Patent Application
20200205986
This invention relates to implantable tissue repair devices and methods of manufacturing implantable tissue repair devices. In particular, but not exclusively, the invention relates to implantable tissue repair devices which comprise solvated structural components such as hydrogels and which are adapted to be at least partly inserted into cavities or apertures within a tissue, or which are secured adjacent to said tissue. The invention further relates to methods of repairing, replacing or augmenting tissues, especially cartilaginous tissue.
Cartilage in the adult mammalian body occurs in three principal forms: hyaline cartilage; white fibrocartilage; and yellow elastic cartilage. Hyaline cartilage is chiefly present as articular cartilage in the synovial diarthroidal joints e.g. the knee, hip and shoulder, and between long bones, where it forms the stiff and smooth articulating surfaces. White fibrocartilage is present in the menisci of the knee and temporomandibular joint of the jaw and in intervertebral discs. Yellow elastic cartilage gives support to the epiglottis, Eustachian tube and external ear.
Three pathological conditions involving cartilage damage are very common: osteoarthrosis of articular cartilage; injury to the fibrocartilage of the knee menisci; collapse, rupture or herniation of the intervertebral disc; and damage caused by rheumatoid arthritis. Osteoarthrosis is caused by the progressive damage and breakdown of articular cartilage commonly in the ankle, hip, shoulder and knee (and in many other joint types including elbow, fingers etc.) and is an important cause of pain and reduced mobility in young and old people alike. Injury to the fibrocartilage of the meniscus is a common sports injury and is also seen as a result of road traffic accidents and other traumatic injuries.
Articular cartilage is highly specialized to provide a relatively frictionless, highly lubricated, wear resistant surface between relatively rigid bones. It also functions to transmit and distribute the forces arising from loaded contact to the surrounding cartilage and underlying subchondral trabecular bone. It is a nonvascular connective tissue largely composed of a fluid phase consisting principally of water and electrolytes interspersed in a solid phase containing type II collagen fibrils, proteo-glycan and other glycoproteins. The latter constituents surround, and are secreted by, highly specialized mesenchymal cells, the chondrocytes, which account for some 10% of the volume of articular cartilage. The collagen fibrils within articular cartilage are arranged in a complex arcade structure forming columns arranged normal to and anchored in the osteochondral junction. These columns run up through the deep layer of cartilage, but the predominant fibre orientation gradually changes to form the arches of the arcade structure in the superficial cartilage. In the superficial layer which abuts the joint space, the meshwork of collagen fibrils is much denser while the fibrils are almost entirely tangential to the cartilage surface. The orientation of collagen in articular cartilage is vital to its mechanical function. Healthy articular cartilage is strong and stiff (modulus between 1 and 20 MPa).
No wholly satisfactory procedure exists for replacing damaged articular cartilage in osteoarthrosis and instead in the case of the two most frequently injured joints, the hip and knee, and also other joints such as elbows, shoulders, ankle and extremities, artificial prostheses are most commonly used to replace the entire joint. While these increase mobility and reduce pain they suffer from progressive wear, mechanical failure, adverse tissue reactions and loosening at their interphase with the bone. Accordingly, there has been much work around the area of providing a suitable implantable repair material with improved performance over the currently available prostheses.
One such device is described in WO 2007/020449 A2, describing a cartilaginous tissue repair device with a biocompatible, bioresorbable three-dimensional silk or other fibre lay and a biocompatible, bioresorbable substantially porous silk-based or other hydrogel partially or substantially filling the interstices of the fibre lay.
International patent application number PCT/IB2009/051775 (published under WO2009/133532 A2) discloses a silk fibroin solution and method that can be used to make an improved fibroin material that has been found to be efficient as an implant for cartilage repair. The method for the preparation of the regenerated silk fibroin solution comprises the steps of: (a) treating the silk or silk with an ionic reagent comprising aqueous solutions of one or more of ammonium hydroxide, ammonium chloride, ammonium bromide, ammonium nitrate, potassium hydroxide, potassium chloride, potassium bromide or potassium nitrate; (b) subsequently drying the silk or silk cocoons after treatment of the silk or silk cocoons with the ionic reagent; and (c) subsequently dissolving the silk or silk cocoons in a chaotropic agent.
