples 145-203, wherein the first material and/or the second material, and/or third material comprise a plurality of layers, wherein each of the plurality of layers comprises electrospun silk, and wherein each of the plurality of layers is disposed on each other.
EXAMPLE 205: The method of any examples herein, particularly example 204, wherein the at least a first portion of the plurality of layers has a surface area that is substantially smaller than a surface area of a second portion of the plurality of layers surface area.
EXAMPLE 206: The method of any examples herein, particularly examples 145-205, wherein the first material and/or the second material and/or the third material exhibit tensile strength from greater than 0 MPa to about 20 MPa.
EXAMPLE 207: The method of any examples herein, particularly examples 145-206, wherein the first material and/or the second material and/or the third material exhibit elongation at break from greater than 0% to about 600%.
EXAMPLE 208: The method of any examples herein, particularly examples 145-207, wherein the first material and/or the second material and/or the third material exhibit a water contact angle from about 0° to about 180°.
EXAMPLE 209: The method of any examples herein, particularly examples 145-208, wherein at least a portion of the first material and/or the second material and/or the third material is biodegradable.
EXAMPLE 210: The method of any examples herein, particularly examples 145-209, wherein at least a portion of the first material and/or the second material and/or the third material is bioresorbable.
EXAMPLE 211: The method of any examples herein, particularly examples 145-210, wherein at least a portion of the first material and/or the second material and/or the third material is degradable.
EXAMPLE 212: The method of any examples herein, particularly examples 139-211, wherein at least a portion of the first material and/or the second material and/or the third material is configured to be a scaffold material.
EXAMPLE 213: The method of any examples herein, particularly examples 154-212, wherein at least a portion of the plurality of fibers at present in the first material and/or the second material and/or the third material is plasma treated after electrospinning.
EXAMPLE 214: The method of any examples herein, particularly examples 150-213, wherein at least a portion of the formed first material is disposed on a first perforated material having a first surface and an opposite second surface prior to the step of attaching, and wherein the first material is disposed on the first surface and/or the second surface of the first perforated material.
EXAMPLE 215: The method of any examples herein, particularly example 214, wherein the step of attaching comprises coupling the first surface of the first perforated material to at least a portion of the annular frame.
EXAMPLE 216: The method of any examples herein, particularly examples 152-215, wherein at least a portion of the formed second material is disposed on a second perforated material having a first surface and an opposite second surface prior to the step of attaching, and wherein the second material is disposed on the first surface and/or the second surface of the second perforated material.
EXAMPLE 217: The method of any examples herein, particularly example 216, wherein the step of attaching comprises coupling the first surface of the second perforated material to at least a portion of the annular frame.
EXAMPLE 218: The method of any examples herein, particularly examples 154-217, wherein at least a portion of the leaflet structure is disposed on a third perforated material having a first surface and an opposite second surface and wherein the third material is disposed on the first surface and/or the second surface of the third perforated material.
EXAMPLE 219: The method of any examples herein, particularly example 218, wherein the first perforated material, the second perforated material and/or the third perforated material are the same or different.
EXAMPLE 220: The method of any examples herein, particularly examples 150-219, comprising disposing a first auxiliary layer at at least a portion of the first surface of the first material.
EXAMPLE 221: The method of any examples herein, particularly examples 150-220, comprising disposing a first auxiliary at at least a portion of the second surface of the first material.
EXAMPLE 222: The method of any examples herein, particularly example 221, wherein the first auxiliary layer present on the second surface of the first material is the same or different as the first auxiliary layer present on the first surface of the first material.
EXAMPLE 223: The method of any examples herein, particularly examples 153-222, comprising a second auxiliary layer at at least a portion of the first surface of the second material.
EXAMPLE 224: The method of any examples herein, particularly examples 153-223, comprising disposing a second auxiliary layer at at least a portion of the second surface of the second material.
EXAMPLE 225: The method of any examples herein, particularly example 224, wherein the second auxiliary layer present on the second surface of the second material is the same or different as the second auxiliary layer present on the first surface of the second material.
EXAMPLE 226: The method of any examples herein, particularly examples 154-225 comprises disposing a third auxiliary layer at at least a portion of the first surface of the third material.
EXAMPLE 227: The method of any examples herein, particularly examples 154-225, comprises disposing a third auxiliary layer at at least a portion of the second surface of the third material.
EXAMPLE 228: The method of any examples herein, particularly example 227, wherein the third auxiliary layer present on the second surface of the third material is the same or different as the third auxiliary layer present on the first surface of the third material.
EXAMPLE 229: The method of any examples herein, particularly examples 227-228, wherein each of the first, second or third auxiliary layers are the same or different.
