Patent Application
20220313233
The present invention relates to a medical implant, in particular a patch, a delivery device for a medical implant, and a method of delivering a medical implant according to the preamble of the independent claims.
Defects in tissue, for example atrial septal defects (ASDs) or ventricular septal defects (VSDs), are fairly common conditions in humans that are typically treated minimally invasively or surgically. Such defects can cause a variety of symptoms such as shortness of breath and a higher burden on the heart and lungs.
As a consequence, a myriad of implantable devices has been proposed in the prior art, many of which can be deployed in a minimally invasive way.
For example, closure of an atrial septal defect (ASD) by deploying umbrella-like implants through a catheter have been disclosed by Lock et al. (DOI: 10.1161/01.CIR.79.5.1091).
However, known implants exhibit several disadvantages. Typically, they are attached to a tissue wall, or held in place, mechanically. On one hand, this can lead to small injuries of the tissue to be treated. On the other hand, mechanical attachment places constraints on the material choice and mechanical strength of the used components. Finally, mechanical anchoring can also be difficult to realize in a minimally invasive treatment.
Thus, the object of the present invention is to overcome the drawbacks of the prior art, in particular to provide a medical implant, a device for delivering an implant, and a method of delivering an implant that is easy and safe to use.
This and other objects are achieved by the medical implant, the delivery device and the methods according to the characterizing portion of the independent claims of the invention.
The medical implant according to the invention is adapted to repair or close a defect, in particular an opening in a ventricular, atrial, or septal wall. In particular, the medical implant may be a patch, for example a polymeric or pericardial patch. It comprises an adhesive composition. It further comprises two states, wherein in the first state, the medical implant can be deployed to an implant site while the adhesive composition is inactive. It can be brought into a second state, preferably at the implant site, by an activation mechanism. The adhesive composition, in the second state, is curable by a curing mechanism. In particular, it is conceivable that the activation mechanism is identical to the curing mechanism. Alternatively, two different mechanisms may be employed for activation and curing.
The medical implant may also be suitable to close a cavity, such as a left atrial appendage. In particular, the implant may be sized and shaped such that the implant may be attached an ostium of a cavity.
The curing mechanism may in particular be exposure to electromagnetic radiation, for example exposure to visible light, UV light, IR light, and/or X-rays. Curing may, in particular, include cross-linking of the adhesive.
A patch shall be understood as a substantially flat structure. Preferably, it is mechanically flexible such that it can adapt to an underlying surface shape or structure.
The implant is preferably adapted in size and shape to close an opening in a ventricular and atrial septal wall, for example a patent foramen ovale (PFO). Typically, a medical implant for such an application has a substantially round, preferably circular, shape, though any shape such as a triangle, square, or more complicated shape is possible. It is substantially flat, and has a typical diameter of 20-30 mm, preferably 20-25 mm. It may of course be larger or smaller, depending on a patient or the opening to be treated. For example, an opening in the heart of a child may be smaller, requiring a patch diameter as small as 10 mm. It may also be as large as 30 mm, for example if a patient is very tall. Typically, the thickness of the medical implant is 100-200 μm. Of course, the thickness may also be adapted and be as thin as 50 μm or as thick as 1.5 mm, preferably as thick as 1 mm, particularly preferably as thick as 500 μm.
Preferably, the medical implant comprises a material with self-healing and/or self-closing properties. Such properties enable easier implantation because the implant can be temporarily held with an instrument through a hole, for example with a needle and/or a suture, wherein the hole closes automatically after implantation.
Additionally or alternatively, the implant may comprise a hole in a center region that enables or assists holding with a delivery instrument.
In general, materials with high flexibility are preferred materials for the implant according to the invention. A high flexibility reduces the risk of tear, rupture and/or dislodgment during and after implantation. However, it will be understood that rigid materials, in principle, are also suitable for the implants disclosed herein.
Preferably, in the first state, the medical implant comprises at least one cavity that contains the adhesive composition. Preferably, the medical implant comprises a plurality of cavities. It may be adapted to, in the second state, release the adhesive composition.
A cavity shall be understood as a closed structure in the medical implant that can retain another substance such as a liquid, a viscous liquid, or even a solid. For example, the cavity may be a large hollow structure or a small pore. Cavities are particularly advantageous to store the adhesive composition in the first state because the adhesive is protected from the surrounding media, in particular humidity/moisture from the body, for example originating from as bodily fluids. Thus, it does not accidentally engage tissue before activation, and prevents problem while deploying the medical implant, such as clogging of a catheter due to adhesive leaks.
In general, the adhesive may also be electrically activatable. An example of an electrically activatable glue is voltaglue, for example as disclosed in ACS Appl. Bio Mater. 2019, 2, 6, 2633-2642, which is incorporated here by reference. However, any other electrically activatable glue is suitable. In general, such glues may contain an element or molecule that can form a radical when exposed to a voltage. The formed radicals may cause cross-linking.
Preferably, the implant is manufactured by an additive manufacturing/3D-printing method.
Preferably, the implant comprises optical fibers for distribution of light within the implant. For example, the optical fibers may comprise or consist of glass, a polymer, or particularly preferably a biodegradable polymer.
The cavities may have at least two boundary surfaces. At least one property of the boundary surfaces is different between one boundary surface and the other. Preferably, the property includes at least one of a permeability and solubility.
For example, the boundary surfaces may differ in the permeability for an adhesive such as to preferentially release the adhesive at a particular location or side of the cavity. Additionally or alternatively, the permeability for blood or another bodily fluid may differ.
Additionally or alternatively, the boundary surfaces may differ in their solubility in blood or another bodily fluid. Such a difference in solubility may cause preferential release of an adhesive at a particular location or side of the cavity.
In particular, at least one of the boundary surfaces may comprise, preferably consist of, at least one of PEG, PLA, PET, PUs.
The two different surfaces may also be configured such that one surface is adapted to provide adhesion to tissue, while the other surface is adapted to enhance tissue and/or cell growth.
The medical implant may comprise a radio-opaque element. A radio-opaque element may be any element that provides contrast in radio-imaging. Preferably, the radio-opaque element comprises, in particular consists of, barium sulphate, platinum, iridium, and/or tungsten. The radio-opaque element may, in particular, be a wire, a particle, or another marker.
