Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects.
BACKGROUND
Microfracture is a surgical procedure that is used to treat focal articular cartilage defects. Although joint function improves following microfracture, the procedure elicits incomplete repair. As blood clot formation in the microfracture defect is an essential initiating event in microfracture therapy, we hypothesized that the repair would be improved if the microfracture defect were filled with a blood clot that was stabilized by the incorporation of a thrombogenic and adhesive polymer, specifically, chitosan. The objectives of the present study were to evaluate (1) blood clot adhesion in fresh microfracture defects and (2) the quality of the repair, at six months postoperatively, of microfracture defects that had been treated with or without chitosan-glycerol phosphate/blood clot implants, using a sheep model.


METHODS
In eighteen sheep, two 1-cm2 full-thickness chondral defects were created in the distal part of the femur and treated with microfracture; one defect was made in the medial femoral condyle, and the other defect was made in the trochlea. In four sheep, microfracture defects were created bilaterally; the microfracture defects in one knee received no further treatment, and the microfracture defects in the contralateral knee were filled with chitosan-glycerol phosphate/autologous whole blood and the implants were allowed to solidify. Fresh defects in these four sheep were collected at one hour postoperatively to compare the retention of the chitosan-glycerol phosphate/blood clot with that of the normal clot and to define the histologic characteristics of these fresh defects. In the other fourteen sheep, microfracture defects were made in only one knee and either were left untreated (control group; six sheep) or were treated with chitosan-glycerol phosphate/blood implant (treatment group; eight sheep), and the quality of repair was assessed histologically, histomorphometrically, and biochemically at six months postoperatively.


RESULTS
In the defects that were examined one hour postoperatively, chitosan-glycerol phosphate/blood clots showed increased adhesion to the walls of the defects as compared with the blood clots in the untreated microfracture defects. After histological processing, all blood clots in the control microfracture defects had been lost, whereas chitosanglycerol phosphate/blood clot adhered to and was partly retained on the surfaces of the defect. At six months, defects that had been treated with chitosan-glycerol phosphate/blood were filled with significantly more hyaline repair tissue (p < 0.05) compared with control defects. Repair tissue from medial femoral condyle defects that had been treated with chitosan-glycerol phosphate/blood contained more cells and more collagen compared with control defects and showed complete restoration of glycosaminoglycan levels.


CONCLUSIONS
Solidification of a chitosan-glycerol phosphate/blood implant in microfracture defects improved cartilage repair compared with microfracture alone by increasing the amount of tissue and improving its biochemical composition and cellular organization.
Hoemann
Caroline D
CD
Department of Chemical Engineering and Institute of Biomedical Engineering, Ecole Polytechnique, P.O. Box 6079, Station Centre-Ville, Montréal, Quebec H3C 3A7, Canada. caroline.hoemann@polymtl.ca.
Hurtig
Mark
M
Comparative Orthopaedic Research Laboratory, Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Rossomacha
Evgeny
E
BioSyntech Inc., 475 Armand-Frappier Boulevard, Laval, Quebec H7V 4B3, Canada.
Sun
Jun
J
BioSyntech Inc., 475 Armand-Frappier Boulevard, Laval, Quebec H7V 4B3, Canada.
Chevrier
Anik
A
Department of Chemical Engineering and Institute of Biomedical Engineering, Ecole Polytechnique, P.O. Box 6079, Station Centre-Ville, Montréal, Quebec H3C 3A7, Canada. caroline.hoemann@polymtl.ca.
Shive
Matthew S
MS
BioSyntech Inc., 475 Armand-Frappier Boulevard, Laval, Quebec H7V 4B3, Canada.
Buschmann
Michael D
MD
Department of Chemical Engineering and Institute of Biomedical Engineering, Ecole Polytechnique, P.O. Box 6079, Station Centre-Ville, Montréal, Quebec H3C 3A7, Canada. caroline.hoemann@polymtl.ca.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002357:Cartilage Diseases / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D048271:Chitosan / Q000494:pharmacology* / Q000627:therapeutic use; D003029:Coagulants / Q000494:pharmacology* / Q000627:therapeutic use; D005990:Glycerol / Q000494:pharmacology / Q000627:therapeutic use; D006818:Hyalin / Q000187:drug effects; D023421:Models, Animal; D019637:Orthopedic Procedures / Q000379:methods*; D010710:Phosphates / Q000494:pharmacology / Q000627:therapeutic use; D019736:Prostheses and Implants; D012756:Sheep; D014945:Wound Healing / Q000187:drug effects*
D003029:Coagulants; D010710:Phosphates; D048271:Chitosan; D005990:Glycerol