Synthetic osteochondral composite and method of fabrication thereof

• US 8,641,774 B2
• Filed: 09/12/2008
• Issued: 02/04/2014
• Est. Priority Date: 09/14/2007
• Status: Active Grant

• Current Assignee: Curators of the University of Missouri (University of Missouri)
• Original Assignee: Curators of the University of Missouri (University of Missouri)
• Inventors: Rahaman, Mohamed Naushad, Bal, Bhajanjit Singh
• Primary Examiner(s): ANDERSON, GREGORY A
• Application Number:
  US12/209,943
• Publication Number:
  US 20090076624A1
• Time in Patent Office: 1,971 Days
• Field of Search: 623/23.72, 623/23.75, 623/23.63, 424424-426
• US Class Current: 623/23.72
• CPC Class Codes: A61F 2/2846 Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects nets or sleeves applied to surface of endoprostheses A61F2/30907; bone plates A61B17/80; bone regeneration in dental surgery A61C8/0006
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2002/2839 Bone plugs or bone graft dowels
• CPC Class Codes: A61F 2002/30761 Support means for artificial cartilage, e.g. cartilage defect covering membranes
• CPC Class Codes: A61F 2002/30762 Means for culturing cartilage
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders

Abstract

An osteochondral composite including a hydrogel with implanted biological cells joined to a porous supportive base at a mechanically-interlocked interface is disclosed. A method of fabricating the osteochondral composite and a method of treating damaged or diseased articular cartilage by implanting an osteochondral composite are also disclosed.

Claims

1. An osteochondral composite, comprising:

a) a porous supportive base defining an upper surface and a lower surface; and

,

b) a scaffolding layer defining an upper surface and a lower surface, wherein the lower surface of the scaffolding layer is formed within a plurality of pores of the porous support base to mechanically interlock with the upper surface of the porous supportive base, and wherein the scaffolding layer includes a hydrogel having biological cells implanted therein.

2. The osteochondral composite of claim 1, wherein the porous supportive base is constructed of a biocompatible material selected from the group consisting of allograft bone, metal, ceramic, polymer, and combinations thereof.

3. The osteochondral composite of claim 2, wherein the metal is selected from the group consisting of tantalum, titanium, niobium, and combinations thereof.

4. The osteochondral composite of claim 2, wherein the ceramic is selected from the group consisting of crystalline ceramic, hydroxyapatite, tricalcium phosphate, bioactive glass, bioactive glass-ceramic, and combinations thereof.

5. The osteochondral composite of claim 2, wherein the polymeric material is selected from the group consisting of polycaprolactone, poly(lactic acid), poly(glycolic acid), copolymers of lactic acid and glycolic acid, poly(ethylene glycol), and combinations thereof.

6. The osteochondral composite of claim 1, wherein the hydrogel is selected from the group consisting of polyethylene glycol, polylactic acid, polyglycolic acid, copolymers of lactic and glycolic acid, collagen, hyaluronan, agarose, alginate, dextran, chitosan, heparin, chondroitan sulfate, and combinations thereof.

7. The osteochondral composite of claim 1, wherein the porous supportive base is a cylinder with a diameter ranging between about 1 mm to about 100 mm.

8. The osteochondral composite of claim 1, wherein the porous supportive base has a thickness ranging between about 1 mm to about 100 mm.

9. The osteochondral composite of claim 1, wherein the scaffolding layer protrudes from the upper surface of the porous supportive base with a thickness ranging between about 0.1 mm to about 5 mm.

10. The osteochondral composite of claim 1, wherein the mechanically interlocked material of the porous supportive base and scaffolding layer has a thickness ranging between about 0.1 mm to about 5 mm.

11. The osteochondral composite of claim 1, wherein the mechanically interlocked material of the porous supportive base and scaffolding layer has a thickness ranging between about 1 mm to about 2 mm.

12. The osteochondral composite of claim 1, wherein the biological cells are selected from the group consisting of chondrocytes, chondroprogenitor cells, mesenchymal stem cells, mesenchymal progenitor cells, and combinations thereof.

13. An osteochondral composite, having three mechanically interlocked layers, the layers comprising:

a) a porous base layer defining an upper surface and a lower surface;

b) a transitional layer defining an upper surface and a lower surface, wherein the lower surface of the transitional layer is formed within a first plurality of pores of the porous base layer to mechanically interlock with the upper surface of the porous base layer; and

,

c) a scaffolding layer defining an upper surface and a lower surface wherein the lower surface of the scaffolding layer is formed within a first plurality of pores of the porous base layer to mechanically interlock with the upper surface of the transitional layer, wherein the scaffolding layer further includes a hydrogel with implanted biologic cells.

14. The osteochondral composite of claim 13, wherein the porous base layer comprises a biocompatible material selected from the group consisting of allograft bone, metal, ceramic, polymeric material, and combinations thereof.

15. The osteochondral composite of claim 14, wherein the metal is selected from the group consisting of tantalum, titanium, niobium, and combinations thereof.