Preferably, the medical implant comprises a support structure, wherein the radio-opaque element is arranged within or formed by the support structure. For example, the medical implant may comprise a backbone made of a polymer that comprises at least one, preferably a plurality of, barium sulphate particles. Alternatively, a similar backbone may be made of a metal that is radio-opaque.
Particularly preferably, a plurality of radio-opaque elements may be arranged in a particular pattern, spacing, geometry or alignment such that data on the relative positions of the radio-opaque elements, for example their spacing and/or alignment determined from imaging data, may provide information about proper adhesion and/or positioning of the medical implant. For example, three markers may be equally spaced around the circumference of the implant. Additionally or alternatively, the radio-opaque element may have a particular shape that provides information on adhesion and/or position of the implant. For example, the radio-opaque element may have a bent shape, which is kept straight by the adhesive force when the implant is attached to a straight surface. Thus, if a bent shape is determined via radio imaging, it would indicate that the medical device is detaching from the tissue. In particular, the radio-opaque element may be adapted such as to not exert a force that is sufficient to dislodge the implant.
Preferably, the radio-opaque element is arranged within or formed by the adhesive composition. For example, barium sulphate particles may be dispersed in the adhesive composition. Additionally or alternatively, the adhesive may comprise a coordination polymer comprising barium ions. Additionally or alternatively, the radio-opaque element may comprise or consist of barium sulphate, iodine, tantalum, iridium, and/or iohexol, which may also be dispersed in the adhesive.
Preferably, the radio-opaque element comprises at least one of barium sulphate and iodine. Iodine is particularly advantageous if the radio-opaque element is used to track the degradation of an adhesive, a patch material, or other parts of the implant. For example, if the medical implant is designed to degrade in the human body while allowing for cell overgrowth, iodine may be incorporated in a biodegradable material. The degradation of the biodegradable material may be tracked by means of radio imaging. If, for example, coagulation suppressant therapy is needed during degradation, but only during degradation, the imaging data may indicate whether coagulation suppressant are still needed.
Preferably, the implant comprises at least one discrete marker. Discrete shall be understood as contained to a particular area or location. For example, a discrete marker may be used to designate one side of the implant from the other, or to designate an upper and a lower part. Additionally or alternatively, the discrete marker may be deformable by pressure and indicate a pressure at a particular location of the implant, for example a pressure caused by the adhesive force between a tissue wall and the implant. Particularly preferably, the discrete marker may be a spring that may cause detachment if the adhesion force between the implant and the tissue is below a certain threshold and thus facilitates detection of detachment (similar to predetermined breaking point).
The marker may, in particular, be used to guide a robot, preferably a microrobot, to the implantation site after the implant has been implanted. The marker may define a position in the body and may in particular retain its function for a certain period of time, for example one year. Thus, guiding of a robot may also be done a certain amount after implantation. The marker may be detectable by the robot and thus enable passive guiding. Alternatively, the marker may emit a signal that is detected by the robot and thus enable active guiding.
Preferably, the discrete marker is at least one of radio-opaque and echo-opaque/echogenic. Particularly preferably, the discrete marker is configured as being the radio-opaque element.
The implant may comprise at least two discrete markers that are arranged at a pre-defined distance and/or orientation from one another.
Preferably, the medical implant has a generally flat shape with a first and a second surface, wherein the first and the second surfaces are facing in substantially opposite directions. At least one property of the first surface is different from a corresponding property of the second surface.
The person skilled in the art will understand that “generally flat” may encompass slightly curved flat surfaces and shapes, in particular disk- or chip-like shapes.
The difference between the first and the second surface may be with respect to any measurable quantity, wherein a measurement of said quantity would yield significantly different values. Particularly preferably, the first and second surface differ in polarity, charge, functionalization, surface structure, surface pattern, material, coating, and/or porosity.
The first surface may be adapted to enhance cell ingrowth. In particular, the porosity of the surface may be adapted to allow for cell ingrowth, for example by having a pore size of adapted to allow for cell ingrowth. The pore size may be in the range of a few microns to several hundred microns. Preferably, the pores have a diameter between 50 μm and 500 μm. Additionally or alternatively, the first surface may be biocompatible and in particular be functionalized with growth factors or cell adhesion motifs. The first surface may comprise surface charges that activate and/or attract cells. The first surface may also have a surface roughness adapted to enhance cell ingrowth and/or comprise a velour-like surface.
In particular, at least one of a length, size, and 3D-arrangement of pores and holes may be adapted to enhance cell ingrowth. The length may in particular denominate the longest extension along an axis of a pore or hole in case of nonspherical pores/holes.
Preferably, the first and/or the second surface may comprise or consist of derivates of polymer peptides.
Preferably, the second surface is adapted to provide adhesion to biological tissue. In particular, the biological tissue may be human or animal tissue such as one of endocardial, pericardial and septal tissue. For example, the second surface may comprise a glue layer.
Preferably, at least one surface of the implant, in particular at least one of the first and the second surface of the implant, comprise a velour-like surface. Particularly preferably, all surfaces of the implant comprise a velour-like surface.
Preferably, the adhesive composition is arranged on the medical implant in a pattern. The pattern may be non-uniform. In particular, the pattern may be printed on the implant by inkjet or extrusion printing. The pattern may also be regular, but comprise a 3D structure and/or a non-homogeneous topography.
Preferably, the adhesive composition comprises gelatin-methacryloyl (GelMA), in particular a GelMA of animal original. Particularly suited GelMAs are Fish GelMA, porcine GelMA, and bovine GelMA, i.e. GelMA processed and originating from fish and/or pigs and/or cows. GelMA originating from cold-water fish is particularly suited because of its low-temperature (in particular at room temperature) mechanical flexibility. However, any type of commercially available GelMA is suitable for the invention.
In particular, the GelMA, in particular if derived from pigs, may have a Bloom value of 250 to 325. GelMA derived from fish may not have bloom strength.
Preferably, the GelMA has a molecular weight of 50 to 170 kDa.
