Composition and method for the repair and regeneration of cartilage and other tissues
The present invention relates to a new method for repairing human or animal tissues such as cartilage, meniscus, ligament, tendon, bone, skin, cornea, periodontal tissues, abscesses, resected tumors, and ulcers. The method comprises the step of introducing into the tissue a temperature-dependent polymer gel composition such that the composition adhere to the tissue and promote support for cell proliferation for repairing the tissue. Other than a polymer, the composition preferably comprises a blood component such as whole blood, processed blood, venous blood, arterial blood, blood from bone, blood from bone-marrow, bone marrow, umbilical cord blood, placenta blood, erythrocytes, leukocytes, monocytes, platelets, fibrinogen, thrombin and platelet rich plasma. The present invention also relates to a new composition to be used with the method of the present invention.
1. A method for repair and/or regeneration in cartilaginous tissue comprising administering at a site of the cartilaginous tissue in need of repair an effective amount of a polymer composition comprising:
a solution of a polymer; and
blood,
wherein the polymer includes at least one selected from the group consisting of a polysaccharide, a protein, and a polyamino acid, and further wherein when the polymer is combined with blood the polymer composition is converted into a non-liquid state in time or upon heating such that the polymer compositions when placed at the site in need of repair, the polymer composition will adhere to the site in need of repair to effect reconstruction or bulking of the tissue and/or regeneration thereof.
2. The method of claim 1 , wherein the polysaccharide is a modified or natural polysaccharide.
3. The method of claim 2 , wherein the polysaccharide is selected from the group consisting of chitosan, chitin, hyaluronan, glycosaminoglycan, chondroitin sulfate, keratan sulfate, dermatan sulfate, heparin, and heparin sulfate.
4. The method of claim 1 , wherein the polysaccharide is chitosan.
5. The method of claim 1 , wherein cartilaginous tissue is selected from the group consisting of cartilage, meniscus, ligament and tendon.
6. The method of claim 1 , wherein the protein is a natural, recombinant or synthetic protein.
7. The method of claim 3 , wherein said protein is a polyamino acid.
8. The method of claim 7 , wherein the polyamino acid is a polylysine.
9. The method of claim 6 , wherein the natural protein is soluble collagen or gelatin.
10. The method of claim 1 , wherein the polymer composition is dissolved or suspended in a buffer containing organic or inorganic salts.
11. The method of claim 10 , wherein the inorganic salts are selected from the group consisting of sodium chloride or phosphates, sulfates or carboxylates of potassium, calcium and magnesium.
12. The method of claim 1 , wherein said polymer composition has a pH between 6.5 and 7.8.
13. The method of claim 1 , wherein said polymer solution has an osmolarity adjusted to a physiological value between 250 mOsm/L and 600 mOsm/L.
14. The method of claim 1 , wherein the blood is anticoagulated.
15. The method of claim 1 , wherein the blood further comprises an anticoagulant selected from the group consisting of citrate, heparin or EDTA.
16. The method of claim 1 , wherein the blood further comprises a pro-coagulant to improve coagulation/solidification at the site of introduction.
17. The method of claim 1 , wherein the pro-coagulant is selected from the group consisting of thrombin, calcium, collagen, ellagic acid, epinephrine, adenosine diphosphate, tissue factor, a phospholipid, and a coagulation factor.
18. The method of claim 1 , wherein the blood is autologous or non-autologous.
19. The method of claim 18 , wherein the blood is free of at least one of erythrocytes and/or leukocytes.
20. The method of claim 18 , wherein the blood is enriched in platelets.
21. The method of claim 1 , wherein the polymer composition is used in a ratio varying from 1:100 to 100:1 with respect to the blood.
22. The method of claim 1 , wherein said polymer and blood are mechanically mixed using sound waves, stirring, vortexing, or multiple passes in syringes.
23. The method of claim 10 , wherein the organic salts are selected from the group consisting of glycerol-phosphate, fructose phosphate, glucose phosphate, L-serine phosphate, adenosine phosphate, glucosamine, galactosamine, HEPES, PIPES and MES.
24. The method of claim 1 , wherein the blood is selected from the group consisting of whole blood, processed blood, venous blood, arterial blood, blood from bone-marrow, umbilical cord blood and placenta blood.
25. The method of claim 17 , wherein the coagulation factor is factor VII.
26. The method of claim 4 , wherein the chitosan is dissolved in an organic or inorganic phosphate buffer.
27. The method of claim 26 , wherein the organic or inorganic phosphate buffer is a phosphate or glycerol phosphate containing buffer.
28. The method of claim 26 , wherein the chitosan in the composition is in a soluble state, said composition having a pH between 6.5 and 7.4.
29. The method of claim 1 , wherein the cartilaginous tissue is selected from the group consisting of articular cartilage, nose cartilage, ear cartilage, meniscus and avascular cartilage.
30. A method for repair and/or regeneration in cartilaginous tissue comprising administering at a site of the cartilaginous tissue in need of repair an effective amount of a thermogelling composition comprising:
a solution of the polymer chitosan;
glycerol phosphate; and
blood,
wherein the thermogelling composition is converted into a non-liquid state in time or upon heating, said composition once converted into a non-liquid state adheres to the site in need of repair when placed thereon to effect reconstruction or bulking of the tissue and/or regeneration thereof.
31. The method of claim 30 , wherein cartilaginous tissue is selected from the group consisting of cartilage, meniscus, ligament and tendon.
32. The method of claim 30 , wherein said polymer composition has a pH between 6.5 and 7.8, and wherein said chitosan is in solution at said pH.
33. The method of claim 30 , wherein said polymer solution has an osmolarity adjusted to a physiological value between 250 mOsm/L and 600 mOsm/L.
34. The method of claim 30 , wherein the blood is anticoagulated.
35. The method of claim 30 , wherein the blood further comprises an anticoagulant selected from the group consisting of citrate, heparin or EDTA.
36. The method of claim 30 , wherein the blood further comprises a pro-coagulant to improve coagulation/solidification at the site of introduction.
37. The method of claim 30 , wherein the pro-coagulant is selected from the group consisting of thrombin, calcium, collagen, ellagic acid, epinephrine, adenosine diphosphate, tissue factor, a phospholipid, and a coagulation factor.
38. The method of claim 30 , wherein the blood is autologous or non-autologous.
39. The method of claim 38 , wherein the blood is free of at least one of erythrocytes and/or leukocytes.
40. The method of claim 38 , wherein the blood is enriched in platelets.
41. The method of claim 30 , wherein said chitosan, glycerol phosphate and blood are mechanically mixed using sound waves, stirring, vortexing, or multiple passes in syringes.
42. The method of claim 30 , wherein the blood is selected from the group consisting of whole blood, processed blood, venous blood, arterial blood, blood from bone-marrow, umbilical cord blood and placenta blood.
43. The method of claim 37 , wherein the coagulation factor is factor VII.
44. The method of claim 30 , wherein the cartilaginous tissue is selected from the group consisting of articular cartilage, nose cartilage, ear cartilage, meniscus and avascular cartilage.