title: Acute Osteoclast Activity following Subchondral Drilling Is Promoted by Chitosan and Associated with Improved Cartilage Repair Tissue Integration.
abstract: OBJECTIVE
  Cartilage-bone integration is an important functional end point of cartilage repair therapy, but little is known about how to promote integration. We tested the hypothesis that chitosan-stabilized blood clot implant elicits osteoclasts to drilled cartilage defects and promotes repair and cartilage-bone integration.
  
  
  METHODS
  Bilateral trochlear defects in 15 skeletally mature rabbit knees were microdrilled and then treated with chitosan-glycerol phosphate (GP)/blood implant with fluorescent chitosan tracer and thrombin to accelerate in situ solidification or with thrombin alone. Chitosan clearance, osteoclast density, and osteochondral repair were evaluated at 1, 2, and 8 weeks at the outside, edge, and through the proximal microdrill holes.
  
  
  RESULTS
  Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks. Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks. Implants elicited 2-fold more osteoclasts relative to controls (P < 0.001), a more complete drill hole bone repair, and improved cartilage-bone integration and histological tissue quality. Treated and control 8-week cartilage repair tissues contained 85% collagen type II. After 8 weeks of repair, subchondral osteoclast density correlated positively with bone-cartilage repair tissue integration (P < 0.0005).
  
  
  CONCLUSIONS
  Chitosan-GP/blood implant amplified the acute influx of subchondral osteoclasts through indirect mechanisms, leading to significantly improved repair and cartilage-bone integration without inducing net bone resorption. Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.
authors.affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: BioSyntech Canada Inc., Laval, Quebec, Canada ; Piramal Healthcare (Canada), Laval, Quebec, Canada Institution where the work reported was done: Ecole Polytechnique, Montreal, Quebec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Lascau-Coman
authors.affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Chevrier
authors.affiliation: Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Marchand
authors.affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada ; Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.
authors.forename: Caroline D
authors.initials: CD
authors.lastname: Hoemann
keywords: animal model; chitosan; marrow stimulation; osteochondral repair; osteoclast