Furthermore, International patent application number PCT/GB2009/050727 (published under WO2009/156760 A2) discloses method for the preparation of an implantable material for the repair, augmentation or replacement of bone from a fibroin solution. The method comprises: preparing a gel from fibroin solution; preparing a material by subjecting the gel to one or more steps of freezing and thawing the gel, wherein the step of preparing the gel from the fibroin solution is performed in the presence of phosphate ions. The material is generally treated with calcium ions to form a fibroin-apatite. A further method step comprises the step of treating the material with an isocyanate to form cross-links. The implantable material has been found to be efficient as an implant for bone repair.
Whilst implantable cartilaginous tissue repair devices of the prior art are all useful in the repair, augmentation or replacement of damaged cartilage, many such devices suffer from a number of problems, such as: a) failure to anchor securely to existing bone or cartilage; b) failure to integrate with existing bone or cartilage; c) failure of the devices after implantation due to wrinkling, warping or shrinking of the devices over time, or through loosening of the device from its anchor; and d) failure of the device to maintain its overall shape under load within or on the repaired tissue.
In particular many devices suffer from difficulties in effectively and permanently securing the devices to bone, cartilage or other tissue. It is therefore an aim of embodiments of the present invention to provide an implantable repair device capable of load bearing and with improved or enhanced abilities to integrate with, or to be secured to, existing bone or cartilage. It is another aim of embodiments of the present invention to provide an implantable repair device adapted to provide improved articulation of the joint following cartilage replacement.
It would also be advantageous to provide an implantable tissue repair device with improved anchoring in apertures or cavities formed within bone or cartilage, and with improved resistance to any anchoring of the device being torn or detached from the device and/or the aperture or cavity within the bone or cartilage.
It would furthermore be advantageous to provide a device which is flexible under load but which is relatively resistant to permanent shape change, such as wrinkling, warping and shrinking, after fully implanting the device within or on damaged tissue.
It would also be advantageous to provide a device which overcomes or mitigates at least one problem of the prior art described herein.
According to a first aspect of the invention there is provided an implantable tissue repair device for the repair, replacement or augmentation of a tissue, the device comprising a biocompatible and solvated structural material, wherein at least a part of the structural material is in a compressed and/or dried state.
The device therefore comprises an, initially or previously solvated structural material in which at least a part of the material has been compressed and/or dried such that the dimensions of said part are smaller than the same previously uncompressed and/or solvated part. In embodiments wherein the material has been compressed, it will be appreciated that the material is a compressible material.
In preferred embodiments, the part or parts are both compressed and dried. It is particularly effective to firstly compress the part of the material and then dry the part while compression is still applied to the part; this then allows compressed dimensions to be maintained, even when the compressive force is removed, whilst maintaining the original shape of the part (albeit with smaller dimensions due to compression). Compression of the part or parts reduces the dimensions of the part/parts without moving said part/parts from their original positions on or in the device, while subsequence drying (especially freeze-drying) maintains the part or parts with reduced dimensions. When the part or parts are re-solvated and decompressed, they do not move relative to their original positions on or in the device, and instead decompress back to larger dimensions in the same place.
The device may comprise a body comprising the structural material and may further comprise one or more anchoring elements projecting from the body (and arranged in use to anchor or secure the device to bone, cartilage or other biological tissue). The body and anchoring elements may comprise the same structural material. At least part of the body may be compressed and/or dried. The anchoring elements or a part thereof may be compressed and/or dried. In some embodiments both the body and the anchoring elements are compressed and/or dried.
In preferred embodiments substantially only the anchoring elements or a part thereof are compressed and dried, but in some embodiments both one or more parts of the body and at least part of the anchoring elements are compressed and dried.
It will be appreciated that the part or parts of the device that is compressed and/or dried is in a compressed and/or dried state for use of the device, and which may subsequently be decompressed and/or re-solvated (and wherein the solvent may be the same or different to the original solvent present in said part or parts) during or after implantation in or adjacent to a tissue.
Compression or drying of the part or parts may comprise reducing the width or diameter and/or the circumference or perimeter thereof. In some embodiments, the part or parts may be reduced in two dimensions, while in other embodiments the dimensions may be reduced in three dimensions. The reduction in dimensions may reduce the volume of the part or parts. In some embodiments, substantially the whole device may be compressed and/or dried, and thus substantially the whole device may have one or more reduced dimensions compared to the uncompressed and/or solvated device. Compression and/or drying of the anchoring element or elements may comprise reducing one or more dimensions of the, or each, anchoring element, especially reducing the width, diameter, circumference and/or perimeter thereof.
