A DBM SCAFFOLD PRODUCT AND A METHOD OF MANUFACTURING THE SAME

Abstract

A demineralized bone matrix (DBM) scaffold product comprising a plurality of elongate demineralised bone fibres mechanically interconnected with one another in a regular and repeating pattern.

Claims

1. A demineralized bone matrix (DBM) scaffold product comprising a plurality of elongate demineralised bone fibres mechanically interconnected with one another in a regular and repeating pattern.

2. A DBM scaffold product as claimed in claim 1 in which said plurality of elongate demineralised bone fibres are woven together in a regular and repeating weave pattern.

3. A DBM scaffold product as claimed in claim 1 in which said plurality of elongate demineralised bone fibres are knitted together in a regular and repeating knit pattern.

4. A DBM scaffold product as claimed in claim 1 in which said elongate demineralised bone fibres each comprise a single filament taken from a donor bone.

5. A DBM scaffold product as claimed in claim 1 in which said elongate demineralised bone fibres each comprise a composite strip comprising a plurality of filaments taken from donor bones which are connected together by an adhesive.

6. A DBM scaffold product as claimed in claim 5 in which said adhesive comprises a liquid or gel tissue adhesive comprising one or more of a fibrin glue, cyanoacrylate based product, polyethylene glycol-PE-sealant or glutaraldehyde albumin-derived product.

7. A DBM scaffold product as claimed in claim 6 in which said adhesive further comprises a haemostatic component.

8. A DBM scaffold product as claimed in claim 5 in which said filaments comprise flat sides, in which said filaments are arranged with end portions thereof overlapping, and with said adhesive located between said overlapped end portions.

9. A DBM scaffold product as claimed in claim 5 in which said product is formed into a sheet.

10. A DBM scaffold product as claimed in claim 5 in which said product is formed into a three-dimensional shape defining an inner area.

11. A DBM scaffold product as claimed in claim 1 in which said product comprises a plurality of elongate synthetic fibres mechanically interconnected with said plurality of elongate demineralised bone fibres in a regular and repeating pattern.

12. A DBM scaffold product as claimed in claim 11 in which said synthetic fibres comprises one or more of a polylactic acid, polyglycolic acid, collagen or chitosan.

13. A DBM scaffold product as claimed in claim 1 in which said product further comprises a gel or viscous liquid applied to said plurality of elongate demineralised bone fibres.

14. A DBM scaffold product as claimed in claim 13 in which said gel or viscous liquid comprises one or more of glycerol, collagen, gelatin, hyaluronic acid, lecithin, calcium sulphate, poloxamer, calcium phosphate or carboxymethyl cellulose (CMC).

15. A method of manufacturing a DBM scaffold product comprising a plurality of elongate demineralised bone fibres, said method comprising the step of mechanically interconnecting said plurality of elongate demineralised bone fibres with one another in a regular and repeating pattern.

16. A method of manufacturing a DBM scaffold product as claimed in claim 15 in which the step of mechanically interconnecting said plurality of elongate demineralised bone fibres with one another in a regular and repeating pattern comprises weaving the elongate demineralised bone fibres together in a regular and repeating weave pattern.

17. A method of manufacturing a DBM scaffold product as claimed in claim 15 in which the step of mechanically interconnecting said plurality of elongate demineralised bone fibres with one another in a regular and repeating pattern comprises knitting the elongate demineralised bone fibres together in a regular and repeating knit pattern.

18. A method of manufacturing a DBM scaffold product as claimed in claim 15 in which prior to said step of mechanically interconnecting said plurality of elongate demineralised bone fibres with one another in a regular and repeating pattern said method comprises the step of forming each of said elongate demineralised bone fibers by connecting a plurality of filaments taken from donor bones together with adhesive to form a composite strip.

19. A method of manufacturing a DBM scaffold product as claimed in claim 18 in which said filaments comprise flat sides, and in which said step of forming each of said elongate demineralised bone fibres as a composite strip comprises arranging adjacent filaments with end portions thereof overlapping, and locating said adhesive between said overlapped end portions.

20. A method of manufacturing a DBM scaffold product as claimed in claim 15 in which said step of mechanically interconnecting said plurality of elongate demineralised bone fibres with one another in a regular and repeating pattern comprises forming said product as a sheet.

21. A method of manufacturing a DBM scaffold product as claimed in claim 15 in which said step of mechanically interconnecting said plurality of elongate demineralised bone fibres with one another in a regular and repeating pattern comprises forming said product as a three-dimensional shape defining an inner area.