Preferably, the GelMA may be formed by a mixture of at least two GelMAs of animal origin. Particularly preferably, the GelMA is formed by a mixture fish GelMA and porcine GelMA.
A mixture of two GelMAs enables to combine properties of different GelMAs. For example, a mixture of (cold water) fish GelMA with porcine GelMA may yield a GelMA with the solubility of porcine GelMA and the mechanical flexibility of fish GelMA. It is also possible to gradually tune properties, for example solubility and mechanical flexibility, by choosing the ratio of different GelMAs, for example porcine and fish GelMA. Such GelMAs are known to the skilled person and commercially available.
Additionally or alternatively, it is also possible to tune properties of the GelMA by varying and/or mixing of different molecular masses.
Preferably, the adhesive composition further comprises at least one photoinitiator. The adhesive composition may comprise several different photoinitiators, a single photoinitiator, or mixtures of different photoinitiators.
The photoinitiator may be a so-called type I photoinitiator, preferably one of lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP, Irgacure, and camphorquinone.
Additionally or alternatively, the photoinitiator may be a so-called type II photoinitiator, preferably one of Eosin Y and mono/di/triethanolamine, Rose Bengal and mono/di/triethanolamine, and Riboflavin and mono/di/triethanolamine.
The GelMA may also be cross-linkable by X-ray radiation. Particularly preferably, the GelMA is cross-linkable via a photoinitiator that can be activated by X-rays. Alternatively, the GelMA may be crosslinkable without a photoinitiator.
The medical implant may also comprise a rivet, in particular a blind rivet. A rivet may be used for attachment of the implant to the tissue.
Rivets are particularly advantageous because they are not sensitive to, and thus securely attach in the presence of, different temperatures, chemical environments, and humidity levels. Preferably, a rivet can thus be used to at least temporarily attach the medical implant to tissue, for example during curing of the adhesive composition, during placement of the implant, and/or while other manipulations on the implant are performed by a medical professional.
The medical implant may comprise at least one retaining element for retaining at least one suture at an outer circumference of the implant. In addition, a suture can be arranged within said loop.
Such a retaining element provides a particularly easy method of temporarily attaching the medical implant to a delivery device. In particular, the suture(s) may provide a connection to the delivery device. Tearing of the suture(s) and/or the retaining element can release the implant.
Preferably, the retaining element comprises or consists of a loop of fabric. Alternatively, the retaining element may also be formed by a backbone folded such as to form a loop in a circumferential area of the implant.
The retaining element may also comprise a pre-determined breaking point.
Preferably, the at least one retaining element is formed from the same material as the medical implant.
Additionally or alternatively, the at least one retaining element is formed of polyurethane with a thickness of 35 to 65 μm. Preferably, the thickness is between 45 and 55 μm.
Alternatively, the at least one retaining element is configured as a separate element arranged on the medical implant. For example, the retaining element may be configured as a separate strip of fabric attached to a circumferential area of the implant and folded such as to form a loop. Alternatively, the retaining element may comprise a loop formed by a suture.
Preferably, the at least one retaining element comprises a predetermined breaking point, particularly preferably an indentation. This allows to control where the retaining element breaks when releasing the implant and as such provides better control the implant procedure.
The adhesive composition may also comprise, in particular consist of, a dried adhesive composition. The dried adhesive composition may swell and/or become at least partially liquid when exposed to a liquid. The dried adhesive composition may also be cross-linkable by exposure to a liquid, such as cyanoacrylate. For example, GelMA as described herein may be dried and used in this manner. Alternatively, any film-forming polymer, particularly biopolymers, such as hyaluronic acid, collagen, heparin and their photopolymerizable counterparts (such as collagen methacrylate) are suitable as well.
The dried adhesive composition is preferably activatable by exposure to a liquid, for example by rehydration in saline, blood, and/or water. Additionally or alternatively, the dried adhesive may also be activatable by exposure to cyanoacrylate. After rehydration, the previously dried adhesive may be curable by exposure to electromagnetic radiation, such as visible and/or UV light, in the presence of a photoinitiator.
Preferably, in the first state, the medical implant comprises a plurality of cavities, in particular micro-sized cavities.
Micro-sized cavities shall be understood as cavities with any shape that have characteristic size in the micrometer range, i.e. from 1 μm to 1000 μm. For example, the medical implant may comprise a plurality of spherical cavities with a diameter of 10 μm to 100 μm. This is particularly advantageous because it ensures a homogenous distribution, and if necessary mixing, of the adhesive composition when it is released.
Preferably, the at least one cavity comprises an additive that, upon exposure to humidity, swells. The at least one cavity may be adapted to release the adhesive composition upon swelling.
This enables a particularly easy way of releasing the adhesive, because exposure to blood automatically makes the cavities swell and thus releases the adhesive.
Preferably, the medical implant comprises at least two different kinds of cavities.
The two types of cavities may be different in size, composition, shape, or any other property. For example, the two different types of cavities may contain different additives that make them swell at different rates. They may also have different wall thickness, different radii, or be made of a different material. They may also be adapted such that one type of cavity swells and the other does not. This enables better control of the release of the adhesive. For example, one component can selectively be released first, or one component can be released at a different rate than the other. It may also enable a better control of the rate of release if the adhesive only comprises one component. For example, it may be advantageous to release a first fraction of the adhesive, and release a second fraction at a later point. It is also possible to adapt the cavities such that they release the adhesive composition or a component thereof at different pressures or temperatures.
Preferably, the at least two different types of cavities are adapted to contain different components of an adhesive composition, in particular in a liquid, gel, dried, or gaseous form. This may, in particular, include any of the features of two different types of cavities as described above. However, it may also include particular properties that enable the storage of a particular component of an adhesive. For example, a certain wall material may be particularly advantageous for one component of an adhesive composition, but may be incompatible with another. Thus, it may be advantageous to adapt the cavities to the specific components of an adhesive composition. Of course, it may also include different sizes or degradation rates of the cavities to account for desired ratios of two components in the final (mixed) adhesive composition.