The anchoring elements may comprise a projection extending from a main body of the device. The projection may comprise a tubular projection or any other suitable shape, such as a keel, a flange or the like, arranged in use to be located in an aperture, slot or cavity in, or adjacent to, a tissue to be repaired, replaced or augmented. There may be two or more anchoring elements, arranged in use to be located in shaped holes, slots or cavities in or adjacent to a tissue. In preferred embodiments, the dimensions of any hole, slot or cavity in a tissue are smaller than the fully uncompressed and/or dried part/parts of the device; in this way, when the compressed and/or dried part or parts is inserted into the hole, slot or cavity and re-swelled or decompressed to its original dimensions, the part or parts will form a tight interference fit within the hole, slot or cavity.
The part or parts of the device which are compressed or dried may have dimensions no more than 98%, 97%, 96%, 95%, 90%, 80%, 75%, 70%, 65%, 60%, 55% or 50% of the part's or parts' original (uncompressed and/or non-dried) volume, dimensions, circumference, perimeter and/or height. In some embodiments, the part (or parts) is between 60% and 75% of its uncompressed or non-dried volume, dimensions, circumference, perimeter and/or height. Preferably there are two or more anchoring elements and each anchoring element is compressed and/or dried such that each element is between 60% and 75% of its original volume, dimensions, circumference, perimeter and/or height.
In embodiments in which the part(s) is dried the part(s) may be partially dried or substantially fully dried. In embodiments in which the part(s) is compressed, the part(s) may be partially compressed or fully compressed to the extent of its elasticity.
The structural material of the device may comprise a material selected from silk fibroin, fibrin, fibronectin, cellulose, alginate, hyaluronic acid, gelatin and collagen, for example. In preferred embodiments, the structural material comprises silk fibroin. The silk fibroin may be a regenerated silk fibroin and the silk fibroin may be regenerated mulberry, wild or spider silk fibroin. The structural material is preferably a hydrogel and the hydrogel may comprise any of the aforesaid materials, especially silk fibroin or collagen.
The solvent of the solvated structural material may comprise water or an aqueous solvent. In such embodiments, all references to “drying” and “dried” may be considered to be dehydration or dehydrating. In other embodiments, the solvent may be another biocompatible solvent such as ethanol, for example; however, in preferred embodiments the solvent is water or an aqueous medium.
The device may comprise one or more fibres, or one or more network of fibres located at least partially within the structural material. The network of fibres may comprise a two-dimensional or three-dimensional network of fibres. Suitable two dimensional networks include a mesh, net or web. The network of fibres may include at least one fibre network layer. Suitable three-dimensional networks include a plurality of stacked fibre layers, for example.
The or each fibre network may comprise wound or woven or knitted or embroidered or stitched or braided or knotted fibres, or compressed felts or fabric layers (such as cloth layers).
The fibres may be formed from a biocompatible fibre material which may be selected from silk, cellulose, alginate, gelatin, fibrin, fibronectin, collagen, hyaluronic acid and chondroitin sulphate. In preferred embodiments, the fibres comprise silk fibres. Silk fibres may be derived from mulberry, wild or spider silk, for example. In some embodiments, the fibres may comprise a synthetic material, such as a polymeric material. Suitable polymeric materials may be selected from polyester, polyethylene nylon, polylactic acid, polyglycolic acid (or other species of the polyhydroxyalkanoate family) or mixtures or derivatives thereof. In alternative embodiments, the fibres may be ceramic, metal or alloy fibres, for each. Each fibre in the fibre network may comprise the same material, or some of the fibres may comprise different materials. For example, some fibres may be silk fibres and other fibres may be polyethylene fibres. In some embodiments, each fibre may comprise two or more of the aforementioned materials; for example a fibre may comprise silk and polyethylene, and different materials may be located along the length of the fibre, such as a silk middle and polyethylene ends, for example.
The fibres or fibre network may be partially dissolved in the structural material of the device, such that an outer surface of the fibres substantially blends, melds or merges into the structural material. This forms a stronger, reinforced body, increasing the strength of the device.
At least one fibre or fibre layer may be present in each anchoring element. In some embodiments, where the device comprises a body from which the anchoring elements project, both the body and anchoring elements may comprise at least one fibre or fibre network. In some embodiments both the body and the anchoring elements comprise a separate fibre layer or at least one fibre of the fibre network of the anchoring elements may project from the fibre network of the body of the device.
