title: Subchondral chitosan/blood implant-guided bone plate resorption and woven bone repair is coupled to hyaline cartilage regeneration from microdrill holes in aged rabbit knees.
abstract: OBJECTIVE
  Little is known of how to routinely elicit hyaline cartilage repair tissue in middle-aged patients. We tested the hypothesis that in skeletally aged rabbit knees, microdrill holes can be stimulated to remodel the bone plate and induce a more integrated, voluminous and hyaline cartilage repair tissue when treated by subchondral chitosan/blood implants.
  
  
  METHODS
  New Zealand White rabbits (13 or 32 months old, N = 7) received two 1.5 mm diameter, 2 mm depth drill holes in each knee, either left to bleed as surgical controls or press-fit with a 10 kDa (distal hole: 10K) or 40 kDa (proximal hole: 40K) chitosan/blood implant with fluorescent chitosan tracer. Post-operative knee effusion was documented. Repair tissues at day 0 (N = 1) and day 70 post-surgery (N = 6) were analyzed by micro-computed tomography, and by histological scoring and histomorphometry (SafO, Col-2, and Col-1) at day 70.
  
  
  RESULTS
  All chitosan implants were completely cleared after 70 days, without increasing transient post-operative knee effusion compared to controls. Proximal control holes had worse osteochondral repair than distal holes. Both implant formulations induced bone remodeling and improved lateral integration of the bone plate at the hole edge. The 40K implant inhibited further bone repair inside 50% of the proximal holes, while the 10K implant specifically induced a "wound bloom" reaction, characterized by decreased bone plate density in a limited zone beyond the initial hole edge, and increased woven bone (WB) plate repair inside the initial hole (P = 0.016), which was accompanied by a more voluminous and hyaline cartilage repair (P < 0.05 vs control defects).
  
  
  CONCLUSIONS
  In a challenging aged rabbit model, bone marrow-derived hyaline cartilage repair can be promoted by treating acute drill holes with a biodegradable subchondral implant that elicits bone plate resorption followed by anabolic WB repair within a 70-day repair period.
authors.affiliation: Department of Chemical Engineering, École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, Canada H3C 3A7. Electronic address: jessica.guzman-morales@polymtl.ca.
authors.forename: J
authors.initials: J
authors.lastname: Guzmán-Morales
authors.affiliation: Institute of Biomedical Engineering, École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, Canada H3C 3A7. Electronic address: charles-hubert.lafantaisie-favreau@polymtl.ca.
authors.forename: C-H
authors.initials: CH
authors.lastname: Lafantaisie-Favreau
authors.affiliation: Department of Chemical Engineering, École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, Canada H3C 3A7. Electronic address: gaoping.chen@polymtl.ca.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering, École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, Canada H3C 3A7; Institute of Biomedical Engineering, École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, Canada H3C 3A7; Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), École Polytechnique, C.P. 6079 succ. Centre-Ville, Montréal, QC, Canada H3C 3A7. Electronic address: caroline.hoemann@polymtl.ca.
authors.forename: C D
authors.initials: CD
authors.lastname: Hoemann
mesh_terms: D020341:Absorbable Implants; D000375:Aging / Q000502:physiology; D000818:Animals; D001672:Biocompatible Materials; D001777:Blood Coagulation; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D048271:Chitosan / Q000494:pharmacology*; D006132:Growth Plate / Q000503:physiopathology*; D051457:Hyaline Cartilage / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D008863:Microspheres; D016348:Osseointegration; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D048271:Chitosan
keywords: Bone marrow stimulation; Bone remodeling; Cartilage repair; Chitosan particles; Implant; Subchondral bone plate