Preferably, the adhesive composition comprises two components that are individually disposed in the cavities, such that in the first state, the two components are separated. This enables the controlled mixing in the second state, for example at the implant site. This is of course particularly advantageous for two-component adhesives that are not curable before mixing. In this case, unplanned curing before adhesive release, for example by accidental exposure to humidity or elevated temperature can be prevented. However, it is of course conceivable to have an adhesive that comprises one component that only additionally hardens the adhesive composition, for example through cross-linking. It may be advantageous to dispose such a component separately as well.
Preferably, the adhesive composition is adapted to be curable upon mixing of the at least two components. This prevents accidental curing before release of the adhesive. Any curing mechanism to cure the curable adhesive composition after mixing is conceivable. It may be an increase in temperature, exposure to humidity, exposure to electromagnetic radiation such as visible light, infrared light, ultraviolet light, or a combination thereof.
Preferably, the adhesive composition is adapted to spontaneously cure upon mixing of the at least two components. This offers a particularly advantageous way of deploying the adhesive composition because it does not require additional processing steps beyond the release and the spontaneous mixing of the two components. For example, a first component may comprise a primary amine, and a second component may comprise an NHS ester. In the presence of the functional groups of the first and second components, the adhesive may cure upon mixing. However, it is of course possible to combine such an adhesive composition with additional curing mechanisms. For example, an adhesive composition with two components may spontaneously cure upon mixing, but exposure to an additional curing mechanism such as electromagnetic radiation, humidity, or increased temperature may accelerate the curing if necessary. It is also conceivable that a third component is used as an additional hardener.
Preferably, the cavities are adapted to release the adhesive composition upon a temperature increase, in particular to the temperature of a human body. This enables the automatic release of the adhesive composition after implantation because the implant is heated up to 37° C.
Preferably, the cavities are adapted to release the adhesive composition upon exposure to electromagnetic radiation. For example, the cavities may degrade or burst upon irradiation with visible light, infrared light, ultraviolet light, or similar. They may also be adapted to release the adhesive composition upon irradiation with a particular wavelength or wavelength range. If more than one type of cavity is present, they may also be adapted to release the adhesive upon irradiation with different wavelength ranges, such that it is possible to selectively release one component at a time. In general, cavities that are adapted to release the adhesive composition upon exposure to electromagnetic radiation are particularly advantageous because they enable the combination with a delivery device that can transmit light for the release, for example delivery devices as disclosed in WO 15/1756632. It is also a particularly safe way of releasing the adhesive composition because light is typically not prevalent in the human body, thus preventing accidental release.
Preferably, the cavities are adapted to release the adhesive composition upon an increase in pressure. In particular, this enables the release of the adhesive composition upon inflation of a balloon. However, any other mechanism to provide a pressure increase is also conceivable. For example, the cavities may be adapted such that exposure to a liquid causes swelling due to an osmotic pressure that provides a pressure difference. It may also comprise a separate inflation reservoir to provide a pressure on the cavities, the implant, or another part thereof.
Preferably, the cavities are adapted to release the adhesive composition upon a mechanical compression. For example, a compression by a balloon of a delivery device may be employed and is particularly advantageous because delivery devices with balloons are known and thus easy to implement.
Preferably, the adhesive composition is adapted to be curable by exposure to electromagnetic radiation. This provides the similar advantages already described in the context of cavities that are adapted to release upon exposure to electromagnetic radiation. For example, the adhesive composition may be curable upon irradiation with visible light, infrared light, ultraviolet light, or similar. It may also be adapted to be curable upon irradiation with a particular wavelength or wavelength range. In general, adhesive compositions that are adapted to release the adhesive composition upon exposure to electromagnetic radiation are particularly advantageous because they enable the combination with a delivery device that can transmit light for the release, for example delivery devices as disclosed in WO 15/1756632. It is also a particularly safe way of curing the adhesive composition because light is typically not prevalent in the human body, thus preventing accidental curing.
Preferably, the medical implant comprises a self-expanding support structure. A support structure may be any structure with a higher mechanical stiffness and/or strength than the rest of the implant. For example, it may comprise at least one strut of a polymeric material that provides mechanical stiffness to the implant. Additionally or alternatively, it may also comprise a structure that holds the medical implant in place at a desired implant location such as a PFO. For example, it may comprise structure that is adapted to be placed in a defect and hold two patches—one on each side of the defect. Alternatively, it may also only hold one patch. The self-expanding property of the support structure enables particularly easy deployment through a catheter. For example, it may be made of a shape memory material such as a shape memory polymer or a shape memory metal such as a Nitinol. It is also conceivable, however, to use an elastic material that is compressed in a delivery device and expands into its original shape at the implant site.
Preferably, the cavities are formed by closed capsules. In particular, the cavities may be formed by spherical capsules. They may be adapted to be opened by the activation mechanism.
Preferably, the capsules are adapted to break open by the activation mechanism. They may be adapted to break open by any of the activations described herein, for example exposure to electromagnetic radiation, increased pressure, increased temperature, or a combination thereof.
Preferably, the capsule walls are adapted to dissolve by the activation mechanism. This is particularly advantageous if they are adapted to dissolve upon exposure to water, blood, or another bodily fluid, because such an activation mechanism does not require additional handling or processing due the natural presence of these fluids at the implant site. Thus, this provides a particularly easy and safe way of release the adhesive composition from the capsules.
Preferably, the capsule, in particular the capsule wall, comprises a filler material. Filler materials can increase the mechanical strength of the cured adhesive. Thus, such capsules can serve a double purpose by holding the adhesive composition and upon release provide a filler material.
Preferably, the medical implant comprises a porous foam and, in the first state, an adhesive composition is disposed in the porous foam. Of course, it is possible to combine a foam with other cavities as described herein. For example, the medical implant may comprise cavities that are larger than the pores of the foam and contain a second component of the adhesive, a hardener, or another substance. A foam shall, in particular, be understood as a material that substantially consists of pores separated by pore walls made of a solid or a liquid component. The pores of a foam typically exhibit sizes and shapes that fluctuate statistically. Typically, they also percolate.
In a particularly preferred embodiment, the medical implant comprises a braided structure that supports the porous foam.
Preferably, the porous foam comprises solid walls.
