Open Access Open Badges Research article

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

Charles-Hubert Lafantaisie-Favreau1, Jessica Guzmán-Morales2, Jun Sun34, Gaoping Chen2, Adam Harris2, Thomas D Smith2, Alberto Carli5, Janet Henderson5, William D Stanish6 and Caroline D Hoemann12*

Author Affiliations

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

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BMC Musculoskeletal Disorders 2013, 14:27  doi:10.1186/1471-2474-14-27

Published: 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.

Cartilage repair; Bone marrow; Chitosan; Osteoclast; Neutrophil; Collagen; Marrow stimulation; Bone remodeling; Mesenchymal stromal cell; Micro-computed tomography