Abstract
BackgroundIn 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.MethodsThree 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.ResultsAll 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.ConclusionsPre-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.
Highlights
In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits
This study demonstrated that subchondral chitosan implants sequentially draw neutrophils and undifferentiated bone marrow-derived stromal cells into drilled bone defects, which was accompanied by osteoclast formation and bone remodeling
This study has demonstrated that pre-solidified TFchitosan-Sodium chloride (NaCl)/blood implants can be successfully retained in microdrill holes, become partly cleared, and elicit neutrophils followed by bone marrow-derived stromal cells at 21 days in a skeletally aged rabbit model of cartilage repair
Summary
In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. Biomaterials have previously been successfully implanted into osteochondral defects, but reproducible long-term clinical benefits have yet to be demonstrated. A tubular implant composed of electrospun poly(D,L-lactide-co-glycolide) (PLG) inserted in large (5 mm wide, 5 mm deep) osteochondral defects in a rabbit model generated good cartilage repair in most defects at 24 weeks post-operative [3]. In a rabbit model, filling the drill hole with a chemically cross-linked chitosan hydrogel was previously shown to block cell infiltration and bone repair [7]. These data suggest that the porosity and degradation kinetics of biomaterials implanted in subchondral bone are key elements in the induction of reproducible osteochondral repair
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