Preferably the porous foam comprises walls formed of a hydrogel. Hydrogels are particularly advantageous because they are typically biocompatible. In addition, they can be manufactured from a wide variety of different materials and can thus be adapted to the application or even the patient to be treated. In addition, hydrogels can functionalize and comprise active components. Hydrogels can also be adapted to biodegradable.
Preferably, the pore size of the foam is adapted to allow for cell ingrowth. This facilitates the formation of tissue in or around the foam. In particular, this is advantageous in combination with biodegradable materials such as a hydrogel that is adapted in this way. The medical implant can then be adapted to degrade at a rate that is slower than cell ingrowth. Thus, the medical implant can serve as a template or scaffold and be degraded in the body once the implant is replaced with body tissue.
Preferably, the medical implant comprises at least one reservoir, and at least part of the adhesive composition is disposed in said reservoir. A reservoir shall be understood as a compartment in the medical implant with a characteristic size in the order of magnitude of the implant itself. It may be disposed as a cavity in the medical implant. However, it may also be arranged as a separate reservoir that is attached to the implant. For example, it may be a blister on a surface of the medical implant. A reservoir can be advantageous if a relatively large amount of adhesive needs to be released fast, and/or it is only needed at a specific location.
Preferably, the medical implant comprises at least one separate inflation reservoir. This allows for localized inflation and thus release of an adhesive disposed in a cavity or reservoir. For example, it is possible to inflate a reservoir in a particular location of the medical implant first, releasing a first portion of the adhesive. The rest of the adhesive can then be released at a second point in time. Similarly, it would be conceivable to arrange two inflation reservoirs to selectively release two portions at, for example, two different locations separately.
In a particularly preferred embodiment, the at least one reservoir filled with adhesive is adapted to release said adhesive upon inflation of the at least one inflation reservoir. The medical implant thus comprises at least one reservoir which is at least partially filled with adhesive and at least one inflation reservoir. However, it is of course also possible for the medical implant to comprise several inflation reservoirs and/or several reservoirs filled with adhesive. In particular, one inflation reservoir may be used to release the adhesive from more than one reservoir filled with adhesive. Similarly, two or more inflation reservoirs may be adapted to release the adhesive from one reservoir filled with adhesive. This can provide additional safety through redundancy, or can also be used to provide an easy way to release a defined first and second portion of the adhesive from one reservoir.
Preferably, the reservoir is adapted such that the adhesive is only released on one side of the medical implant. In particular, it may only be released on a distal side of the patch, or on a proximal side of the patch. However, it is also conceivable that the adhesive would be released only on a side wall side of the medical implant. This ensures proper placement of the adhesive facing the tissue and prevents release of adhesive where the medical does not and is not designed to be in operative contact with tissue. As a consequence, the necessary amount of adhesive composition is also reduced. This is more economical and safer for the patient. The medical implant may adapted to only release the adhesive on one side by selecting different materials on each side, by varying the thicknesses and/or the density of the material on each side, by varying the pores size and/or structure of a foam, or by changing any other property that may change the permeability of the implant material for an adhesive composition.
Preferably, the medical implant comprises at least one microchannel in fluid connection with the reservoir for the release of the adhesive. A microchannel shall be understood as a channel with a longitudinal shape that is in fluid connection to a surface of the medical implant and has a diameter that is small compared to the size of the medical implant and the reservoir.
In particular it may have a channel diameter in the range of 1 to 1000 μm, preferably 25 to 750 μm, even more preferably 50-300 μm. Such microchannels enable an easy release of the adhesive composition from the reservoir.
In a particularly preferred embodiment, the medical implant is adapted to only release the adhesive composition on one side of the implant and comprises at least one microchannel. In particular, the implant may be adapted such that the adhesive is only released through said microchannel. Thus, the arrangement of the microchannels provides an easy way of adapting the medical implant to release the adhesive in a particular location, for example only on one side of the implant.
Preferably, the adhesive composition is disposed as fibers, in particular solid fibers. Even more preferably, the adhesive composition comprises at least two components, at least one of which is disposed as solid fibers. Solid fibers may comprise a dried adhesive, or an adhesive that can be molten (such as a hot melt), or an adhesive that swells if exposed to humidity or water. In particular, an adhesive composition may also be disposed as a coating on a fiber.
In particular, at least one of the fibers can comprise an aldehyde that is adapted to adhere to tissue.
[30] Preferably, the adhesive composition is adapted to at least partially dissolve upon exposure to a liquid, in particular one of an organic solvent, a saline, and blood, and form a gel, in particular a hydrogel.
Preferably, the adhesive composition comprises at least one component from the group of methacrylated gelatin, methacryloyl-substituted tropoelastin, poly(acrylic) acid, and methacrylated collagen. Poly(acrylic) acid may be used with a diacrylate/dimethacrylate/amide crosslinker
Preferably, the adhesive composition comprises a dried component that is adapted to be curable by a curing mechanism upon exposure to a liquid, in particular an organic solvent or blood. This is particularly advantageous because it allows for an automatic activation of the adhesive upon implantation due to the presence of blood. Of course, it is also possible to adapt the adhesive composition such that only a selective activation by an organic solvent is possible. It may also be adapted such that exposure to blood activates the adhesive, but an additional exposure to an organic solvent accelerates the activation process.
In particular, it is also possible to adapt the adhesive such that it can be activated by a liquid either inside the body of outside the body before implantation.
In particular, the adhesive composition may be activatable by rinsing with a solution comprising a photoinitiator. Alternatively, the photoinitiator may also be comprised in a dried adhesive and become activated by exposure to a liquid. For example, it may only be reactive in an at least partially swollen adhesive and be kinetically hindered in the dried solid adhesive.
Preferably, the medical implant comprises a scaffold made of bioabsorbable or biodegradable material (hereinafter, reference to “biodegradable” materials shall be understood as encompassing both, bioabsorbable and biodegradable materials), in particular a woven, knitted, electrospun, melt spun, and/or nonwoven bioabsorbable material, and/or a biological implant made by 3-D printing. A scaffold may in particular be used to facilitate cell in-growth and tissue formation.
