title: Bone-Induced Chondroinduction in Sheep Jamshidi Biopsy Defects with and without Treatment by Subchondral Chitosan-Blood Implant: 1-Day, 3-Week, and 3-Month Repair.
abstract: OBJECTIVE
  Delivery of chitosan to subchondral bone is a novel approach for augmented marrow stimulation. We evaluated the effect of 3 presolidified chitosan-blood implant formulations on osteochondral repair progression compared with untreated defects.
  
  
  METHODS
  In N = 5 adult sheep, six 2-mm diameter Jamshidi biopsy holes were created bilaterally in the medial femoral condyle and treated with presolidified chitosan-blood implant with fluorescent chitosan tracer (10 kDa, 40 kDa, or 150k Da chitosan, left knee) or left to bleed (untreated, right knee). Implant residency and osteochondral repair were assessed at 1 day (N = 1), 3 weeks (N = 2), or 3 months (N = 2) postoperative using fluorescence microscopy, histomorphometry, stereology, and micro-computed tomography.
  
  
  RESULTS
  Chitosan implants were retained in 89% of treated Jamshidi holes up to 3 weeks postoperative. At 3 weeks, biopsy sites were variably covered by cartilage flow, and most bone holes contained cartilage flow fragments and heterogeneous granulation tissues with sparse leukocytes, stromal cells, and occasional adipocytes (volume density 1% to 3%). After 3 months of repair, most Jamshidi bone holes were deeper, remodeling at the edges, filled with angiogenic granulation tissue, and lined with variably sized chondrogenic foci fused to bone trabeculae or actively repairing bone plate. The 150-kDa chitosan implant elicited more subchondral cartilage formation compared with 40-kDa chitosan-treated and control defects (P < 0.05, N = 4). Treated defects contained more mineralized repair tissue than control defects at 3 months (P < 0.05, N = 12).
  
  
  CONCLUSIONS
  Bone plate-induced chondroinduction is an articular cartilage repair mechanism. Jamshidi biopsy repair takes longer than 3 months and can be influenced by subchondral chitosan-blood implant.
authors.affiliation: Department of Clinical Studies, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Angela D
authors.initials: AD
authors.lastname: Bell
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montreal, Quebec, Canada.
authors.forename: Viorica
authors.initials: V
authors.lastname: Lascau-Coman
authors.affiliation: BioSyntech/Piramal Healthcare Canada, Montreal, Quebec, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montreal, Quebec, Canada.
authors.forename: Gaoping
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Clinical Studies, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lowerison
authors.affiliation: Department of Clinical Studies, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Hurtig
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montreal, Quebec, Canada ; Institute of Biomedical Engineering, École Polytechnique, Montreal, Quebec, Canada.
authors.forename: Caroline D
authors.initials: CD
authors.lastname: Hoemann
keywords: Jamshidi; bone plate; chitosan; chondrogenesis; coagulation; large animal model; marrow stimulation; micro–computed tomography; osteochondral repair