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.Design: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.

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

“…From a clinical standpoint, the present study and previous investigations in small animal models192243 show that the balance of bone turnover is clearly shifted to bone resorption at this very early phase, the first several weeks of cartilage repair following microfracture. The finding of the present study that osteoclast density is higher in both microfracture groups compared with debridement alone is in good agreement with the work of Chen et al ., supporting the important role of osteoclasts as cellular mediators of marrow stimulation techniques that incise the subchondral bone22.…”

“…Hoemann et al . proved that new bone formation already started at 2 weeks following the marrow stimulation in a rabbit model, accompanied by a high activity of osteoclasts, serving as cellular mediators of marrow-derived cartilage repair22. However, the very early effects of microfracture on the subchondral bone in a large animal model remain unknown to date.…”

Characterization of Subchondral Bone Repair for Marrow-Stimulated Chondral Defects and Its Relationship to Articular Cartilage Resurfacing

“…Previous studies have shown that a higher level of bone remodeling activity is one of the main factors supporting improved cartilage repair during stimulation of the repair process using biomaterials. 4,5,8,17,18 The presence of a remodeled and porous subchondral bone plate was also previously associated with more hyaline tissue repair and Figure 5. Characterization of the extent of repaired and remodeling subchondral bone in trochlear defects that received marrow stimulation.…”

Characterization of Initial Microfracture Defects in Human Condyles

“…Bone marrow cells are also altered by smoking, and aging, which could also limit the repair response to MFX. 5,22,26,44 Our data suggest that uniform debridement of approximately 200 µm of mineralized tissue should be sufficient to remove the calcified cartilage layer in most lesions, including Grade IV lesions. Curettage offers a tactile appreciation of the "grating" away of mineralized tissue but is time-consuming, nonuniform, and can lead to iatrogenic damage of surrounding cartilage.…”