Abstract
An implantable tissue repair device for the repair, replacement or augmentation of a tissue, the device having a biocompatible solvated structural material, where at least part of the structural material is in a compressed and/or dried state.
Claims
1. An implantable tissue repair device for the repair, replacement or augmentation of a tissue, the device comprising a biocompatible solvated structural material, wherein at least part of the structural material is in a compressed and/or dried state.
2. A device as claimed in claim 1 wherein the part or parts are both compressed and dried.
3. A device as claimed in claim 1 comprising a body and one or more anchoring elements projecting from the body.
4. A device as claimed in claim 3 wherein the anchoring elements or a part thereof are compressed and/or dried.
5. A device as claimed in claim 3 wherein both the body and the anchoring elements are compressed and/or dried.
6. A device as claimed in claim 3 wherein the anchoring elements are integrally formed with the structural material of the body.
7. A device as claimed in claim 1 wherein the structural material is a hydrogel.
8. A device as claimed in claim 1 wherein the part or parts of the device which are in a compressed and/or dried state have dimensions no more than 95% of the part's or parts' original uncompressed and/or solvated state.
9. A device as claimed in claim 1 wherein the structural material comprises a material selected from silk fibroin, fibrin, fibronectin, cellulose, alginate, hyaluronic acid, gelatin and collagen.
10. A device as claimed in claim 1 further comprising a network of fibres located at least partially within the structural material.
11. A device as claimed in claim 10 wherein the fibres in the fibre network are formed from a biocompatible fibre material selected from silk, cellulose, alginate, gelatin, fibrin, fibronectin, hyaluronic acid, chondroitin sulphate, ceramic, metal and alloy.
12. A device as claimed in claim 1 comprising the shape of part of a meniscus, a part of articular cartilage or an intervertebral disc or part thereof.
13. 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.
14. A method as claimed in claim 13 comprising firstly compressing at least a part of the device, and subsequently drying at least the compressed part.
15. A method as claimed in claim 13 wherein the device comprises one or more anchoring elements and the method comprises compressing and/or drying at least the or each anchoring element.
16. A method as claimed in claim 15 wherein the or each anchoring element is compressed and then dried.
17. A method as claimed in claim 13 wherein the part or parts of the device which are compressed and/or dried are shrunk to no more than 95% of the part's or parts' original dimensions.
18. A method as claimed in claim 13 wherein the part or parts of the device are compressed and frozen.
19. A method as claimed in claim 13 wherein drying of the part or whole of the device comprises freeze-drying the part or whole of the device.
20. A method as claimed in claim 18 wherein the structural material is contacted with a lyo-protectant before freezing.
21. A method as claimed in claim 13 comprising compressing the solvated structural material followed by drying the compressed solvated structural material.
22. A method as claimed in claim 13 wherein the structural material comprises a material selected from silk fibroin, fibrin, fibronectin, cellulose, alginate, hyaluronic acid, gelatin, chitin, chitosan and collagen.
23. A method as claimed in claim 13 comprising locating a network or layer of fibres at least partially within the structural material before or during solvation of the material.
24. An implantable tissue repair device for the repair, replacement or augmentation of a tissue, the device made by the method of claim 13.
25. A method of securing a device of claim 1 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 device which are compressed and/or dried.
26. An implantable tissue repair device of claim 1 for use in the repair, replacement or augmentation of a tissue.
Description
DETAILED DESCRIPTION OF THE INVENTION
[0078] 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:
[0079] FIG. 1 illustrates a side cross-sectional view of an embodiment of a device of the invention with all parts in an uncompressed and hydrated state;
[0080] FIG. 2 illustrates a side cross-sectional view of the embodiment of FIG. 1 with the anchoring elements in a compressed and dehydrated state (with the equivalent uncompressed and hydrated dimensions shown in dotted lines);
[0081] FIG. 3 illustrates a side view of a second embodiment of the device of the invention in a compressed and dehydrated state;
[0082] FIG. 4A illustrates a side cross-sectional view of the device of FIGS. 1 and 2 in place in a lesion in cartilage, with the anchoring elements in a compressed and dehydrated state;
[0083] FIG. 4B illustrates a side cross-sectional view of the device of FIGS. 1 and 2 in place in a lesion in cartilage, with the anchoring elements in a decompressed and rehydrated state;
[0084] FIG. 5A illustrates the device of FIG. 3 in place in a lesion in cartilage with the device in a compressed and dehydrated state;
[0085] FIG. 5B illustrates the device of FIG. 3 in place in a cartilage lesion, in a decompressed and rehydrated state;
[0086] FIG. 6 illustrates a side sectional view through a third embodiment of a device of the invention with the anchoring elements in a decompressed and dehydrated state;
[0087] FIG. 7A illustrates a perspective view of another embodiment of a device of the invention with the anchoring elements in a compressed and freeze-dried state, spanning a tear in gut wall; and
[0088] FIG. 7B illustrates the device of FIG. 7A in spanning the gut wall, with the anchoring elements in a decompressed and rehydrated state.