The fibres may be compressible. In such embodiments when the part of the structural material is compressed and/or dried, and the dimensions of the part or the whole of the device are reduced, the fibres may also compress or contract. The fibres may then decompress or expand upon decompression or re-solvation/swelling of the structural material.
In some embodiments, the device comprises a body formed of the structural material from which project a plurality of integrally formed anchoring elements; and the body and anchoring elements comprise fibre layers. The fibre layer in the anchoring elements may be stitched to the fibre layer in the body via one or more threads. The threads may comprise any suitable biocompatible thread or suture materials, such as polyester, nylon or the like for example, and may comprise suture threads.
The threads may be configured to bend or concertina within the structural material when the part or whole of the structural material is compressed and/or dried and the part or whole of the structural material is shrunk. In this way the threads may maintain their relative positions within the device during compression and/or drying of the structural material.
The structural material of the device may additionally comprise a rigid support such as a plate or framework embedded or otherwise located within the structural material. The rigid support may reinforce the structural material and aid in maintaining structural integrity and load-bearing of the device. The rigid support may be positioned within the structural material such that it is not exposed or does not protrude from the material when the part or whole of the material is compressed and/or dried. The rigid support may therefore be set in from any external surfaces of the structural material (or device) at a distance which ensures it is not exposed or does not protrude from the surfaces after compression and/or drying of the structural material.
The structural material may be a porous material. The porous material may comprise an open porous network comprising a network of inter-connected pores.
The device or the body of the device preferably comprises a shape substantially corresponding to a tissue part in need of repair, replacement or augmentation.
The device or the body of the device may comprise the shape of part of a meniscus, such as the meniscus of a knee joint; a part of articular cartilage; or a disc (for the replacement of a cartilaginous disc, e.g. an intervertebral disc), for example.
According to a second aspect of the invention there is provided a method of manufacturing an implantable tissue repair device for the repair, replacement or augmentation of a biological tissue, the method comprising providing a device comprising a biocompatible solvated structural material, and compressing and/or at least partially drying at least a part of the structural material to reduce one or more dimensions of the at least part of the device.
The method may comprise retaining the device in the compressed and/or at least partially dried or dehydrated state until use.
If the method comprises compressing at least part of the device, the method may comprise securing the compressed part in the compressed state, for example by binding the compressed part in a biocompatible and biodegradable binding material. Such a material may comprise polylactide, polyglycolide or polylactide-polyglycolide material, for example.
In some embodiments, the method comprises dehydrating or drying at least part of the structural material. Dehydrating or drying the structural material has the advantage that the structural material, in its solvated state, has already assumed the final shape of the part of the device and drying may shrink the part in the same overall shape and configuration. Subsequent rehydration will decompress or relax the hydrogel back to its original shape, thereby retaining the original (pre-compressed, pre-dried) architecture of the device.
In other embodiments, the method comprises compressing at least part of the device followed by freezing at least the compressed part. In such embodiments, the freezing of the part maintains the part in the compressed state.
In preferred embodiments, the method comprises firstly compressing at least a part of the device to reduce at least one dimension of the device, and subsequently drying at least the compressed part either during or after compression. This ensures that the part or parts of the device is first compressed to smaller dimensions, then dried to prevent decompression of the part or parts when the compression force on the device is removed, thereby eliminating the need for any outside means of maintaining the part or parts in the compressed state.
In particularly preferred embodiments the part or parts of the device (especially the anchoring elements) is/are compressed to reduce at least one dimension, and the compressed part is freeze-dried, to ensure that the part or parts maintains the original shape and configuration of the solvated, uncompressed part; and which can then be re-solvated to relax/decompress or reswell the compressed part back to its original (or substantially original) dimensions.
In the dehydrated state, the part of the device, or the device per se, may be immersed or packaged in a solvent-free medium, in order to ensure the device remains in the dried state. The device may be stored in the solvent-free medium until just before use. The device may be packaged in a solvent-free gas, such as in nitrogen, for example.
The device may comprise a body and may further comprise one or more anchoring elements (arranged in use to anchor the device to bone, cartilage or other biological tissue) and the method may comprise compressing and/or drying at least part of the body and/or the anchoring element or elements. Compression and/or drying of the anchoring element or elements may comprise reducing one or more dimensions of the, or each, anchoring element, such as reducing the width, diameter, circumference and/or or perimeter thereof.