22. A method of manufacturing a DBM scaffold product as claimed in claim 15 in which said method comprises the further step of placing said product into a mould of a pre-determined shape and size and applying a pressure thereto in order to form said product into a pre-determined shape.

Description

[0036] Fourteen embodiments of the invention will now be described by way of example and with reference to the accompanying drawings, in which:

[0037] FIG. 1 is a front view of a first DBM scaffold product according to the first aspect of the present invention;

[0038] FIG. 2 is a front view of a second DBM scaffold product according to the first aspect of the present invention;

[0039] FIG. 3 is a side view of a section of a composite DBM fibre strip used in manufacturing a third DBM scaffold product according to the first aspect of the present invention;

[0040] FIG. 4 is a photograph of a fourth DBM scaffold product according to the first aspect of the present invention;

[0041] FIG. 5 is a photograph of a fifth DBM scaffold product according to the first aspect of the present invention;

[0042] FIG. 6 is a photograph of a sixth DBM scaffold product according to the first aspect of the present invention;

[0043] FIG. 7 is a front view of a seventh DBM scaffold product according to the first aspect of the present invention;

[0044] FIG. 8 is a front view of an eighth DBM scaffold product according to the first aspect of the present invention;

[0045] FIG. 9 is a perspective front view of a ninth DBM scaffold product according to the first aspect of the present invention;

[0046] FIG. 10 is a perspective view of a tenth DBM scaffold product according to the first aspect of the present invention;

[0047] FIG. 11 is a sectional front view of an eleventh DBM scaffold product according to the first aspect of the present invention;

[0048] FIG. 12 is a side view of wound composite DBM fibre strip for use in manufacturing a twelfth DBM scaffold product according to the first aspect of the present invention;

[0049] FIG. 13 is a side view of wound composite DBM fibre strip for use in manufacturing a thirteenth DBM scaffold product according to the first aspect of the present invention;

[0050] FIG. 14 is a sectional front view of a fourteenth DBM scaffold product according to the first aspect of the present invention; and

[0051] FIG. 15 is a diagrammatic view of a method of manufacturing a DBM scaffold product according to the second aspect of the present invention.

[0052] As shown in FIG. 1 a first DBM scaffold product 1 comprises a plurality of elongate demineralised bone fibres 2 mechanically interconnected with one another in a regular and repeating pattern.

[0053] The first DBM scaffold product 1 shown in FIG. 1 represents the first aspect of the present invention in its most basic form. It is not an embodiment which is likely to be practical in isolation in a clinical sense, as it is too small, however it is presented in order to illustrate the essential features of the invention. It comprises 12 individual filaments 3, each of which is a single bone fibre 2 taken from a donor bone according to the method defined in GB1711130.3 in the name of the Applicant. As a result of the use of this method the bone fibres 2 are substantially equal in length, width and depth.

[0054] The bone fibres 2 are woven together in a regular and repeating pattern. Namely, an array of six parallel warp strands 4 are intertwined with an array of six parallel weft strands 5. Each of the warp strands 4 and each of the weft strands 5 passes reciprocally between the warp strands 4 or weft strands 5 normal to it. As such, the first DBM scaffold product 1 is a basic square DBM sheet with a mechanical interconnection pattern which is regular, and which is repeated nine times.

[0055] The first DBM scaffold product 1 has the bone fibres 2 arranged in a relatively spaced relationship with each other, whereas in practice this spacing may be much narrower in order to improve the structural integrity. Also, the first DBM scaffold product 1 does not feature any mechanism to secure the bone fibres 2 along the edges 6. Given its small size it would likely fall apart if manipulated. However, in practice DBM scaffold products would be manufactured which were far larger in size, and which may also feature a seam or other mechanism along the edges to maintain structural integrity. For example, with a woven pattern like that shown in FIG. 1 ends of the bone fibres 2 can be folded back through 180 degree and tucked into the weave.

[0056] In FIG. 2 a second DBM scaffold product 7 also comprises a plurality of elongate demineralised bone fibres 8 mechanically interconnected with one another in a regular and repeating pattern. This time the bone fibres 8 are knitted together in a regular and repeating pattern. In particular the bone fibres 8 are arranged in six rows 9, and each bone fibre 8 is formed into loops 10 which pass around the bases 11 of the loops 10 in the row 9 above. In this manner the rows 9 are entwined together into stitches 12 in order to connect them together and to form a cohesive material sheet.

[0057] As with the first DBM scaffold product 1 second DBM scaffold product 7 is not an embodiment which is likely to have any real application in a clinical sense, as it is too small. However, it is presented in order to illustrate the manner in which the knitted version of the invention can be performed.