The invention also relates to a method for deploying a medical implant that comprises and adhesive. The method is particularly advantageous in combination with a medical implant as described herein, but of course it is possible to perform the method with any other medical implant that comprises an adhesive. The method comprises the steps of deploying the medical implant to a first site in a first state, bringing the medical implant into a second state by means of an activation mechanism, and curing the adhesive by means of a curing mechanism. The first site is preferably the implant site. However, it is also possible to bring the implant into the second state either outside the body or inside the body, but not at the implant site.
Preferably, the method comprises a step of increasing the temperature of the medical implant to bring it into the second state. In particular, an increased temperature may be used to release an adhesive as described herein, for example by breaking open capsules and/or dissolving cavities.
Preferably, the temperature increase is at least partially provided by and external heat source. It may also be provided only by an external heat source.
Alternatively or additionally, the temperature increase is at least partially provided by a patient's body heat. It may also be provided only by the patient's body heat.
Alternatively or additionally, the temperature increase is at least partially provided by electromagnetic radiation, in particular infrared light. It may also be provided only by electromagnetic radiation.
Preferably, the method comprises a step of applying a pressure to bring the implant into the second state. For example, the applied pressure may squeeze the adhesive composition out of capsules or cavities. It may also release the adhesive composition from the pores of a foam.
Preferably, the pressure increase is at least partially caused by osmotic pressure. It may also be only caused by osmotic pressure. For example, the adhesive composition may comprise a concentration of ions that is higher than the one of blood and may be comprised in a plurality of cavities with a wall through which water can diffuse. Due to osmotic pressure, water diffuses into the cavities. The cavities can be adapted such that they burst at pressures lower than the osmotic pressure. Of course, the same can be achieved with only one or any other number of cavities.
Preferably, the pressure increase is at least partially caused by applying mechanical deformation, in particular a mechanical pressure, to the implant. The person skilled in the art will of course understand that all the possibilities of increasing the pressure described herein can be combined.
Preferably, the method comprises the step of exposing the implant to humidity to bring it into the second state. Humidity may, for example, cause the dissolution or bursting of cavities or capsules. It may also cause swelling of an adhesive composition to bring it into a curable or cured state. Any other mechanism of releasing the adhesive and/or bringing into a curable state described herein is conceivable.
Preferably, the method comprises the step of exposing the medical implant to electromagnetic radiation to bring into the second state. The electromagnetic radiation may be infrared light, ultraviolet light, or visible light. It may cause degradation of cavities or any other mechanism described herein to release and adhesive from a cavity and/or bring it into a curable state.
Preferably, the method comprises the step of spontaneous mixing of two components in the second state, which causes curing of the adhesive. For example, the adhesive composition may comprise two components that are released from separate capsules by any of the mechanisms herein. Upon release, the mix spontaneously mixes due to the loss of the separation in the cavities. The adhesive composition may thus be adapted such that the two components react with each other without any other external trigger. This provides a particularly easy way of curing the adhesive composition. However, it would of course be possible to combine such an adhesive composition with an additional curing mechanism to cure or harden it further.
Preferably, the method comprises the step of exposing the medical implant to electromagnetic radiation in the second state, which causes curing of the adhesive.
Preferably, the method comprises the step of inflating a separate inflation reservoir to bring the implant into the second state. In particular, inflating of the separate inflation reservoir may squeeze the adhesive out of a reservoir containing the adhesive.
Preferably, the method comprises the step of disposing a liquid to bring the implant into the second state. The liquid may be an organic solvent, in particular an organic solvent that is miscible with human blood. The liquid may, however, also comprise or even consist of water, in particular a physiological saline solution.
The invention is further directed at a medical implant. The medical implant comprises at least one tear line that is arranged in proximity to a circumference of a medical implant. The medical implant is adapted to repair or close a defect, preferably an opening in a ventricular or atrial or vessel wall. In particular, the medical implant may be a patch or any other implant as disclosed herein. The medical implant is further adapted such that, upon deployment to an implant site, in particular a septal defect site, the medical implant can be attached to a tissue wall and torn along the tear line.
A tear line shall be understood as any sort of weakening in the material that creates a site of predetermined failure. Thus, if a mechanical stress is applied to the material, the material will first break along the tear line. This allows for an attachment of the medical implant to a delivery device and easy release from the delivery device by breaking or tearing along the tear line. The tear line may, for example, be a weakening of the material by aligned holes or perforations in the material, or be a lower thickness along a certain line, or a region of a different material.
The tear line may be arranged around a complete circumference of the medical implant, or only at selected regions where the implant is attached to a delivery device. In particular, the medical implant may also comprise elongated elements for attachment to a delivery device and that are detachable from the medical implant by means of a tear line. For example, such elongated elements may be flaps or arms of the same material as the implant, or struts of another material such as a polymer or a metal.
A preferred way of tearing the tear line is by inflation of a balloon on a delivery device. Thus, the tear line is preferably arranged such that a mechanical stress can be applied to it by means of a balloon. For example, the medical implant may comprise tearable flaps that are too short to reach around the circumference of a balloon. Thus, the tear lines would be arranged perpendicularly to the longitudinal axis of the flaps. Inflation of the balloon causes a mechanical stress along the longitudinal axis of the flaps and thus rupture along the tear line.
Preferably, the medical implant comprises a biodegradable material that is adapted to lose its mechanical strength in a human body within three years, preferably twelve months, even more preferably six months. Loss of mechanical strength shall in particular encompass molecular weight loss of a polymeric substance which reduces the mechanical stiffness.
Preferably, the medical implant is coated with a non-adhering coating, in particular silicone and/or poly(tetrafluoro ethylene), between an outer edge and the tear line. This prevents adhesion of the medical implant to tissue in areas that are designed to be retracted with the delivery device.
Preferably, the medical implant comprises a cut, in particular a cross-shaped cut, that is adapted such that a delivery device can partially extend through said cut. The cut may have any shape that provides an opening in the medical implant that can be closed. For example, it may also be a semi-circular cut that forms similarly shaped flap, or a square-shaped cut. Even a linear cut is conceivable, but would have to be long enough for a delivery device to extend through it. In addition, the cut is adapted such that the opening formed by it at least has a tendency to close itself. This allows for the delivery device to at least partially extend on both sides of the implant during delivery, but to be retracted through the medical implant after delivery. After retraction, the flaps close the opening.
