Device for regeneration of articular cartilage and other tissue

• US 7,776,100 B2
• Filed: 09/08/2004
• Issued: 08/17/2010
• Est. Priority Date: 05/13/1994
• Status: Expired due to Fees

• Current Assignee: Kensey Nash Corporation (DSM-Firmenich AG)
• Original Assignee: Kensey Nash Corporation (DSM-Firmenich AG)
• Inventors: Goldman, Scott M., Bradica, Gino, Brekke, John H.
• Primary Examiner(s): Philogene; Pedro
• Application Number:
  US10/936,020
• Publication Number:
  US 20050074481A1
• Time in Patent Office: 2,169 Days
• Field of Search: 623/23.27, 623/23.72, 623/23.76, 623/23.56, 623/16.11, 623/1.42, 424/426, 424/501, 424/93.7, 424/486, 424/468, 424/488, 424/93.1
• US Class Current: 623/23.72
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/15 Depsipeptides; Derivatives thereof
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body

Abstract

An implantable device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment includes a cartilage region comprising a polyelectrolytic complex joined with a subchondral bone region. The cartilage region, of this embodiment, enhances the environment for chondrocytes to grow articular cartilage; while the subchondral bone region enhances the environment for cells which migrate into that region'"'"'s macrostructure and which differentiate into osteoblasts. A hydrophobic barrier exists between the regions, of this embodiment. In one embodiment, the polyelectrolytic complex transforms to hydrogel, following the implant procedure.

Claims

1. A device for facilitating healing of voids in tissue comprising,

(a) in its dry state, a macrostructure defining void spaces, the macrostructure comprising a regeneration complex comprising a polyelectrolytic complex and at least one additive mixed or blended into, but not bound to, said polyelectrolytic complex, said additive comprising at least one member selected from the group consisting of a protein, a polysaccharide, a lipid, a synthetic polymer, and a ceramic, said regeneration complex possessing sufficient structural integrity as to permit handling, the device being suitable and arranged for implantation into said void of said tissue of a living being;

and

(b) wherein in a hydrated state, at least one region of said device swells.

2. The device of claim 1, with the device being bioresorbable.

3. The device of claim 1, with the macrostructure further comprising a material chosen from the group consisting of:

aliphatic polyesters, polyanhydrides, polyorthoesters, polysaccharides, and polycaprolactone.

4. The device of claim 1 further comprising at least a first region and a second region.

5. The device of claim 4 further comprising a barrier for inhibiting water-based fluid.

6. The device of claim 5 with the barrier comprising a first interface and a second interface and arranged between the first region and the second region.

7. The device of claim 5 with the barrier being hydrophobic.

8. The device of claim 5, with the barrier allowing cell migration.

9. The device of claim 4, with at least one of the regions being hydrophilic, and at least one of the regions being hydrophobic, with the hydrophilic region rendered hydrophilic by use of a treatment selected from the group consisting of:

surfactant, ion-beam activation process, plasma treatment, radio frequency application, ultrasound treatment, radiation, or thermal treatment.

10. The device of claim 4, further comprising at least one additional region to bridge the first region and the second region, the additional region comprising a macrostructure, delineating voids.

11. The device of claim 1, with the polyelectrolytic complex comprising a polyanion and a polycation.

12. The device of claim 11, with the polycation comprising chitosan.

13. The device of claim 11, with the polycation comprising collagen.

14. The device of claim 13, with the collagen comprising demineralized bone matrix.

15. The device of claim 14, with the demineralized bone matrix comprising secondary constituents.

16. The device of claim 11, with the polyanion comprising at least one glycosaminoglycan.

17. The device of claim 16, with the at least one glycosaminoglycan being selected from the group consisting of:

hyaluronic acid, heparin, chondroitin-4-SO₄, chondroitin-6-SO₄, keratin sulfate, or dermatan-SO₄.