[0058] In first DBM scaffold product 1 individual filaments 3 of bone are used, but in order to make larger woven DBM scaffold products, and to make any practical knitted DBM products, the bone fibres need to be longer.

[0059] Therefore, FIG. 3 shows a section of a composite DBM fibre strip 13 for use in manufacturing a third DBM scaffold product (not shown). The composite strip 13 is made up of a plurality of filaments 14 of bone fibre which are connected together by an adhesive 15. The filaments 14 have flat sides 16, and they are arranged with end portions 17 thereof overlapping, and with the adhesive 15 located between the overlapped end portions 17. The adhesive 15 used in this illustrative example is fibrin glue.

[0060] Composite strips like composite strip 13 can be made any length by simply repeating the connections. In this way long composite strips can be formed as strands suitable for weaving or knitting much larger DBM scaffold products than first DBM scaffold product 1 and second DBM scaffold product 7 described above. The same regular and repeating patterns are used, but simply on a larger scale.

[0061] In particular, FIG. 4 illustrates a fourth DBM scaffold product 18 made using composite strips 19 like composite strip 13. In this case fourth DBM scaffold product 18 was made using a basic single row crocheting method to produce an elongate shape. The regular and repeating pattern therefore only extends along one axis. It will be appreciated that this method can be continued to make DBM scaffold products like this of any length.

[0062] FIG. 5 illustrates a fifth DBM scaffold product 20 also made using composite strips 21 like composite strip 13. In this case fifth DBM scaffold product 20 was made using a basic multiple row crocheting method to produce a sheet, which has a regular and repeating pattern which extends along two axes. It will be appreciated that this method can be continued along either axis to make DBM scaffold products of any length and width.

[0063] FIG. 6 illustrates a sixth DBM scaffold product 22 also made using composite strips 23 like composite strip 13. In this case sixth DBM scaffold product 22 was also made using a basic crocheting method to produce a larger cohesive mass, which has a regular and repeating pattern which extends along two axes.

[0064] In the photographs shown in FIGS. 4 to 6 the regular and repeating pattern of the knitting technique used is not clearly visible due to the flexible nature of the composite strips 19, 21 and 23. In particular, the fourth, fifth and sixth DBM scaffold products 18, 20 and 22 are generally resilient and maliable, and do collapse and distort in shape. However, in each case the particular mechanical interconnection between the composite strips 19, 21 and 23 remains at all times. Namely, the manner in which the composite strips 19, 21 and 23 intertwine between one another in rows of stitches is always maintained.

[0065] FIG. 7 shows a seventh DBM scaffold product 24 which is made using the same weaving technique as employed in the first DBM scaffold product 1, but using composite strips 25 like composite strip 13. As such, it is larger in size. It also has seams 26 at the edges 27 formed by the composite strips 25 being woven back into the weave. The seventh DBM scaffold product 24 has been formed as a square sheet for clinical applications which would require such an application of DBM fibres. The seventh DBM scaffold product 24 can be applied as a sheet, for example to the surface of a bone, or it can be rolled or folded up into suitable other three dimensional shapes for application in any inter bone location where bone regrowth is required. A particular advantage which can be achieved is to orientate the seventh DBM scaffold product 24 with the warp strands thereof bridging an inter bone gap, and the weft strands providing substantially equally spaced keying points for bone re-growth along that gap.

[0066] FIG. 8 shows an eighth DBM scaffold product 28 which is like the seventh DBM scaffold product 24 described above except it is formed into a circular shape, which may find particular application in certain other clinical procedures. Once again, it has a seam 29 along its edge 30 to prevent the composite strips from becoming detached. The eighth DBM scaffold product 28 can also be applied as a sheet, or it can be rolled or folded up for application.

[0067] FIG. 9 shows a ninth DBM scaffold product 31 which has been made using the same knitting technique as employed in the second DBM scaffold product 7, but using composite strips 32 like composite strip 13. It was created as a sheet, and then closed to make a three dimensional cylinder shape, by means of a knitted seam 33. The ninth DBM scaffold product 31 may find particular application in clinical procedures in which a bone needs to be wrapped in DBM fibres as a surgical technique. The ninth DBM scaffold product 31 can be used a sleeve and placed over such bone.