The compression and/or drying of at least part of the structural material is reversible and therefore, in use, the device may be inserted into an aperture, cavity or the like, in a tissue to be repaired, replaced or augmented such that the reduced dimension part may be easily located in the aperture, cavity or the like and then the compression and/or shrinkage of the part can be reversed by decompression and/or re-solvation; such that the dimension(s) of the part increase, substantially fill the aperture, cavity or the like and the part then tightly grips the aperture or cavity wall to provide a secure anchorage. The part inserted into the aperture or cavity may be configured such that decompression or re-solvation causes the part to expand or relax back to dimensions greater than the aperture or cavity, and due to the resilient nature of the structural material from which it is made, will resiliently grip the wall or walls of the aperture or cavity, thereby significantly decreasing the chance of the part being removed from the aperture or cavity in use.
The anchoring elements may comprise a projection extending from a main body of the device. The projection may comprise a tubular projection or a projection comprising any other suitable shape (such as a keel, wedge, ridge or the like, for example), arranged in use to be located in an aperture, slot or cavity in or adjacent to a tissue to be repaired, replaced or augmented. There may be two or more projections, arranged in use to be located in holes or cavities in or adjacent to a tissue.
In preferred embodiments, the or each anchoring element is compressed then dried, and compression may be maintained during drying.
The part or parts of the device which are compressed and/or dried may be shrunk to no more than 98%, 97%, 96%, 95%, 90%, 80%, 75%, 70%, 65%, 60%, 55% or no more than 50% of part's or parts' original (uncompressed or non-dehydrated) volume, width, diameter, circumference and/or perimeter, and optionally length/height. In some embodiments, the part (or parts) is shrunk to between 60% and 75% of its uncompressed or non-dried volume, dimensions, circumference, perimeter and/or height. Preferably there are two or more anchoring elements comprising tubular projections and each anchoring element is compressed and dried to shrink the element to between 60% and 75% of its original volume, dimensions, circumference or perimeter.
The method may comprise at least partially drying the whole device or the whole structural material of the device, such as the structural material forming the body and anchoring elements.
Drying of the part or whole of the device may comprise freeze drying the part or whole of the device. In order to ensure the structural material does not crack or deform during freeze-drying, the device or part thereof may be immersed or contacted with a lyo-protectant during freeze-drying to protect the part from stresses and replace part of the solvent lost through drying. Suitable lyo-protectants include saccharides such as trehalose and sucrose, polymers such as polyvinylpyrrolidone or polyvinyl alcohol, glycerol or other poly-ols, for example. Glycerol may be preferred due to its ability to soften the dried structural material during and after freeze drying. Treatment with a lyo-protectant, such as glycerol, may be performed before drying or freeze-drying, while the structural material is in its solvated state. The use of a lyo-protectant is particularly useful for hydrogel materials (as the structural material). The use of a lyo-protectant is also particularly useful for structural material, such as hydrogels, containing pores, especially containing an open porous network of inter-connected pores, as the lyo-protectant may penetrate the pores and provide lyo-protection from both within and without the device during drying or freeze-drying.
In preferred embodiments, the part of parts of the solvated structural material is compressed and frozen in the compressed state.
In particularly preferred embodiments, the method may comprise compressing the solvated structural material followed by drying the compressed structural material, especially compressing, freezing and drying, such as by compressing, freezing and freeze-drying. In some embodiments, the method comprises compressing part or the whole of the device followed by drying the part or whole of the device. In such embodiments, drying is preferably performed by freeze-drying as discussed and defined herein. Compression of the part or whole of the device may be as described hereinabove and the part or whole of the device is preferably shrunk to between 50% to 80% of the size of the solvated part or device. In preferred embodiments, the device comprises a body and a plurality of anchoring elements and at least the anchoring elements are compressed and dried. In some embodiments, substantially only the anchoring elements are compressed and dried. In preferred embodiments only the anchoring elements are compressed and the whole of the body and anchoring elements (or the whole device) is dried.
The structural material may comprise a material selected from silk fibroin, fibrin, fibronectin, cellulose, alginate, hyaluronic acid, gelatin and collagen. In preferred embodiments, the hydrogel comprises silk fibroin. The silk fibroin may be a regenerated silk fibroin and the silk fibroin may be regenerated mulberry, wild or spider silk fibroin.