16. The osteochondral composite of claim 14, wherein the polymeric material is selected from the group consisting of polycaprolactone, poly(lactic acid), poly(glycolic acid), copolymers of lactic acid and glycolic acid, poly(ethylene glycol), and combinations thereof.

17. The osteochondral composite of claim 14, wherein the ceramic is selected from the group consisting of crystalline ceramic, hydroxyapatite, tricalcium phosphate, bioactive glass, bioactive glass-ceramic, and combinations thereof.

18. The osteochondral composite of claim 13, wherein the hydrogel is selected from the group consisting of polyethylene glycol, polylactic acid, polyglycolic acid, copolymers of lactic and glycolic acid, collagen, hyaluronan, agarose, alginate, dextran, chitosan, heparin, chondroitan sulfate, and combinations thereof.

19. The osteochondral composite of claim 13, wherein the porous base layer is a cylinder with a diameter ranging between about 1 mm to about 100 mm.

20. The osteochondral composite of claim 13, wherein the thickness of the porous base layer ranges between about 1 mm to about 100 mm.

21. The osteochondral composite of claim 13, wherein the thickness of the scaffolding layer ranges between about 0.1 mm to about 5 mm.

22. The osteochondral composite of claim 13, wherein the transitional layer has a thickness ranging between about 0.1 mm to about 5 mm.

23. The osteochondral composite of claim 13, wherein the biological cells are selected from the group consisting of chondrocytes, chondroprogenitor cells, mesenchymal stem cells, mesenchymal progenitor cells, and combinations thereof.

24. A method of fabricating an osteochondral composite comprising:

a) providing a suspension comprising polymer and biological cells;

b) providing a porous base defining a plurality of pores, an upper surface and a lower surface;

c) submerging the upper surface of the porous base in the suspension to a predetermined depth; and

d) crosslinking the polymer within the plurality of pores such that a hydrogel is formed and is mechanically interlocked with the porous base.

25. The method of claim 24, wherein the method further comprises an additional step after step b) of partially crosslinking the polymer and an additional step after step c) of providing additional aqueous suspension of polymer and biological cells.

26. The method of claim 24, wherein the polymer comprises polyethylene glycol, polylactic acid, polyglycolic acid, copolymers of lactic and glycolic acid, collagen, hyaluronan, agarose, alginate, dextran, chitosan, heparin, chondroitan sulfate, and combinations thereof.

27. The method of claim 26, wherein the polymer further comprises photocrosslinkable moieties selected from the group consisting of methacrylate, methacrylate anhydride, acrylamide, propylene fumarate, and combinations thereof.

28. The method of claim 27, wherein the suspension comprises polyethylene diacrylate at a concentration ranging between about 5% to about 20% by weight.

29. The method of claim 24, wherein the suspension comprises a biocompatible photoinitiator.

30. The method of claim 29, wherein the biocompatible photoinitiator is selected from the group consisting of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone, and combinations thereof.

31. The method of claim 29, wherein the suspension comprises 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone at a concentration ranging between about 0.05% to about 0.2% by weight.

32. The method of claim 24, wherein the biological cells are selected from the group consisting of chondrocytes, chondroprogenitor cells, mesenchymal stem cells, mesenchymal progenitor cells, and combinations thereof.

33. The method of claim 24, wherein the porous base comprises a biocompatible material selected from the group consisting of allograft bone, metal, ceramic, polymer, and combinations thereof.

34. The method of claim 33, wherein the metal is selected from the group consisting of tantalum, titanium, niobium, and combinations thereof.

35. The method of claim 33, wherein the ceramic is selected from the group consisting of crystalline ceramic, hydroxyapatite, tricalcium phosphate, bioactive glass, bioactive glass-ceramic, and combinations thereof.

36. The method of claim 33, wherein the polymeric material is selected from the group consisting of polycaprolactone, poly(lactic acid), poly(glycolic acid), copolymers of lactic acid and glycolic acid, poly(ethylene glycol), and combinations thereof.

37. The method of claim 24, wherein the predetermined depth ranges between about 0.5 mm to about 5 mm.

38. The method of claim 24, wherein the crosslinking of the polymer is achieved using crosslinking methods selected from the group consisting of exposing the suspension to UV light, heating the suspension, contacting the suspension with a crosslinking catalyst compound, and combinations thereof.

39. A method of treating diseased or damaged articular cartilage in a vertebrate animal, comprising:

a) providing an osteochondral composite comprising a porous base defining a plurality of pores mechanically interlocked to a hydrogel with implanted biological cells, wherein at least a portion of the hydrogel is formed within the plurality of pores; and

,

b) implanting the osteochondral composite into a joint of the vertebrate animal.

40. The method of claim 39, wherein the joint is selected from the group consisting of hip, knee, shoulder, elbow, wrist, ankle, and interphalangial joints.

41. The method of claim 39, wherein the vertebrate animal is a human.