EXAMPLE 230: The method of any examples herein, particularly examples 219-229, wherein the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 231: The method of any examples herein, particularly examples 219-230, wherein the first, second, and/or third perforated material comprises a porous fabric or membrane, wherein the porous fabric or membrane comprises one or more biocompatible polymers selected from polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), thermoplastic polyurethane (TPU), polyurethane (PU); implantable elastane polymer, polyamide, polyethylene terephthalate (PET), polyethersulfone, poly-lactic-co-glycolic acid (PLGA) or a combination thereof or natural/regenerated fibers selected from cotton, silk, linen, cellulose acetate, collagen or a combination thereof.
EXAMPLE 232: The method of any examples herein, particularly examples 227-231, wherein the first, second, and/or third auxiliary layer configured to impart to at least a portion of the first, second, and/or third material hydrophobic or hydrophilic properties, elastomeric properties, mechanical resilience, adhesive properties, tissue-in-growth inhibition, or any combination thereof.
EXAMPLE 233: The method of any examples herein, particularly example 232, wherein the first, second, and/or third auxiliary layer comprises a resorbable material, a non-resorbable material, or a combination thereof.
EXAMPLE 234: The method of any examples herein, particularly example 232 or 233, wherein the first, second, and/or third auxiliary layer comprises one or more thermoplastic polyurethane (TPU), polyurethane (PU): implantable elastane polymer, or polyethylene, polypropylene, polymethylmethacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), polyamide, polyethylene terephthalate (PET, polyethersulfone, poly-lactic-co-glycolic acid (PLGA).
EXAMPLE 235: The method of any examples herein, particularly examples 150-234, comprising disposing the first material between two layers of the first perforated material, and wherein the two layers of the first perforated material are at least partially coupled to each other.
EXAMPLE 236: The method of any examples herein, particularly examples 151-235, comprising the second material disposed between two layers of the second perforated material and wherein at the two layers of the second perforated material are at least partially coupled to each other.
EXAMPLE 237: The method of any examples herein, particularly examples 154-236, comprising disposing the third material between two layers of the third perforated material; and wherein at the two layers of the third perforated material are at least partially coupled to each other.
EXAMPLE 238: The method of any examples herein, particularly example 220, wherein at least a portion of the second surface of the first material is disposed on the first surface of the first perforated material.
EXAMPLE 239: The method of any examples herein, particularly example 221, wherein at least a portion of the first surface of the first material is disposed on the second surface of the first perforated material.
EXAMPLE 240: The method of any examples herein, particularly example 223, wherein at least a portion of the second surface of the second material is disposed on the first surface of the second perforated material.
EXAMPLE 241: The method of any examples herein, particularly example 224, wherein at least a portion of the first surface of the second material is disposed on the second surface of the second perforated material.
EXAMPLE 242: The method of any examples herein, particularly example 226, wherein at least a portion of the second surface of the third material is disposed on the first surface of the third perforated material.
EXAMPLE 243: The method of any examples herein, particularly example 231, wherein at least a portion of the first surface of the third material is disposed on the second surface of the third perforated material.
EXAMPLE 244: The method of any examples herein, particularly examples 238-243, wherein at least a portion of the first auxiliary layer and at least a portion of the first perforated material are coupled to each other.
EXAMPLE 245: The method of any examples herein, particularly examples 240-244, wherein at least a portion of the second auxiliary layer and at least a portion of the second perforated material are coupled to each other.
EXAMPLE 246: The method of any examples herein, particularly examples 242-245, wherein at least a portion of the third auxiliary layer and at least a portion of the third perforated material are coupled to each other.
Although several aspects of the disclosure have been disclosed in the foregoing specification, it is understood by those skilled in the art that many modifications and other aspects of the disclosure will come to mind to which the disclosure pertains, having the benefit of the teaching presented in the foregoing description and associated drawings. It is thus understood that the disclosure is not limited to the specific aspects disclosed hereinabove and that many modifications and other aspects are intended to be included within the scope of the appended claims. Moreover, although specific terms are employed herein, as well as in the claims which follow, they are used only in a generic and descriptive sense and not for the purposes of limiting the described disclosure nor the claims which follow. We, therefore, claim as our disclosure all that comes within the scope and spirit of these claims
This application is a continuation of International Application No. PCT/US2021/016132, filed Feb. 2, 2021, which claims the benefit of U.S. Provisional Application No. 63/016,835, filed Apr. 28, 2020, the content of which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US2021/016132 | Feb 2021 | US |
| Child | 18050415 | US |
