Thermosensitive hydrogel‐based GPR124 delivery strategy for rebuilding blood‐spinal cord barrier

作者：Jiawei Shu, Chenggui Wang, Yiqing Tao, Shaoke Wang, Feng Cheng, Yuang Zhang, Kesi Shi, Kaishun Xia, Ronghao Wang, Jingkai Wang, Chao Yu, Jiangjie Chen, Xianpeng Huang, Haibin Xu, Xiaopeng Zhou, Haobo Wu, Chengzhen Liang, Qixin Chen, Shigui Yan, Fangcai Li · 发表于：Bioengineering & Translational Medicine · 年份：2023 · DOI：10.1002/btm2.10561 · 被引用次数：11 · 研究领域：Spinal Cord Injury Research、Nerve injury and regeneration、Neuropeptides and Animal Physiology

Spinal cord injury (SCI) causes blood-spinal cord barrier (BSCB) disruption, leading to secondary damage, such as hemorrhagic infiltration, inflammatory response, and neuronal cell death. It is of great significance to rebuild the BSCB at the early stage of SCI to alleviate the secondary injury for better prognosis. Yet, current research involved in the reconstruction of BSCB is insufficient. Accordingly, we provide a thermosensitive hydrogel-based G protein-coupled receptor 124 (GPR124) delivery strategy for rebuilding BSCB. