Yan Dan, Zhou Guangdong, Zhou Xu, Liu Wei, Zhang Wen Jie, Luo Xusong, Zhang Lu, Jiang Ting, Cui Lei, Cao Yilin
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 Zhi Zao Ju Road, Shanghai 200011, PR China.
Biomaterials. 2009 Feb;30(5):814-21. doi: 10.1016/j.biomaterials.2008.10.042. Epub 2008 Nov 25.
The application of in vitro engineered cartilage has become a promising approach to repair cartilage defects. Nevertheless, the poor mechanical properties of in vitro engineered cartilage limit its potential for clinical applications. Studies have shown that the extracellular matrix (ECM) components are strongly correlated with the mechanical strength of engineered cartilage, but it remains unclear which components play a key role in determining the mechanical property of engineered cartilage. To address this issue, quantitative analyses of cartilage-specific components among native cartilage, in vivo and in vitro engineered cartilages were performed, and the correlation between various ECM molecules and Young's modulus was further analyzed. The results showed that many ECM molecules, such as highly sulphated glycosaminoglycan (GAG), collagens II, IX, and pyridinoline (PYR), contributed to the mechanical strength of cartilages. Further comparison between in vitro engineered cartilage and stress-stimulated in vitro engineered cartilage, known to have stronger mechanical properties, showed that only collagen IX and PYR, but not GAG and collagen II, were the key factors determining the mechanical properties of in vitro engineered cartilage. These results indicate that in vitro environment lacks the niche for enhancing collagen crosslinking that is mediated by collagen IX and PYR during cartilage formation. Thus, the discovery provides a clue for engineering strong cartilage in vitro in the future by enhancing the levels of these two molecules.
体外工程化软骨的应用已成为修复软骨缺损的一种有前景的方法。然而，体外工程化软骨较差的力学性能限制了其临床应用潜力。研究表明，细胞外基质（ECM）成分与工程化软骨的力学强度密切相关，但尚不清楚哪些成分在决定工程化软骨的力学性能中起关键作用。为解决这一问题，对天然软骨、体内和体外工程化软骨中的软骨特异性成分进行了定量分析，并进一步分析了各种ECM分子与杨氏模量之间的相关性。结果表明，许多ECM分子，如高度硫酸化的糖胺聚糖（GAG）、胶原蛋白II、IX和吡啶啉（PYR），对软骨的力学强度有贡献。进一步比较体外工程化软骨和已知具有更强力学性能的应力刺激体外工程化软骨，结果表明，只有胶原蛋白IX和PYR，而不是GAG和胶原蛋白II，是决定体外工程化软骨力学性能的关键因素。这些结果表明，体外环境缺乏在软骨形成过程中由胶原蛋白IX和PYR介导的增强胶原蛋白交联的微环境。因此，这一发现为未来通过提高这两种分子的水平在体外构建高强度软骨提供了线索。
