A bioinspired mineralized collagen scaffold promotes enthesis healing and activates Gli1 expression in preclinical models

作者：Tao Zhang, Tingyun Lei, Jie Han, Yangwu Chen, Yan-Chai Nie, Ru Zhang, Honglu Cai, Zijin Guo, Ruojin Yan, Zan Li, Yongqiang Xu, Xianzhu Zhang, Hongxia Xu, Jiahe Chen, Youguo Liao, Qiulin He, Hong Zhang, Jianquan Chen, Shouan Zhu, Jiansheng Guo, Yi Liu, Haihua Pan, Jingyao Chen, Wei Yin, Hongwei Ouyang, Weiliang Shen, Zi Yin, Ruikang Tang, Xiao Chen · 发表于：Science Translational Medicine · 年份：2025 · DOI：10.1126/scitranslmed.ado6948 · 被引用次数：7 · 研究领域：Tendon Structure and Treatment、Elbow and Forearm Trauma Treatment、Osteoarthritis Treatment and Mechanisms

The enthesis, a fibrocartilaginous tissue connecting tendon or ligament to bone, is critical for joint movement but lacks regenerative capacity after injury. Current clinical treatments for enthesis healing remain limited. Here, with a resolution of 2 to 3 nanometers, we found that mineral particles form a continuous cross-fibrillar phase with a discontinuous distribution in the fibrocartilage layer. Building on this finding, we developed a series of bioinspired mineralized collagen matrices, characterized by both intra- and extrafibrillar localization of crystallites, with a tunable mass percentage of inorganic content as scaffolds for enthesis repair. Our results revealed that mineralized collagen with controlled inorganic content (33% mineral content) facilitated fibrocartilage healing across multiple animal enthesis injury models, including mice, rats, rabbits, and goats. In direct comparisons with other biomaterials in a rabbit model, the bioinspired mineralized collagen resulted in 82% fibrocartilage width recovery, more than two times the healing observed with other materials. Treatment with the bioinspired mineralized collagen scaffold produced joint healing with an ability to sustain a higher maximum load in both rat and rabbit models, with the animals able to walk normally. The goat model exhibited an improvement in jumping ability. Mechanistically, we found that the bioinspired mineralized collagen modulated Hedgehog signaling intensity in a mineralization-dependen...