[0068] FIG. 10 shows a tenth DBM scaffold product 34 which is like the ninth DBM scaffold product 31 described above but it has been formed as a pouch defining an inner area 35. The tenth DBM scaffold product 34 may find particularly beneficial application in certain clinical procedures where different kinds of bone material can be advantageously located in different areas. For example, autograft or allograft bone chips (not shown) can be placed in the inner area 35, and the tenth DBM scaffold product 34 located in the body such that the DBM bone fibres are adjacent the surfaces of bone to be treated, while the larger bone chips inside the product 34 are held in the area between the surfaces to be treated. This is applicable to filling any large bone defects where DBM alone is not sufficient to fill the volume, and is therefore supplemented by the larger bone chips. It can also be used in posterolateral spinal fusion surgery, where there are bone grafts on both sides of the spine and it is known to use bags of bone chips, which are placed specifically to fill the bone defects. However, unlike in the known products where the bags are simply made of biodegradable resorbable mesh, the tenth DBM scaffold product 34 is made from DBM bone fibres which would significantly improve the performance.

[0069] If desired the tenth DBM scaffold product 34 can be closed at the top 36 in order to fully enclose the inner area 35. It is simply a question of using a knitting or seam-making technique to attach one side of the rim 37 to the other. This would capture any autograft or allograft bone chips inside, which may be beneficial for handling prior to implantation, and for when placed inside the body, as the bone chips will not escape.

[0070] In the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above all the composite strips 19, 21, 23, 25, 32 are like composite strip 13, which is made up of bone fibres. However, DBM scaffold products like the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above can also be made using a combination of such composite strips 13 and elongate synthetic fibres mechanically interconnected together in the same kinds of regular and repeating patterns to make the same kinds of shapes of DBM scaffold product. FIG. 11 shows a section of an eleventh DBM scaffold product 38 which is like this. Namely, alternate warp strands 39 are like composite strip 13, while the intervening warp strands 40 are made from synthetic fibre strips. Likewise, alternate weft strands 41 are like composite strip 13, while the intervening weft strands 42 are made from synthetic fibre strips. In this illustrative example the synthetic fibre is collagen.

[0071] The eleventh DBM scaffold product 38 has a greater tensile strength than the DBM scaffold products described above because the synthetic fibre strips 40, 42 are integrally formed and do not feature any connections secured by the adhesive 15. They therefore provide additional structural support to the composite strips 39 and 41.

[0072] In addition to this, the presence of the synthetic fibre strips 40, 42 alters the biodegradation rate of the product 38. It is effectively half that of the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above as it has half the volume of DBM fibres. This may be preferred for various clinical reasons. It will be appreciated how this can be adjusted by controlling the ratio of the composite strips of DBM fibres to the strips of synthetic fibre. For example, every third warp and weft strand can be a synthetic fibre strip, or every fourth strand and so on.

[0073] In the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above the composite strips 19, 21, 23, 25, 32 are like composite strip 13, which is a simplex strand made up of multiple DBM filaments 15 connected to one another in a line. However, DBM products like the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above can also be made using more complex composite strips. FIG. 12 shows such a wound composite DBM fibre strip 43 for use in manufacturing a twelfth DBM scaffold product (not shown). In this illustrative example two composite strips 44 and 45 are like composite strip 13, but they are wound together to make a simplex yarn or rope-like structure, as shown. This can then be used to make the same kinds of woven or knitted shapes of DBM scaffold product as the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above. Such DBM scaffold products would have greater tensile strength than the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above because each wound composite DBM fibre strip 43 is more dense, and because the two composite strips 44 and 45 support each other.

[0074] Alternatively DBM products like the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above can be made using similarly wound strips, but made up of both DBM fibre composite strips like composite strip 13 and synthetic fibre strips. FIG. 13 shows such a wound composite strip 46 for use in manufacturing a thirteenth DBM scaffold product (not shown). Composite strip 47 is like composite strip 13, and strip 48 is made of a synthetic fibre, and they are wound together to make a simplex yarn or rope-like structure, as shown. In this illustrative example the synthetic fibre is chitosan. This wound composite strip 46 can then be used to make the same kinds of woven or knitted shapes of DBM scaffold product as the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above. Such products would have greater tensile strength than the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above because each wound composite DBM fibre and synthetic fibre strip 46 is more dense, and because the synthetic fibre strip 48 provides extra support to the composite strip 47.

[0075] In addition to this, the presence of the synthetic fibre strip 48 alters the biodegradation rate of the end product. It is effectively half that of the fourth to tenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above as it has half the volume of DBM fibres. This may be preferred for various clinical reasons. It will be appreciated how this can be adjusted by controlling the ratio of DBM fibre strands to synthetic fibre strands, by using both wholly wound composite DBM fibre strips like wound composite DBM fibre strip 43 and mixed DBM fibre and synthetic fibre strips like wound composite DBM fibre and synthetic fibre strip 46. For example, in a woven product every second, third or fourth or so on warp and weft strand can be like wound composite DBM fibre and synthetic fibre strip 46.

