使用细胞外基质启发的天然水凝胶支架促进骨软骨修复与透明软骨形成  

Enhanced osteochondral repair with hyaline cartilage formation using anextracellular matrix-inspired natural scaffold

作　　者：代文立 程锦 闫文强 曹宸喜 赵逢源 李琪 胡晓青 王健全 敖英芳 Wenli Dai;Jin Cheng;Wenqiang Yan;Chenxi Cao;Fengyuan Zhao;Qi Li;Xiaoqing Hu;Jianquan Wang;Yingfang Ao(Beijing Key Laboratory of Sports Injuries,Institute of Sports Medicine of Peking University,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]Beijing Key Laboratory of Sports Injuries,Institute of Sports Medicine of Peking University,Peking University Third Hospital,Beijing 100191,China

出　　处：《Science Bulletin》2023年第17期1904-1917,共14页科学通报（英文版）

基　　金：supported by the National Key Research and Development Program of China(2018YFF0301100);the National Natural Science Foundation of China(82172420 and 82202723)。

摘　　要：骨软骨缺损是一个巨大的挑战,目前临床上尚未确定满意的修复策略.尤其是不恰当的修复方法可能导致纤维软骨和软骨下骨的生成,从而导致骨软骨组织的退化,最终导致修复失败.本研究受天然细胞外基质(extracellular matrix,ECM)中固有的化学成分的启发,提出了一种由天然多糖和多肽组成的新型仿生ECM支架,用于骨软骨修复.通过对天然生物聚合物进行修饰改性,形成具有可逆的客体-主体网络和刚性的共价网络的双网络结构,该支架不仅表现出优秀的生物相容性、细胞适应性和生物可降解性,还具有卓越的机械性能以适应骨软骨组织的环境.在兔的骨软骨缺损中,这种受ECM启发的支架不仅展示了强大的促进透明软骨形成的能力,还加速了具有优良骨密度的软骨下骨的再生.此外,新生的软骨和软骨下骨表现出了天然软骨的异质性特征,模拟了软骨到软骨下骨的渐进过渡.这些结果突显了该新型仿生ECM支架在临床应用中的潜在价值.Osteochondral defects pose a great challenge and a satisfactory strategy for their repair has yet to be identified.In particular,poor repair could result in the generation of fibrous cartilage and subchondral bone,causing the degeneration of osteochondral tissue and eventually leading to repair failure.Herein,taking inspiration from the chemical elements inherent in the natural extracellular matrix(ECM),we proposed a novel ECM-mimicking scaffold composed of natural polysaccharides and polypeptides for osteochondral repair.By meticulously modifying natural biopolymers to form reversible guest–host and rigid covalent networks,the scaffold not only exhibited outstanding biocompatibility,cell adaptability,and biodegradability,but also had excellent mechanical properties that can cater to the environment of osteochondral tissue.Additionally,benefiting from the drug-loading group,chondrogenic and osteogenic drugs could be precisely integrated into the specific zone of the scaffold,providing a tissue-specific microenvironment to facilitate bone and cartilage differentiation.In rabbit osteochondral defects,the ECM-inspired scaffold not only showed a strong capacity to promote hyaline cartilage formation with typical lacuna structure,sufficient mechanical strength,good elasticity,and cartilage-specific ECM deposition,but also accelerated the regeneration of quality subchondral bone with high bone mineralization density.Furthermore,the new cartilage and subchondral bone were heterogeneous,a trait that is typical of the natural landscape,reflecting the gradual progression from cartilage to subchondral bone.These results suggest the potential value of this bioinspired osteochondral scaffold for clinical applications.

关 键 词：透明软骨 软骨下骨 骨软骨 纤维软骨 细胞外基质 生物可降解性 生物聚合物 天然多糖 

分 类 号：TQ427.26[化学工程] R318.08[医药卫生—生物医学工程]