Evaluation of Genipin for Stabilization of Decellularized Porcine Cartilage

Evaluation of Genipin for Stabilization of Decellularized Porcine Cartilage
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DOI:
10.1002/jor.23483
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发表时间:
2017-09-01
影响因子:
2.8
通讯作者:
Wright, Emily
Wright, Emily
中科院分区:
医学3区
文献类型:
--
作者:
Elder, Steven;Pinheiro, Amanda;Wright, Emily

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我们推测,脱细胞骨软骨异种移植物可能是修复局灶性关节软骨损伤的同种异体移植物的良好替代品。为了使异种移植物抵抗酶促降解并防止慢性免疫反应,通过交联使其稳定可能是有益的。该概念类似于用戊二醛处理猪生物假体心脏瓣膜。本研究的目的是评估京尼平(一种具有低细胞毒性的天然交联剂)对脱细胞软骨的稳定作用。将猪关节软骨盘在 SDS 和核酸酶中脱细胞,然后在京尼平中交联。京尼平的效用取决于其对交联度、机械性能、尺寸稳定性、酶抗性和体外生物相容性的影响。交联度、压缩模量和胶原酶抗性在很大范围内变化,具体取决于京尼平浓度。平衡压缩模量可以从天然软骨的约50%增加到120%以上,胶原酶完全降解的时间可以从不到12小时延长到15天以上。在0.1%重量/体积的京尼平浓度下观察到约4%的径向收缩,并且软骨与玻璃的摩擦系数以浓度依赖性方式增加。在培养 6 周期间,与非交联软骨相比,自体软骨细胞的活力或在京尼平固定软骨表面附着和扩散的能力几乎没有差异。这些结果表明京尼平对于稳定脱细胞猪骨软骨异种移植物可能有效。 (c) 2017 年骨科研究学会。由 Wiley 期刊公司出版
We speculate that an acellular osteochondral xenograft may be a good alternative to allografts for repair of focal articular cartilage lesions. In order to make a xenograft resistant to enzymatic degradation and to prevent a chronic immune response it may be beneficial to stabilize it through crosslinking. The concept is analogous to treatment of porcine bioprosthetic heart valves with glutaraldehyde. The purpose of this study was to evaluate genipin, a natural crosslinking agent with low cytotoxicity, for stabilization of decellularized cartilage. Porcine articular cartilage discs were decellularized in SDS and nucleases and then crosslinked in genipin. The utility of genipin was determined from its effects on degree of crosslinking, mechanical properties, dimensional stability, enzymatic resistance, and in vitro biocompatibility. Degree of crosslinking, compressive moduli, and collagenase resistance varied over a wide range depending on genipin concentration. The equilibrium compressive modulus could be increased from approximately 50% to more than 120% that of native cartilage, and the time to complete degradation by collagenase could be extended from less than 12 h to more than 15 days. Radial shrinkage of approximately 4% was observed at a genipin concentration of 0.1% wt/vol, and cartilage coefficient of friction against glass increased in a concentration-dependent manner. Autologous chondrocytes displayed little difference in viability or their ability to attach and spread over the surface of genipin-fixed cartilage compared to non-crosslinked cartilage during 6 weeks of culture. These results indicate that genipin may be efficacious for stabilization of a decellularized porcine osteochondral xenograft. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.