The solvent of the solvated structural material may comprise water or an aqueous solvent. In such embodiments, all references to “drying” and “dried” may be considered to be dehydration or dehydrating. In other embodiments, the solvent may be another biocompatible solvent such as ethanol, for example; however, in preferred embodiments the solvent is water or an aqueous medium.
The method may comprise locating at least one fibre, or a network or layer of fibres at least partially within the structural material. The fibres or network or layer of fibres may be as described herein above. The network of fibres may comprise a two-dimensional or three-dimensional network of fibres. Suitable two dimensional networks or layers include a mesh, net or web. The network of fibres may include at least one fibre network layer. Suitable three-dimensional networks include a plurality of stacked fibre layers, for example.
The fibres or fibre network may be partially dissolved in the body of the device, such that an outer surface of the fibres substantially blends, melds or merges into the structural material. This forms a stronger, reinforced body, increasing the strength of the device.
The solvated structural material may be a hydrogel, which may be formed by gelling a hydrogel precursor solution. The hydrogel precursor solution may comprise a solution of monomer, dimers, oligomers or polymers in a suitable solvent. The fibres, fibre network or fibre layer may be located within the precursor solution before gelling of the solution.
In embodiments, wherein a part of the structural material is compressed and/or dehydrated, and the dimensions of the part or the whole of the device are reduced, the fibres may also compress or contract. The fibres may then decompress or expand upon decompression or rehydration of the hydrogel.
In embodiments, wherein the device comprises a body from which project a plurality of integrally formed anchoring elements and the body and anchoring elements comprise fibre layers, the fibre layer in the anchoring elements may be stitched to the fibre layer in the body via one or more threads. The threads may comprise any suitable biocompatible thread materials, such as polyester, nylon or the like for example, and may comprise suture threads.
The threads may be configured to bend or concertina within the structural material when the part or whole of the structural material is compressed and/or dehydrated and the part or whole of the structural material is shrunk. In this way the threads may maintain their relative positions within the device during compression and/or dehydration of the structural material.
The method may comprise locating a rigid support such as a sheet or framework within the structural material. The rigid support may be positioned within the structural material such that it is not exposed or does not protrude from the structural material when the part or whole of the structural material is compressed and/or dehydrated. The rigid support may therefore be set in from any outer surfaces of the structural material (or device) at a distance which ensures it is not exposed or does not protrude from the surfaces of the compression and/or dehydration of the structural material. The rigid support may be located within the structural material precursor solution before gelling.
The dried or dehydrated material may be adapted to substantially re-solvate or rehydrate over a time period of between 30 second and 60 minutes when placed in a solvent environment of tissue into or onto which the device has been implanted, and in some embodiments between 1 minute and 30 minutes or between 2 minutes and 10 minutes.
According to a third aspect of the invention there is provided a device of the first aspect of the invention made by the method of the second aspect of the invention.
The device may be stored in a container until use. The container may comprise an inert and/or non-aqueous medium such as nitrogen gas or the device may be vacuum-packed. The container may be airtight. The container, medium and device may be sterile.
According to a fourth aspect of the invention there is provided a method of securing a device of the first aspect of the invention to or within a tissue, the method comprising the steps of (a) optionally forming an aperture, slot or cavity within or adjacent to the tissue; (b) securing the device to or within the tissue; and (c) decompressing and/or re-solvating the part or parts of the tissue which are compressed and/or dried.
Step (b) may comprise locating the compressed and/or dried parts in an aperture or cavity in the tissue or adjacent to the tissue. In preferred embodiments step (a) comprises forming one or more apertures, slots or cavities in bone adjacent (such as below) the tissue and step (b) comprises locating the compressed and/or dried part or parts in the aperture or apertures in the bone. In other embodiments, the tissue comprises an aperture or cavity therein (which may be as a result of damage to the tissue or formed deliberately in the tissue) and step (b) comprises locating the compressed and/or dried part or parts of the device in the aperture or cavity of the tissue. In such embodiments, the part or parts of the device, when decompressed or re-solvated, serve to substantially plug or fill the aperture, slot or cavity. In some embodiments, the whole device is compressed and/or dried and the whole device is located within the tissue, and subject to decompression and re-solvation serves to plug or fill the aperture, slot or cavity.
