Cartilage implant plug with fibrin glue and method for implantation

• US 20050064042A1
• Filed: 10/12/2004
• Published: 03/24/2005
• Est. Priority Date: 04/29/2003
• Status: Abandoned Application

• Current Assignee: Massachusetts Institute of Technology, Musculoskeletal Transplant Foundation
• Original Assignee: Musculoskeletal Transplant Foundation
• Inventors: Sunwoo, Moon Hae, Gertzman, Arthur A., Vunjak-Novakovic, Gordana, Truncale, Katherine Ann Gomes
• Application Number:
  US10/960,960
• Publication Number:
  US 20050064042A1
• Time in Patent Office: Days
• US Class Current: 424/549
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• 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 2/3859 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 2002/2839 Bone plugs or bone graft dowels
• 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 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 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/363 Fibrinogen
• CPC Class Codes: A61K 38/4833 Thrombin (3.4.21.5)
• CPC Class Codes: A61L 2300/414 : Growth factors
• CPC Class Codes: A61L 2300/43 : Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/64 : Animal cells
• CPC Class Codes: A61L 24/0005 : Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 24/0015 : Medicaments; Biocides
• CPC Class Codes: A61L 2430/06 : for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/3608 : Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/3612 : Cartilage, synovial fluid
• CPC Class Codes: A61L 27/3654 : Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3687 : characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/38 : containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3817 : Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/48 : with macromolecular fillers
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders

Abstract

The invention is directed toward a cartilage repair assembly comprising a shaped structure of subchondral bone with an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans and milled cartilage in a bioabsorbable carrier. The shaped structure is dimensioned to fit in a drilled bore in a cartilage defect area so that said shaped bone and cartilage cap when centered in the bore does not engage the side wall of the bore and is positioned from the side wall of the bone a distance ranging from 10 microns to 1000 microns and is surrounded by milled cartilage and a fibrin thrombin glue. A method for inserting the assembly into a cartilage defect area is disclosed.

Claims

1. A cartilage repair assembly comprising a sterile shaped structure of subchondral bone and overlying integral cartilage cap, said shaped structure been dimensioned to fit in a drilled bore in a cartilage defect are so that said shaped bone and hyaline cartilage cap when centered in the bore can be rotated in said bore, the shaped structure when placed in the bore forming a gap ranging from 10 microns to 2 mm, said bone plug being treated to remove cellular debris and proteoglycans and sterile milled allograft cartilage pieces mixed in a thrombin fibrinogen solution surrounding at least a portion of a side wall of shaped structure in said bore.

2. A cartilage repair assembly as claimed in claim 1 wherein said milled cartilage pieces are sized less than 1 mm.

3. A cartilage repair assembly as claimed in claim 1 wherein said cartilage is hyaline allograft cartilage.

4. A cartilage repair assembly as claimed in claim 1 wherein said milled cartilage is fibrocartilage.

5. A cartilage repair assembly as claimed in claim 1 wherein said milled cartilage is a mixture of fibrocartilage and hyaline cartilage.

6. A cartilage repair assembly as claimed in claim 1 wherein said cartilage thrombin fibrinogen solution mixture includes demineralized bone powder having a size ranging from 200 to 850 microns with a weight ranging from 1% to 35% of the cartilage thrombin fibrogen solution mixture.

7. A cartilage repair assembly as claimed in claim 1 wherein said mixed allograft milled cartilage pieces includes adding allograft chondrocyte cells in amount ranging from 10×

10⁶ to 10×

10⁷.

8. A method of placing a preshaped allograft implant assembly in a cartilage defect, said assembly comprising a subchondral bone and an overlying cartilage cap plug which has been treated to remove cellular debris and proteoglycans and minced cartilage in a carrier comprising the steps of:

(a) drilling a cylindrical hole in a patient at a site of a cartilage defect to a depth which equal to or less than the length of the bone and cartilage cap plug implant to be placed therein forming a blind bore;

(b) placing a preshaped osteochondral plug having a cross section which is less than the cross sectional area of the bore with a gap between the exterior surface of the plug and at least one side wall defining the drilled bore being less than 2 mm allowing the implant to be laterally moveable within-said bore in the cylindrical hole;

(c) mixing minced allograft cartilage in a fibrinogen thrombin solution; and

(d) placing the minced cartilage in fibrinogen thrombin solution in the gap between the plug and at least on side wall defining the bore and allowing the cartilage and solution to polymerize.

9. A method as claimed in claim 8 including an additional step of adding a thrombin solution over the polymerized mixture.