[0089] FIG. 1 illustrates a side view of an implantable tissue repair device 2 of the first aspect of the invention. The device 2 includes a device body 4 and a number of anchoring elements 6, 6, 6. The anchoring elements 6, 6,6 are integrally formed and project from the body 4. Both the body and the anchoring elements are formed from a structural material comprising a silk fibroin hydrogel which is both stiff and resilient. The device 4 is suitable as a device for the repair of articular cartilage; for example, it may be inserted into a tear, lesion or other cavity within damaged articular cartilage.
[0090] 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.
[0091] The device 2 of FIG. 1 is in a fully hydrated and uncompressed state. FIG. 2 illustrates the same device 2 in which the anchoring elements 6, 6, 6 have been firstly compressed, and then dehydrated to maintain the anchoring elements 6. 6, 6 in a compressed state. As can be seen from FIG. 2, the anchoring element 6, 6, 6 in their compressed and dehydrated state have shrunk such that both the diameter and volume of the anchoring element 6, 6, 6 are less than the fully hydrated and non-compressed state. The compressed and dehydrated anchoring elements are shown with reference numerals 8, 8, 8.
[0092] The device is processed as follows to achieve the configuration shown in FIG. 2. After compression of the anchoring elements 8, 8, 8 to reduce their diameter and volume, the whole device 2, including the body 4 undergoes freezing and then freeze-drying. The compression force may then be removed, and the anchoring elements 8, 8, 8 are maintained with reduced dimensions due to the freeze-drying dehydration. Importantly the overall shape of the device is maintained after freeze-drying, with only the anchoring elements having reduced dimensions but also having the same shape as the uncompressed and hydrated anchoring elements.
[0093] Use of the device 2 of FIG. 2 will now be described with reference to FIGS. 4A and 4B. The device 2 is inserted into a cavity formed into articular cartilage. The articular cartilage is connected to a bone surface 14. The articular cartilage has a cavity bounded by an articular cartilage wall 10, 10, as shown in FIG. 1. The bone surface 14 is prepared by a practitioner drilling cavities 12, 12, 12 into the bone surface 14, as shown in FIG. 4A. In this configuration, the articular cartilage wall 10, 10 bounds a cavity through which the bone surface 14 is accessible, and in which the holes 12, 12, 12 are also accessible. In use the body 4 of the device 2 is lowered into the cavity formed between the cartilage walls 10, 10 until the lower side of the body 4 rests against the upper bone surface 14. In this position, the compressed and dehydrated anchoring elements 8, 8, 8 project into the holes 12, 12, 12 in the bone surface 14, as shown in FIG. 1. The compressed and dehydrated anchoring elements 8, 8, 8 are dimensioned such that they are narrower than the dimensions of the holes 12, 12, 12. The reduced dimensions and rigid, stiff properties of the compressed and dehydrated anchoring elements ensures that they can be easily and quickly inserted into the holes in the bone surface 14, without requiring undue manipulation and providing tactile feedback to the practitioner that they have been correctly inserted into the holes, which ensures that damage to the anchoring elements 8, 8, 8 and body 4 is mitigated or eliminated. Once in position, as shown in FIG. 4A, the anchoring elements 8, 8, 8 are rehydrated, which causes expansion and decompression of the elements such that they substantially fill the holes 12, 12, 12 in the bone surface 14, as shown in FIG. 4B. Rehydration can be caused by addition of an aqueous media such as saline, but it is preferred for rehydration to occur naturally as biological fluid (such as blood, synovial fluid, plasma, bone marrow etc.) and accompanying cells, nutrients and factors in the environment of the cartilage and bone seeps into the device 2, body 4, anchoring elements 8, 8, 8 and holes 12, 12 and 12. In fact, the anchoring elements 8, 8, 8 are arranged to expand or rehydrate such that their dimensions are slightly larger than the dimensions of the holes 12, 12, 12. The resilience of the hydrogel material of the anchoring elements 8, 8, 8 ensures that on complete rehydration, they resiliently grip the inner surfaces of the holes 12, 12, 12, to secure the device 2 to the bone surface 14 and cartilage 10, 10.
[0094] The resultant anchorage of the device in the bone surface 14 is shown in FIG. 4B, where it can be seen that the anchoring elements 8, 8, 8 completely fill the holes 12, 12, 12.
[0095] 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).
[0096] Turning now to FIG. 3, a second embodiment of a device 102 of the invention is shown. The device 102 includes a body 104 formed from a silk fibroin hydrogel. The body 104 includes a number of anchoring elements 108, 108, 108 projecting from the bottom surface of the body 104, as shown in FIG. 3. The device 102 shown in FIG. 3 is entirely compressed and dehydrated from its original uncompressed and hydrated state. Shown in dotted lines are the original dimensions of the original body 4 and anchoring elements 6,6, 6. Thus, it can be seen that the entire device 104 shrinks in both thickness and area compared to the uncompressed and hydrated state.
