Magnesium‐Encapsulated Injectable Hydrogel and 3D‐Engineered Polycaprolactone Conduit Facilitate Peripheral Nerve Regeneration

作者：Zhi Yao, Weihao Yuan, Jiankun Xu, Wenxue Tong, Jie Mi, Pak‐Cheong Ho, Dick Ho Kiu Chow, Ye Li, Hao Yao, Xu Li, Shunxiang Xu, Jiaxin Guo, Qingtang Zhu, Liming Bian, Ling Qin · 发表于：Advanced Science · 年份：2022 · DOI：10.1002/advs.202202102 · 被引用次数：142 · 研究领域：Nerve injury and regeneration、Graphene and Nanomaterials Applications、Electrospun Nanofibers in Biomedical Applications

Abstract Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold‐based tissue engineering is a promising strategy to promote nerve regeneration. Additionally, magnesium (Mg) ions enhance nerve regeneration; however, an effectively controlled delivery vehicle is necessary to optimize their in vivo therapeutic effects. Herein, a bisphosphonate‐based injectable hydrogel exhibiting sustained Mg2+ delivery for peripheral nerve regeneration is developed. It is observed that Mg2+ promoted neurite outgrowth in a concentration‐dependent manner by activating the PI3K/Akt signaling pathway and Sema5b. Moreover, implantation of polycaprolactone (PCL) conduits filled with Mg2+‐releasing hydrogel in 10 mm nerve defects in rats significantly enhanced axon regeneration and remyelination at 12 weeks post‐operation compared to the controls (blank conduits or conduits filled with Mg2+‐absent hydrogel). Functional recovery analysis reveals enhanced reinnervation in the animals treated with the Mg2+‐releasing hydrogel compared to that in the control groups. In summary, the Mg2+‐releasing hydrogel combined with the 3D‐engineered PCL conduit promotes peripheral nerve regeneration and functional recovery. Thus, a new strategy to facilitate the repai...