The dried and/or compressed part or parts may be dimensioned, in the dried and/or compressed state, to fit into the aperture, slot or cavity in the tissue or the aperture, slot or cavity adjacent to the tissue (such as bone adjacent to the tissue). When the part or parts are then decompressed and/or re-solvated, the part or parts expand in at least one dimension to resiliently grip the inner surface of the aperture, slot or cavity. In this way, an implantable tissue repair device can be used which is both easy to secure to or adjacent to a tissue in need of repair, replacement or augmentation, and without requiring a user to manually compress or distort parts of the device, in situ, to fit into any aperture or cavity, thus reducing the likelihood of damage to the device or tissue. In addition, the decompression and/or re-solvation of the part or parts of the device when located in an aperture or cavity enables the part or parts (or whole device in some embodiments) to resiliently grip the aperture, slot or cavity, and so both reduces the likelihood of the implant being removed or dislocated from the aperture, slot, cavity or tissue, and reduces or eliminates the need for further securement means to be used to secure the implant (such as pins, screws, sutures etc. attached to the implant) or glues, cements or other external elements.
The device may comprise a device of the first aspect of the invention. The device may comprise one or more anchoring elements as described for the first aspect of the invention and the anchoring elements may be compressed or dehydrated. The anchoring elements may be inserted in an aperture, slot or cavity of the tissue or adjacent to the tissue, as described hereinabove.
The dried part or parts may be re-solvated with a biological fluid such as a biological fluid located in the aperture, slot or cavity of the tissue, or which seeps, extrudes or bathes the tissue. The biological fluid may be blood, plasma, synovial fluid, bone marrow or the like, for example. Alternatively, the dried part or parts may be re-solvated by addition of an external aqueous fluid, such as saline, after the part or parts have been secured to or within the tissue.
In preferred embodiments the structural material is a hydrogel and the part or parts of the device are compressed and then dehydrated in order to reduce the dimensions of the part or parts, and decompression occurs as a result of rehydration, which causes re-expansion of the hydrogel through hydration, thereby ensuring decompression or relaxing of the part or parts.
The dried or dehydrated material may be adapted to substantially re-solvate or rehydrate over a time period of between 30 second and 60 minutes when placed in a solvent environment of the tissue into or onto which the device has been implanted, and in some embodiments between 1 minute and 30 minutes, or between 2 minutes and 10 minutes. Re-solvation is preferably effected by the biological fluid present within or around the tissue onto or into which the device has been implanted, and the solvent may, for example, be blood, interstitial fluid, bone marrow, plasma or the like.
According to a fifth aspect of the invention there is provided an implantable tissue repair device of the first aspect of the invention for use in the repair, replacement or augmentation of a tissue.
In some embodiments, the tissue is cartilage.
In some embodiments the devices of the invention comprise bone plugs; anchors; cartilage repair devices; cartilage re-surfacing devices; bone repair devices; tendon or ligament attachment devices; anchoring meniscus horns; muscle repair (including heart) devices; hernia repair devices; gastrointestinal tissues repair devices (e.g. gut wall) vasculature repair devices; nerve repair devices; dura, trachea, or gynaecological tissue repair devices, ophthalmic tissue repair devices, skin repair devices or other epithelial tissue repair devices or other soft tissues repair devices or tissue augmentation or replacement devices for any of the above mentioned tissues.
The implantable tissue repair, replacement or augmentation devices of the invention have a number of advantageous properties and functions, compared to prior art devices, including: easy and rapid insertion into lesions and cavities in tissue; the ability to provide tactile and visual feedback to physicians on correct implantation (such as an indication when any anchoring elements are correctly anchored in apertures); the ability to deliver regenerative material into bone or other tissue due to the type and configuration of the structural material; anchoring elements are integral with any body of the device and so there is no potentially weak junction (which may also pose a hygiene risk); and the fact that the part of parts of the device which are compressed and/or dried can be delivered with said parts in the desired shape to fit any aperture, slot or cavity (but with smaller dimensions), which is particularly useful when in providing anchoring elements which taper outwardly to fit into apertures—the anchoring element can be shrunk to fit through the narrowest part of the tapered aperture and then decompressed and/or re-solvated to increase its dimensions and substantially plug the aperture. In some embodiments, the hole or aperture in the tissue will extend through the tissue completely; and in such embodiments the or each anchoring element may comprise a part such as a distal, free end which in the uncompressed and/or dried state has larger dimensions than the hole or aperture through which it is to be inserted, in use, and wherein the part has dimensions smaller than the hole or aperture when in the compressed or dried state. In this way, the part of the anchoring element may be compressed and/or dried, inserted through the hole or aperture so that the part extends out of the hole or aperture, and then the part may be relaxed/reswelled by re-solvation and/or decompression, such that it assumes its original dimensions which are larger than the hole or aperture through which it was inserted, and the part is prevented from being pulled back through the hole or aperture. Such embodiments may be particularly useful for relatively thin tissues, such as gut wall, for example.