[0097] The devices 2, 102 of FIGS. 2 and 3 have been dehydrated via freeze-drying to preserve the shape of the body and prevent further shrinkage. This has the advantage that the position of the anchoring elements 6, 106 doesn't change when moving between the hydrated and dehydrated states, only the dimensions change. Both devices 2, 102 may be immersed in a lyo-protectant prior to and/or during freezing. Suitable lyo-protectant materials include saccharides such as trehalose and sucrose, polymers such as polyvinyl alcohol, glycerol or other polyols. Once the device or part thereof has been dehydrated it may then be further stored in a moisture free environment or immersed in an inert material such as nitrogen gas, in order to ensure that the device or part thereof does not rehydrate inadvertently before use. Use of the device 102 of FIG. 3 is illustrated in FIGS. 5A and 5B.
[0098] Use is substantially the same as that described above for the embodiment of the device 2 of FIG. 2. FIG. 5A illustrates the device 102 located on the bone surface 14 within a cavity formed in articular cartilage, bounded by cartilage walls 10, 10. The bone surface 14 has a number of holes 12, 12, 12 drilled therein, as described above in relation to FIGS. 4A and 4B. As can be seen from FIG. 5A, the body 104 of the device 102 is dimensioned such that in the dehydrated state, the outer periphery is spaced apart from the cartilage walls 10, 10. In addition, the anchoring element 108, 108, 108, in their dehydrated state, have a perimeter less than the perimeter and length of the holes 12, 12, 12. Upon rehydration of the device 102, both the body 104 and the anchoring elements 108, 108, 108 expand to fill both the cavity between the surfaces of the articular cartilage 10, 10 and the holes 12, 12, 12. As with the device 2 described hereinabove, the device 102 is adapted such that expansion of the body 104 and anchoring elements 108 creates a device with dimensions slightly bigger than that of the cavity formed between cartilage walls 10, 10 and holes 12, 12, 12; and the resilience of the hydrated hydrogel forming the body 104 and anchoring elements 108 ensures that the device 102 securely grips both the cartilage walls 10, 10 and the holes 12, 12, 12.
[0099] 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.
[0100] FIG. 6 illustrates a third embodiment of a device 2 of the invention. The device 202 includes a body 204 formed of a silk fibroin hydrogel, from which extend a number of integral anchoring elements 208, 208, 208, which are also formed from the same material as the body 204. As with the devices described for FIGS. 2 and 3 above, the anchoring elements 208, 208, 208 are compressed and dehydrated, and thus have shrunken dimensions (periphery and volume) compared to the rehydrated anchoring elements (which are shown in dotted lines). In the embodiment of the device 204 shown in FIG. 6, the body includes a fibre mesh layer 220 which extends across the entire extent of the body 204. The fibre layer 220 is formed of silk fibres and the silk fibres are woven into a mesh-like structure. The mesh-like structure includes gaps between the fibres, through which the hydrogel of the body 204 infiltrates and surrounds. In addition, the anchoring elements 208, 208, 208 also include a fibre mesh layer 222, 222, 222, respectively. In the embodiments shown in FIG. 6, the fibre layers 220, 222 of the body 204 and anchoring elements 208 respectively serve to further strengthen the device 202 to enable it to withstand load pressure, and to reduce the chance of tearing or damage to the hydrogel material. The silk fibres of the fibre layers 220, 222 are also biocompatible and ensure that the device 202 has an environment conducive for infiltration of cells and other cellular material in to the device 202 after implantation. The silk fibres are also resistant to damage caused by dehydration and rehydration of the anchoring element 208.
[0101] 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.
[0102] 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.
[0103] FIGS. 7A and 7B illustrate perspective views of a further embodiment of a device 2 of the invention, located on and spanning left 310 and right 310 sections of a torn ovine gut wall. The device 2 of FIGS. 7A and 7B comprises a silk fibroin body 304 which includes a silk fibre mesh layer 307 extending therethrough. The body 4 includes two anchoring elements 306,306 extending therefrom and which are located to protrude through holes drilled through the left gut wall section 310 and right gut wall section 310. The anchoring elements include a plurality of sutures 311 and 311 extending therethrough and stitched to the silk fibre layer 307 of the body 304.
[0104] FIG. 7A illustrates the device 2 positioned over the tear between the left and right gut wall sections 310,310, with compressed and freeze-dried anchoring elements 306, 306 having a smaller diameter than the uncompressed and hydrated elements. The compressed and freeze-dried elements 306, 306 have a circumference slightly less than the holes through which they are inserted, for ease of insertion through the holes.
[0105] Once the device 2 has been placed in position, as shown in FIG. 7A, the anchoring elements 306,306 begin to reswell due to ingress of bodily fluids such as blood, mucus and the like. FIG. 7B shows the anchoring elements 306, 306 when fully reswelled, and take the shape of a thinner shaft 312, 312 from which protrudes a disc-shaped head 313, 313 having a larger circumference than the shaft 312, 312. It can be seen from FIG. 7B that the heads 313,313 of the anchoring elements 306, 306 has a circumference greater than the shafts 312,312 and the holes within the gut wall sections 310,310, such that the body 304 of the device 2 cannot be pulled away from the sections 310,310 due to the heads 313,313 being too large to fit through the holes in the gut wall sections 310,310.
[0106] 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.
[0107] 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.
[0108] 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.