10. A method as claimed in claim 8 including an additional step of adding a fibrinogen solution over the polymerized mixture

11. A method as claimed in claim 8 wherein said gap ranges from between 10 microns and 1000 microns.

12. A method as claimed in claim 8 wherein said minced cartilage ranges from about 0.01 mm to about 0.12 mm in size.

13. A method as claimed in claim 8 wherein said assembly includes adding chondrocyte cells from one or more of a group consisting of allograft and autograft.

14. A method as claimed in claim 13 wherein said chondrocyte cells are added in amount ranging from 10.0×

10⁶ to 10.0×

10⁷.

15. A method as claimed in claim 13 wherein said chondrocyte cells are added in amount ranging from 2.0×

10⁷ to 4.0×

10⁷.

16. A method as claimed in claim 8 wherein said assembly includes adding a chondrogenic factor taken from a group consisting of growth factors (FGF-2, FGF-5, FGF-9, IGF-1, TGF-β

, BMP-2, BMP-7, PDGF, VEGF), human allogenic or autologous chondrocytes, human allogenic cells, human allogenic or autologous bone marrow cells, human autologous and allogenic human stem cells, demineralized bone matrix, insulin, insulin-like growth factor-1, interleukin-1 receptor antagonist, hepatocyte growth factor, platelet-derived growth factor, Indian hedgehog and parathyroid hormone-related peptide.

17. A method of placing a preshaped allograft implant assembly in a cartilage defect, said assembly comprising a subchondral bone and an overlying cartilage cap plug which has been treated to remove cellular debris and proteoglycans and minced cartilage in a carrier comprising the steps of:

(a) drilling a hole in a patient at a site of a cartilage defect to a depth which equal to or less than the length of a bone and cartilage cap plug implant to be placed therein forming a blind bore;

(b) placing a preshaped osteochondral plug having a cross section which is less than the cross sectional area of the bore with a gap ranging from between 10 microns and 1000 microns in size between the exterior surface of the plug and one or more side walls defining the drilled bore being less than 2 mm allowing the implant to be laterally moveable within said bore in the cylindrical hole;

(c) mixing minced allograft cartilage in a fibrinogen thrombin solution; and

(d) placing the minced cartilage in fibrinogen thrombin solution in the gap between the plug and the one or more side walls defining the blind bore and allowing the cartilage and solution to polymerize.

18. A method as claimed in claim 17 wherein said minced cartilage ranges from about 0.01 mm to about 0.12 mm in size.

19. A method as claimed in claim 17 including a separate step of adding a fibrinogen solution over the polymerized solution.

20. A method as claimed in claim 17 wherein said fibrinogen thrombin mixture is of equal quantity.

21. A method as claimed in claim 17 including the step of adding chondrocyte cells from one or more of a group consisting of allograft and autograft chondrocyte cells to said plug.

22. A method as claimed in claim 21 wherein said chondrocyte cells are added in amount ranging from 2.0×

10⁷ to 4.0×

10⁷.

23. A method as claimed in claim 21 wherein said chondrocyte cells are added in amount ranging from 10.0×

10⁶ to 10.0×

10⁷.

24. A method as claimed in claim 17 including the step of adding chondrocyte cells from one or more of a group consisting of allograft and autograft chondrocyte cells to said fibrinogen thrombin solution.

25. A method as claimed in claim 24 wherein said chondrocyte cells are added in amount ranging from 2.0×

10⁷ to 4.0×

10⁷.

26. A method as claimed in claim 24 wherein said chondrocyte cells are added in amount ranging from 10.0×

10⁶ to 10.0×

10⁷.

27. A method as claimed in claim 17 where said mixed solution is allowed to polymerize for about 3 minutes.

28. A method as claimed in claim 17 including an additional step of adding a thrombin solution over the polymerized mixture.

29. A method as claimed in claim 17 including an additional step of adding a fibrinogen solution over the polymerized mixture.

30. A method as claimed in claim 17 wherein said assembly includes adding a chondrogenic factor taken from a group consisting of growth factors (FGF-2, FGF-5, FGF-9, IGF-1, TGF-β

, BMP-2, BMP-7, PDGF, VEGF), human allogenic or autologous chondrocytes, human allogenic cells, human allogenic or autologous bone marrow cells, human autologous and allogenic human stem cells, demineralized bone matrix, insulin, insulin-like growth factor-1, interleukin-1 receptor antagonist, hepatocyte growth factor, platelet-derived growth factor, Indian hedgehog and parathyroid hormone-related peptide.