Preferably, the medical implant comprises fibers, in particular woven, spun, or knitted fibers. This is particularly advantageous if the medical implant comprises, or consists, of a fabric patch. The fibers can be adapted for certain functions, such as being coated with an adhesive or a drug and/or being biodegradable. Of course, it is possible to combine different types of fibers in one medical implant, for example fibers coated with different adhesive, adapted to biodegrade at different rates, or to elute different drug, or any combination of those.
Preferably, the fibers are made of a biodegradable material.
Preferably, the biodegradable material is selected from a group of poly(lactic-co-glycolic acid), poly(L-lactic acid, poly(D-lactic acid), poly(glycolic acid), poly(caprolactone), any copolymer and/or blend of these materials. These materials are particularly advantageous in that they are non-toxic, well-known and approved for medical applications, and easily commercially available.
Preferably, the medical implant comprises a spine structure. In particular, the spine structure may have different mechanical properties from the rest of the medical implant. For example, it may be made from a different material, or have different dimension such as a greater thickness. The spine structure allows for tuning of the implant properties with more flexibility because the mechanical properties can be tuned without necessarily changing the implant material that may have been selected due to other properties.
Preferably, the spine structure comprises, particularly preferably consists of, a polyurethane.
Preferably, the spine structure extends beyond the medical implant to provide non-elastic tear arms. The non-elastic tear arms can be used to connect the implant to the delivery device, in particular a center lumen. This enables a more reliable implant, in particular patch, release without constraining the choice of material.
Particularly preferably, the retaining element for retaining at least one suture is formed by or on the non-elastic tear arm.
It is also possible to configure the non-elastic tear arms as an extension of the implant, for example by cutting out an implant including extending flaps from a sheet of implant material.
Preferably, the medical implant comprises an adhesive composition, in particular an adhesive composition that is adapted to attach the medical implant to human tissue. In particular, any adhesive composition as described herein may be used. It may preferably comprise glutaraldehyde for pre-treatment of the tissue to which the medical implant is to be attached. In particular, the adhesive composition may comprise derivates of a polymer with linkers that covalently bind to cell surface molecules. Additionally or alternatively, the adhesive composition may include growth factors, chemotactic factors, coagulation or anticoagulation factors, and/or anti-inflammatory compounds incorporated into it.
Preferably, the tear line comprises a laser-cut tear line. This provides a particularly easy and precise way of manufacturing a medical implant with a tear line.
Preferably, the medical implant comprises at least one extension that radially extends beyond the periphery of the medical implant. This allows for attachment to a delivery device.
In a particularly preferred embodiment, the medical implant comprises at least one extension that radially extends beyond the periphery of the medical implant and a spine structure. In particular, the spine structure may also comprise non-elastic tear arms as described herein, wherein the non-elastic tear arms are arranged such as to be comprised in the extension.
Preferably, the at least one extension comprises a string and/or a suture. In particular, the extension may consist of a string and/or a suture. This is particularly advantageous because it provides a simple way of attaching the medical implant to a delivery device, for example by means of a knot or a suture.
Additionally or alternatively, the at least one extension comprises a strip consisting of the same material as the medical implant. This is particularly easy to manufacture because the medical implant can be, for example, cut from the base material with the extension directly.
The retaining element for retaining at least one suture may be formed by the at least one extension.
Preferably, the at least one tear line is adapted, in particular located and dimensioned, such as to separate the at least one extension from the medical implant upon tearing. If the medical implant comprises a spine structure with non-elastic and/or non-extensible tear arms, the tear line may also be arranged such as to weaken the non-elastic tear arms at the same or a different location as the at least one extension.
Preferably, the extensions are adapted to hold the medical implant, preferably a patch, to a delivery device, in particular balloon comprised in a delivery device.
Preferably, the implant is formed by a part of a surface of an inflatable balloon of a delivery device. The balloon may be made of an implant-grade material such as polyurethane. It may also comprise a tear line that is adapted to break at a predetermined pressure or pull force. In particular, the tear line may be formed by a weakening of the material other than holes or cuts to allow for efficient inflation. For example, a circumference of the balloon may have a thinner wall such that the balloon ruptures along said tear line. The balloon, or an area inside a tear line, may also be coated with an adhesive.
The invention is further directed to a delivery device to deliver a medical implant comprising a tear line as described herein, in particular a medical implant comprising an adhesive. It comprises a shaft with an implant holder for holding the implant.
The implant holder is adapted to hold the implant, preferably at least partially, along its periphery. In particular, it may hold the implant by means of an adhesive ring on the periphery of the medical implant. The delivery device further comprises and actuation mechanism for increasing a distance between at least two predefined points of the implant such that upon actuation of the actuation mechanism, said tear line is at least partially ruptured.
Preferably, the actuation mechanism includes an inflatable balloon.
The delivery device, in particular the implant holder, may have a retention element for a suture. The retention element is adapted to retain at least one suture connected or connectable to the medical implant.
A retention element is in particular adapted be in operable connection, i.e. to hold, implants that comprise a retaining element with a suture.
Preferably, the delivery device comprises a gauge, particularly preferably arranged on a handle, for indicating an adhesion force between the medical implant and a tissue.
The indicated adhesion force may be measured by the delivery device directly, for example be pulling a part of the implant and measuring a force. If the implant detaches, which could be detected by a sudden dislocation, the force could be determined. Alternatively, the applied force could be measured without detaching, which would provide a minimum value for the adhesion force.
Alternatively, it is also possible that the gauge indicates a value determined by a marker, for example a marker which is deformable under pressure, on the implant.
The invention is further directed to a medical implant, preferably a patch, preferably a medical implant as described herein, in particular a medical implant adapted to close a defect, preferably an opening in a heart wall, in particular an atrial, ventricular and/or septal wall, or vessel wall, or any other defect as described herein. The medical implant comprises at least one connecting element, in particular a bead, that is located at the outer edge of the medical implant. The connecting element has a size that is larger than a size, in particular a thickness, of the implant such that the connecting element is adapted to be brought into engagement with a delivery device having an appropriate counter element for a connection with said connecting element.
