Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition
1 Institute of Biomedical Engineering, École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, H3C 3A7, Canada
2 Department of Chemical Engineering, École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, H3C 3A7, Canada
3 Biosyntech/Piramal HealthCare Canada Inc, 475 Armand Frappier, Laval, QC, H7V 4B3, Canada
4 Current address: Comparative Orthopaedic Research Lab, Department of Clinical Studies, University of Guelph, 50 McGilvray, Lane Guelph, ON, N1G 2W1, Canada
5 The Research Institute of the McGill University Health Centre, Montreal General Hospital, 1650 Cedar Ave, Montréal, QC, H3G 1A4, Canada
6 Orthopaedic and Sport Medicine Clinic of Nova Scotia, Dalhousie University, 5595 Fenwick St., Suite 311, Halifax, NS, B3H 4M2, Canada
BMC Musculoskeletal Disorders 2013, 14:27 doi:10.1186/1471-2474-14-27Published: 16 January 2013
In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls.
Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair.
All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue.
Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair.