CARTILAGE REPAIR MIXTURE CONTAINING ALLOGRAFT CHONDROCYTES

• US 20110196508A1
• Filed: 02/11/2011
• Published: 08/11/2011
• Est. Priority Date: 04/29/2003
• Status: Abandoned Application

• Current Assignee: Musculoskeletal Transplant Foundation
• Original Assignee: Musculoskeletal Transplant Foundation
• Inventors: Tomford, William W., Sunwoo, Moon Hae, Truncale, Katherine Gomes, Gertzman, Arthur A.
• Application Number:
  US13/025,722
• Publication Number:
  US 20110196508A1
• Time in Patent Office: Days
• US Class Current: 623/23.72
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30744 End caps, e.g. for closing an endoprosthetic cavity
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2/3859 Femoral components
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/2835 Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/30225 Flat cylinders, i.e. discs
• CPC Class Codes: A61F 2002/30759 Mosaicplasty, i.e. using a plurality of individual cartilage plugs for filling a substantial cartilage defect
• CPC Class Codes: A61F 2002/30764 Cartilage harvest sites
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61F 2310/00383 Gelatin
• 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 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/18 : Growth factors; Growth regulators
• CPC Class Codes: A61K 38/28 : Insulins
• CPC Class Codes: A61L 2430/06 : for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/20 : Polysaccharides
• CPC Class Codes: A61L 27/24 : Collagen
• CPC Class Codes: A61L 27/3612 : Cartilage, synovial fluid
• CPC Class Codes: A61L 27/3654 : Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3683 : subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/3817 : Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3821 : Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• 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 27/48 : with macromolecular fillers
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The invention is directed toward a sterile cartilage defect implant material comprising milled lyophilized allograft cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or mixed polymers with allograft chondrocytes added in an amount ranging from 2.5×10⁵ to 2.5×10⁷.

Claims

1-20. -20. (canceled)

21. A method of repairing an articular cartilage defect in a human being, comprising the step of placing in a cartilage defect site, allograft chondrocytes and lyophilized, freeze-milled allograft cartilage pieces, the allograft cartilage pieces having a size not greater than 1 mm.

22. A method as claimed in claim 21, wherein the allograft cartilage pieces are included in a mixture that also includes a bioabsorbable carrier selected from the group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran and polymers.

23. A method as claimed in claim 22, wherein the allograft cartilage pieces are present in the mixture in an amount within the range from about 15% to about 50% by weight, and the bioabsorbable carrier is present in the mixture in an amount within the range from about 50% to about 85% by weight.

24. A method as claimed in claim 21, wherein the allograft chondrocytes are derived from allograft cartilage taken from a human donor having an age in the range from about 3 months to about 20 years.

25. A method as claimed in claim 24, wherein the allograft cartilage pieces are formed from allograft cartilage taken from a human donor having an age in the range from about 3 months to about 20 years.

26. A method as claimed in claim 21, wherein the allograft chondrocytes are derived from allograft cartilage taken from a human donor having an age in the range from about 3 months to about 12 years.

27. A method as claimed in claim 21, wherein the allograft chondrocytes are derived from allograft cartilage taken from a human donor and the allograft cartilage pieces are formed from allograft cartilage taken from the same human donor.

28. A method as claimed in claim 21, wherein the allograft chondrocytes are placed in the cartilage defect site in an amount ranging from about 2.5×

10⁵ to about 2.5×

10⁷ allograft chondrocytes.

29. A method as claimed in claim 28, wherein the allograft chondrocytes are placed in the cartilage defect site in an amount of about 2.5×

10⁶ allograft chondrocytes.

30. A method as claimed in claim 28, wherein the allograft chondrocytes include expanded growth chondrocytes.

31. A method as claimed in claim 21, wherein the allograft cartilage pieces are formed from allograft articular cartilage.

32. A method as claimed in claim 21, wherein the allograft cartilage pieces are formed from allograft cartilage selected from the group consisting of hyaline cartilage and fibrous cartilage.

33. A method as claimed in claim 21, further comprising the step of placing a growth factor in the cartilage defect site.

34. A method as claimed in claim 21, wherein the allograft cartilage pieces have a water content ranging from about 0.1% to about 8.0% by weight prior to being placed in the cartilage defect site.

35. A method as claimed in claim 21, wherein the allograft cartilage pieces are formed from allograft cartilage which has been lyophilized so as to reduce its water content to an amount within the range from about 0.1% to about 8.0% by weight.

36. A method as claimed in claim 21, wherein the size is in the range from about 0.01 mm to 1.0 mm.

37. A method as claimed in claim 21, wherein the allograft cartilage pieces are formed from a donor tissue material consisting of allograft articular cartilage.

38. A method as claimed in claim 21, wherein the allograft cartilage pieces are formed by a method including the steps of:

(a) harvesting a donor tissue material consisting of allograft articular cartilage; and

(b) lyophilizing and freeze-milling the donor tissue material.

39. A method as claimed in claim 21, wherein the allograft cartilage pieces are formed by freezing allograft cartilage with liquid nitrogen and milling the frozen cartilage.

40. A method as claimed in claim 21, wherein the allograft cartilage pieces are formed by freeze-milling allograft cartilage that has been lyophilized.

41. A method as claimed in claim 21, wherein said placing step includes the steps of:

(a) cutting a patient'"'"'s tissue to remove a diseased area of cartilage from the cartilage defect site;

(b) placing the allograft chondrocytes and allograft cartilage pieces into the cartilage defect site; and

(c) placing a cover over the allograft chondrocytes and allograft cartilage pieces so as to contain the allograft chondrocytes and allograft cartilage pieces in the cartilage defect site.

42. A method as claimed in claim 21, further comprising the step of fixing the allograft cartilage pieces in the cartilage defect site with an organic glue.

43. A method as claimed in claim 41, further comprising the step of keeping the cover over the allograft chondrocytes and allograft cartilage pieces for a predetermined period of time that is sufficient to promote articular cartilage growth at the cartilage defect site.

44. A method as claimed in claim 41, wherein the cover includes one of a periosteal flap and a perichondrial flap.

45. A method as claimed in claim 22, wherein the mixture further includes the allograft chondrocytes.

46. A method as claimed in claim 21, wherein the allograft cartilage pieces lack viable cells.

47. A method as claimed in claim 21, wherein the allograft cartilage pieces have an ability to stimulate growth of new articular cartilage at the defect site.

48. A method as claimed in claim 22, wherein the mixture further includes a growth factor selected from the group consisting of FGF-2, FGF-5, IGF-1, TGF-β

, BMP-2, BMP-7, PDGF, and VEGF.

49. A method as claimed in claim 48, wherein said placing step includes (i) the step of placing said allograft chondrocytes in the cartilage defect site;

and (ii) placing the lyophilized, freezer-milled cartilage pieces in the cartilage defect site, said step (i) being performed separately from said step (ii).