Preferably, the beads comprise a polymeric or metallic material. In particular, they may entirely consist of a polymeric or metallic material. They may be attached to a wire or a suture.
The invention is further directed at a delivery device for a medical implant, in particular a medical implant comprising a connecting element as described herein. The delivery device comprises at least one tube comprising an actuation element. The actuation element may, in particular, be a wire located within said tube. It further comprises at least one holder, preferably at least two holders, that are in operative connection with said actuation element, in particular attached to said wire. The tube and the at least one holder, preferably the at least two holders, are adapted such that a medical implant is held by the at least one holder in a first state. The medical implant can be released by actuation of the actuation element.
The invention further relates to a method of producing a medical implant, preferably a medical implant as described herein. An adhesive composition is at least partially liquid and is arranged on at least one surface of the medical implant. The adhesive composition is dried.
The adhesive composition may be dried subsequently to its arrangement on the implant, or may be dried first and then arranged on the implant.
In particular, the adhesive composition may be dried under a vacuum, or at least a pressure lower than atmospheric pressure. Additionally or alternatively, an elevated temperature may also be employed for drying the adhesive composition.
The invention further relates to a method of producing a medical implant, preferably a method as described above. The method is preferably used to produce a medical implant as described herein. At least one extension element is arranged at an outer circumference of the medical implant. The extension element preferably comprises a pre-determined breaking point. The at least one extension element is configured to form a retaining element. To this effect, an end of the extension element may in particular be arranged on a surface of the medical implant such that the extension element forms a substantially closed loop. The end of the extension element is bonded such as to fix the extension element in a configuration comprising a retaining element. Preferably, the method further comprises the step of arranging a suture in the retaining element, in particular in the substantially closed loop.
The substantially closed loop may in particular be formed by folding of the extension, for example such as to arrange two ends of the extension in proximity to each other and bonding the two ends together.
Bonding is preferably achieved by application of a glue/adhesive composition. Additionally or alternatively, bonding may also be achieved by welding, soldering, casting, and/or mechanical attachment (rivets, hooks, Velcro, stitching).
Preferably, the adhesive composition is arranged on the medical implant via inkjet or extrusion printing.
In particular, inkjet or extrusion printing enables complex structures and patterns of adhesive to be arranged on medical implants that may otherwise be difficult to achieve due to brittleness of the adhesive composition upon drying.
Alternatively, it is also possible to arrange a continuous film of adhesive, wherein a pattern is created with a stamp while the adhesive is in a liquid state.
Particularly preferably, the adhesive composition is arranged in a pre-defined pattern such as to enable flexibility of the implant in certain directions. For example, the adhesive composition may be arranged as slices of a round disk. The implant may then be flexible along the axes separating the individual slices. Additionally or alternatively, the pre-defined pattern may include spikes, pyramids, triangles, cubes, barbs, quills, or other shapes.
The pre-defined pattern may be a two-dimensional pattern, i.e. a substantially flat adhesive film with a patterned structure. Alternatively, the pattern may also be three-dimensional, i.e. also comprise a pattern along an axis perpendicular to the implant surface on which the adhesive composition is arranged.
A three-dimensional pattern is particularly advantageous as it allows for local tuning of pressure. For example, a pyramid that extends from the surface may be pressed against tissue with a higher local pressure than a flat film. Such structures may thus also enhance tissue integration through diffusion into the tissue.
The invention further relates to a method of treating a defect, in particular an opening in a ventricular or atrial or vessel wall. The method comprises a step of implanting a medical device, preferably a medical device as described herein. The implant comprises an adhesive composition. The adhesive composition may be hydrated in situ. Alternatively, the adhesive composition may be hydrated prior to delivery by flushing.
Hydration may be passive, i.e. via liquid water and/or vapour that is naturally present in blood or other bodily fluids, or may be active, i.e. via delivery of a liquid, for example through a fluid canal in the delivery device.
The invention further relates to a method of treating a defect, in particular an opening in a ventricular, atrial, septal, or vessel wall. The implant is preferably an implant as disclosed herein, in particular an implant comprising a retaining element. Preferably, a delivery device as described herein is used to perform the method, preferably a delivery device comprising a retention element. The method comprises the steps of implanting the implant, and pulling at least one suture. The medical implant is released by pulling the suture.
In the following, the invention is described in detail with reference to the following figures, showing:
As shown in
In
The patch 5 is made of electrospun fibers of Dacron and is not biodegradable. However, it would of course be possible to adapt the patch 5 to be biodegradable as well. The layer 28 comprising the reservoirs 16 for the adhesive is of solid Dacron.
It will of course be understood by the person skilled in the art that the embodiments described herein are examples are not restrictive to the scope of the invention. In particular, the different features described herein may be freely combined with other features and/or used without certain features.
It will be understood that any particular pattern of adhesive may be arranged on a patch, in particular if the adhesive is inkjet printed. Alternatively, extrusion printing may also be employed.
It will be understood that a digital gauge may also be used to show a qualitative measure and/or an analog gauge may be used to show a numerical value.
Any of the implants and adhesives disclosed herein are suitable to be patterned with the method shown in
The arm 126 was bonded onto the fabric of the implant 1 by heat bonding wherein the polyurethane was partially molten and diffused into the fabric, thus providing adhesion. The folded arm 126 forms a passage 124 through which a suture is passed. The folded arm 126 thus forms a retaining element and is held by a suture 125. The suture is adapted in its mechanical strength (i.e. thickness and material choice) such that pulling of the suture may tear the arm 126 of the spine structure 31 at the indentation 127. The implant further comprises a radio-opaque element 106, configured as a platinum particle, held on the implant 1 by the folded arm 126. As an alternative to platinum, iridium is also suited as a material for a radio-opaque marker. Additionally or alternatively, the spine structure 31 could be made from a polymer filled with radiopaque agents, such as BaSO4.
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/IB2019/001058 | Sep 2019 | IB | international |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/075550 | 9/11/2020 | WO |