In order that the invention may be more clearly understood one or more embodiments thereof will now be described, by way of example only, with reference to the accompanying drawings, of which:
The body 4 includes a fibre layer comprising a silk fibre mesh 7 extending therethrough. The anchoring elements 6, 6′, 6″ each include a corresponding fibre layer 9,9′,9″ extending therethrough. The fibre layer 7 of the body and the fibre layers 9,9′,9″ are connected via nylon sutures 11,11′,11″ stitched therebetween. The fibre layers 7,9,9′,9″ and sutures 11,11′,11″ serve to provide structural support and load bearing to the device 2.
The device 2 of
The device is processed as follows to achieve the configuration shown in
Use of the device 2 of
The resultant anchorage of the device in the bone surface 14 is shown in
In an example of the embodiment of the device 2 described above, having two anchoring elements 8, 8″, a comparison of the force required to remove the device from corresponding holes 12, 12″ having a diameter of 3.4 mm, in a bone substrate of the knee of a sheep was measured for device 2 with the anchoring elements 8,8″ both compressed and dehydrated to a diameter of 3.2 mm, and then when the anchoring elements were rehydrated to decompress to a diameter of 4.0 mm in the holes (thus being constrained by the diameter of the hole and forced to compress and resiliently grip the inner surfaces of the holes 12, 12″). The force required to remove the compressed and dehydrated anchoring elements 8,8″ (and thus the device) was approximately 0.57N, while the force required to remove the decompressed anchoring elements 8,8″ was approximately 28N (approximately a 49-fold increase in the force required).
Turning now to
The devices 2, 102 of
Use is substantially the same as that described above for the embodiment of the device 2 of
In use of both devices 2, 102, rehydration of the dehydrated parts of the devices may be undertaken by the addition of an aqueous media such as a saline solution to the body and/or anchoring elements; but in preferred embodiments, rehydration will take place due to ingress of biological aqueous media from the surrounding tissues on which, and in which the devices 2, 102 are located; such as blood, bone marrow, interstitial fluid, synovial fluid and the like.
In further embodiments of the device 202, a rigid support framework may be inserted within the body 204 before the hydrogel material is gelled, and the rigid framework may extend into the anchoring element 208, 208′, 208″. Such rigid frameworks ensure further strengthening of the device 202, and the rigid frameworks may be porous, to encourage larger surface area for infiltration by hydrogel material, to increase the grip of the hydrogel material around the rigid framework. Rigid supports may be formed from ceramic, polymeric, metal or alloy material, for example.
In other embodiments (not shown), the bodies or anchoring elements of any devices may be solely compressed, rather than compressed and dehydrated, and may be retained in a compressed configuration by freezing the part(s) in the compressed configuration, or by using a retaining material such as a coating layer of biodegradable or water soluble polymer, for example, which can be applied after compression of the part(s) to keep the part in the compressed (reduced dimensions) configuration. However, in preferred embodiments the bodies and/or anchoring elements of the devices are at least dehydrated, and may be compressed then dehydrated in the compressed state.
Once the device 2 has been placed in position, as shown in
The use of anchoring elements with a part or parts with increased dimensions (pre-compression and/or pre-drying) compared to the remainder of the anchoring elements, especially at the distal end of the anchoring elements, is particularly useful for anchoring devices of the invention into apertures or holes which either taper or extend completely through a tissue; as the part or parts can be compressed and/or dried to reduce its dimensions, then be inserted into the hole or aperture and decompressed or re-solvated to increase the dimensions back to the original dimensions, which traps the anchoring element within the hole.
In further embodiments, the structural material of the device may not be a hydrogel material, but may be a material which is solvated (either by water or another biocompatible solvent), such as a collagen sponge material or a polymeric foam material, for example.
The above embodiments are described by way of example only. Many variations are possible without departing from the scope of the invention as defined in the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1708909.5 | Jun 2017 | GB | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/GB2018/051349 | 5/18/2018 | WO | 00 |