[0076] In the fourth to thirteenth DBM scaffold products 18, 20, 22, 24, 28, 31 and 34 described above the composite strips of DBM fibre, wound or otherwise, or the wound composite DBM fibre and synthetic fibre strips are used without any of the known additional viscous compounds usually used with DBM scaffold products. It will be appreciated how it would be possible to add such viscous compounds to such DBM scaffold products. In order to illustrate this FIG. 14 shows a sectional front view of a fourteenth DBM scaffold product 49 which is like eleventh DBM scaffold product 38 describe above, but a viscous liquid compound 50 has been added. In this illustrative example the compound is glycerol. Adding the compound 50 makes the fourteenth DBM scaffold product 49 more cohesive as a scaffold and gives it superior handling characteristics.

[0077] As referred to above the second aspect of the present invention is a method of manufacturing a DBM scaffold product. FIG. 15 is a flow diagram illustrating the steps involved in one illustrative example of such a method.

[0078] Namely, in a first step 51 a plurality of elongate demineralised bone fibres are formed, each time by connecting a plurality of filaments taken from donor bones together with adhesive to form a composite strip, like composite strip 13 described above.

[0079] In a second step 52 each DBM fibre composite strip is wound together with a synthetic strip made of chitosan, to form yarn or rope-like strips, like wound composite DBM fibre and synthetic fibre strip 46 described above.

[0080] In a third step 53 the wound composite strips are woven together in a regular and repeating knit pattern to form a square DBM scaffold product like seventh DBM scaffold product 24 described above.

[0081] The method of the second aspect of the invention can end there, if a square DBM scaffold product is required for a particular clinical procedure. However, other steps can be carried out to make the DBM product more suitable for use.

[0082] For example, in a fourth optional step 54 the DBM scaffold product is placed into a mould of a pre-determined shape and size, before pressure is applied to form the product into a pre-determined shape. For example, a plurality of DBM scaffold sheets can be press fitted together to make more dense sheets. These may find particular application in supporting bone fractures by being wrapped around the fracture site.

[0083] Alternatively, the DBM scaffold product is formed into other known implant structures, such as boat like structures which can carry bone chips therein, and which are commonly inserted into the spine in spinal fusion surgery.

[0084] In a fifth option step 55, which could be carried out in isolation, or before or after the fourth optional step 54, a gel or viscous liquid is added to the DBM scaffold product in order to make it more cohesive as a scaffold and give it superior handling characteristics.

[0085] It will be appreciated that the method illustrated in FIG. 15 is merely illustrative, and other steps can be included like those mentioned in detail above. For example, in the third step the DBM product can be formed into a pouch for carrying bone chips. The second step could be omitted so the DBM product was formed only from composite strips of DBM fibres like composite strip 13.

[0086] The present invention can be altered without departing from the scope of claim 1.

[0087] For example, in other alternative embodiments (not shown) more complex weaving patterns are used involving repeated sequences of reciprocation between multiple warp or weft strands. In one such alternative embodiment the weft strands follow a pattern of travelling over two warp strands before travelling under just one, and then repeating.

[0088] In another alternative embodiment (not shown) DBM scaffold products contain different pre-determined ratios of bone fibres to synthetic fibres than those described above, for example 2:1, 3:1 and so on, depending on the desired biological and physical properties that would be achieved.

[0089] Therefore, the present invention provides DBM scaffold products with regular and repeating mechanical interconnection between the fibres. This results in regular performance across the area of the DBM scaffold product because the bone fibres are arranged in the same manner in relation to one another throughout. It also prevents the product from easily deforming or from individual fibres coming loose. It also means that certain two dimensional and three dimensional DBM scaffold product forms can be created by means of the mechanical interconnection method used, which shapes have particular clinical applications. The resulting products are easy to handle, and if flat they can be rolled or folded into more complex shapes depending on the clinical requirement. Depending on the shape and size of the DBM scaffold product it can be used in various surgical procedures such as spinal fusion, bone augmentation, guided tissue regeneration in dental procedures and so on. The product would find particular application in posterolateral spinal fusion where the fibres could be specifically orientated across 2 or 3 lateral spinal processes due to their regular and repeating pattern. This is something which is not possible with any known DBM products in a neat and organised manner. The DBM scaffold product of the present invention is effectively custom made to achieve this.