title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Biomedical Engineering, École Polytechnique, C,P, 6079 succ, Centre-Ville, Montréal, QC, H3C 3A7, Canada.
authors: Charles-Hubert
authors: CH
authors: Lafantaisie-Favreau
authors: Jessica
authors: J
authors: Guzmán-Morales
authors: Jun
authors: J
authors: Sun
authors: Gaoping
authors: G
authors: Chen
authors: Adam
authors: A
authors: Harris
authors: Thomas D
authors: TD
authors: Smith
authors: Alberto
authors: A
authors: Carli
authors: Janet
authors: J
authors: Henderson
authors: William D
authors: WD
authors: Stanish
authors: Caroline D
authors: CD
authors: Hoemann
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001777:Blood Coagulation; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D002357:Cartilage Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002633:Chemotaxis; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004343:Drug Implants; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D007719:Knee Joint / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D023421:Models, Animal; D008970:Molecular Weight; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013925:Thromboplastin / Q000494:pharmacology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D004343:Drug Implants; D048271:Chitosan; D013925:Thromboplastin