Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.
BioSyntech Canada Inc., Laval, Quebec, Canada ; Piramal Healthcare (Canada), Laval, Quebec, Canada Institution where the work reported was done: Ecole Polytechnique, Montreal, Quebec, Canada.
Cartilage. 2011 Apr;2(2):173-85. doi: 10.1177/1947603510381096.
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.
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.
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).
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.
软骨-骨整合是软骨修复治疗的一个重要功能终点，但对于如何促进整合知之甚少。我们假设壳聚糖稳定的血凝块植入物会引发破骨细胞进入钻孔软骨缺损，并促进修复和软骨-骨整合，对此进行了测试。
在 15 只成熟的兔膝关节的滑车双侧缺陷处进行微钻孔，然后用壳聚糖-甘油磷酸（GP）/含荧光壳聚糖示踪剂和凝血酶的血液植入物处理，以加速原位固化，或单独用凝血酶处理。在 1、2 和 8 周时，在外、边缘和通过近端微钻孔处评估壳聚糖清除率、破骨细胞密度和骨软骨修复情况。
壳聚糖在第 1 周保留在钻孔的顶部，在第 2 周成为肉芽组织细胞内的细胞外颗粒，在第 8 周完全清除。破骨细胞在第 1 周时在微钻孔边缘爆裂聚集，在第 2 周时在钻孔底部的新编织骨中聚集，在第 8 周时在软骨下的软骨修复下聚集。与对照组相比，植入物引起的破骨细胞增加了 2 倍（P < 0.001），钻孔骨修复更完整，并改善了软骨-骨整合和组织学组织质量。治疗组和对照组 8 周的软骨修复组织中含有 85%的 II 型胶原。在修复 8 周后，软骨下破骨细胞密度与骨-软骨修复组织整合呈正相关（P < 0.0005）。
壳聚糖-GP/血液植入物通过间接机制放大了软骨下破骨细胞的急性涌入，从而显著改善了修复和软骨-骨整合，而不会引起净骨吸收。破骨细胞是骨髓来源的软骨修复整合的细胞介导者。
