Bioactive fiber-reinforced hydrogel to tailor cell microenvironment for structural and functional regeneration of myotendinous junction

作者：Yuzhi Sun, Renwang Sheng, Zhicheng Cao, Chuanquan Liu, Jiaxiang Li, Po Zhang, Yan Du, Qingyun Mo, Qingqiang Yao, Jialin Chen, Wei Zhang · 发表于：Science Advances · 年份：2024 · DOI：10.1126/sciadv.adm7164 · 被引用次数：67 · 研究领域：Tendon Structure and Treatment、Knee injuries and reconstruction techniques、Tissue Engineering and Regenerative Medicine

Myotendinous junction (MTJ) injuries are prevalent in clinical practice, yet the treatment approaches are limited to surgical suturing and conservative therapy, exhibiting a high recurrence rate. Current research on MTJ tissue engineering is scarce and lacks in vivo evaluation of repair efficacy. Here, we developed a three-dimensional-printed bioactive fiber-reinforced hydrogel containing mesenchymal stem cells (MSCs) and Klotho for structural and functional MTJ regeneration. In a rat MTJ defect model, the bioactive fiber-reinforced hydrogel promoted the structural restoration of muscle, tendon, and muscle-tendon interface and enhanced the functional recovery of injured MTJ. In vivo proteomics and in vitro cell cultures elucidated the regenerative mechanisms of the bioactive fiber-reinforced hydrogel by modulating oxidative stress and inflammation, thus engineering an optimized microenvironment to support the survival and differentiation of transplanted MSCs and maintain the functional phenotype of resident cells within MTJ tissues, including tendon/muscle cells and macrophages. This strategy provides a promising treatment for MTJ injuries.