18. The device of claim 1, with the polyelectrolytic complex transforming to hydrogel following hydration.

19. The device of claim 18, with the hydration following device implantation.

20. The device of claim 18, with the hydration preceding device implantation.

21. The device of claim 18, with the transformation to hydrogel causing the hydrogel to impede trans-implant communication of biologically active agents while allowing mass transfer, cell respiration and biological functions to continue.

22. The device of claim 9, with the hydrophilic region attracting and causing infiltration of the hydrophilic region with water-based fluids.

23. The device of claim 1, further comprising a therapy.

24. The device of claim 23, with the therapy comprising a biologically active agent.

25. The device of claim 1, wherein said device is capable of imbibing at least one water-based fluid to create a wet or hydrated state.

26. The device of claim 25, wherein said polyelectrolytic complex comprises fibers.

27. The device of claim 26, wherein in a prolonged hydrated state, some water-based fluid is bound to said fibers to form hydrated filaments, and additional water-based fluid becomes entrapped between said hydrated filaments, thereby forming a hydrogel.

28. The device of claim 23, wherein said therapy is located within the macrostructure.

29. The device of claim 23, wherein said therapy is located within the voids spaces defined by the macrostructure.

30. The device of claim 1, wherein said macrostructure is processed by at least one technique selected from the group consisting of injection molding, vacuum forming, spinning hollow filaments, solvent evaporation and soluble particulate leaching.

32. The device of claim 1, wherein said polyelectrolytic complex comprises hyaluronic acid and chitosan, and further wherein said additive comprises at least one of hyaluronic acid and chitosan.

33. The device of claim 1, wherein said protein comprises at least one member selected from the group consisting of collagen, carrageenan, fibrin, elastin, resilin, abductin, demineralized bone, and agarose.

34. The device of claim 1, wherein said polysaccharaide comprises at least one member selected from the group consisting of cellulose, starches, chitosan, alginate, and glycosaminoglycans.

35. The device of claim 34, wherein said glycosaminoglycans is hyaluronic acid.

36. The device of claim 1, wherein said lipid comprises at least one member selected from the group consisting of phospholipids, triglyceride, waxes, steroids, prostaglandins, and terpenes.

37. The device of claim 1, wherein said synthetic polymer comprises at least one member selected from the group consisting of polylactide, polyglycolide, polyurethane, poly-ε

-caprolactone, polyvinyl alcohol, polycarbonate and PTFE.

39. The device of claim 1, wherein said swelling aids in securing said device in said living being following implantation.

31. A device for facilitating healing of voids in tissue comprising, in its dry state, a polyelectrolytic complex in the form of a three-dimensional architecture defining void spaces, said polyelectrolytic complex possessing sufficient strength as to permit handling, said device furthermore comprising at least one additive unbound to said polyelectrolytic complex, said at least one additive selected from the group consisting of a protein, a polysaccharide, a lipid, a synthetic polymer, and a ceramic, wherein in its hydrated state, at least one region of said device is swollen.

40. The device of claim 31, wherein said swollen condition aids in securing said device following implantation into said void in said tissue.

38. A device for facilitating healing of voids in tissue comprising,

(a) in its dry state, a macrostructure defining void spaces, the macrostructure comprising a regeneration complex comprising a polyelectrolytic complex and at least one additive mixed or blended into, but not bound to, said polyelectrolytic complex, said additive comprising at least one member selected from the group consisting of a lipid and a ceramic, said regeneration complex polyelectrolytic complex fibers formed from chitosan and hyaluronic acid, regions of chitosan not bound to said polyelectrolytic complex fibers, and regions of hyaluranic acid not bound to said polyelectrolytic complex fibers,

(b) wherein upon hydration the regeneration complex forms a three dimensional network of polyeletrolytic complex filaments and chitosan and hyaluronic acid viscoelastic gel,

(c) the device being suitable and arranged for implantation into said void of said tissue of a living being.