Zheng Lixia, Li Dejian, Wang Weizhong, Zhang Qianqian, Zhou Xiaojun, Liu Dinghua, Zhang Jingtian, You Zhengwei, Zhang Jundong, He Chuanglong
Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201301, China.
Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, China.
ACS Biomater Sci Eng. 2019 Sep 9;5(9):4564-4573. doi: 10.1021/acsbiomaterials.9b00513. Epub 2019 Aug 16.
Recently, a bilayered scaffold with an anisotropic structure mimicking a native osteochondral tissue shows considerable potential for treating osteochondral defects. Herein, a bilayered scaffold consisting of biomimetic cartilage and a subchondral bone architecture was constructed for repairing osteochondral defect. A hydrogel prepared by the Schiff base reaction of gelatin, silk fibroin, and oxidized dextran was designed as the cartilage layer, while a nanofibrous scaffold with a macroporous structure prepared from the polymer blend of poly(l-lactic acid)/poly(lactic--glycolic acid)/poly(ε-caprolactone) using the dual phase separation technique served as a subchondral layer. The subchondral layer was then treated with polydopamine coating for osteogenic factor immobilization. To facilitate the chondrogenic and osteogenic differentiation of bone marrow mesenchymal stem cells on the bilayered scaffold, the cartilage-inducing drug kartogenin (KGN) and osteogenic-inducing factor bone morphogenetic protein 2-derived peptides (P24 peptides) were, respectively, loaded on the subchondral layer. Next, the in vitro release of KGN and P24 peptide from the corresponding layer was monitored, respectively, and the results showed that both the release time of KGN and P24 peptides would last for more than 28 days. The in vitro results indicated that the KGN-loaded cartilage layer and P24 peptides-loaded subchondral layer were capable of supporting cell proliferation, and induced the chondrogenic and osteogenic differentiation, respectively. Furthermore, the in vivo experiments suggested that the bilayered scaffold significantly accelerated the regeneration of the osteochondral tissue in the rabbit knee joint model. Consequently, this bilayered scaffold loaded with KGN and P24 peptides would be a promising candidate for repairing osteochondral defect.
最近，一种具有模仿天然骨软骨组织各向异性结构的双层支架在治疗骨软骨缺损方面显示出巨大潜力。在此，构建了一种由仿生软骨和软骨下骨结构组成的双层支架用于修复骨软骨缺损。通过明胶、丝素蛋白和氧化葡聚糖的席夫碱反应制备的水凝胶被设计为软骨层，而使用双相分离技术由聚（L-乳酸）/聚（乳酸-乙醇酸）/聚（ε-己内酯）的聚合物共混物制备的具有大孔结构的纳米纤维支架用作软骨下层。然后用聚多巴胺涂层处理软骨下层以固定成骨因子。为了促进骨髓间充质干细胞在双层支架上的软骨生成和成骨分化，分别将软骨诱导药物卡托金（KGN）和成骨诱导因子骨形态发生蛋白2衍生肽（P24肽）加载到软骨下层上。接下来，分别监测KGN和P24肽从相应层的体外释放情况，结果表明KGN和P24肽的释放时间均持续超过28天。体外结果表明，负载KGN的软骨层和负载P24肽的软骨下层能够支持细胞增殖，并分别诱导软骨生成和成骨分化。此外，体内实验表明，双层支架显著加速了兔膝关节模型中骨软骨组织的再生。因此，这种负载KGN和P24肽的双层支架有望成为修复骨软骨缺损的候选材料。
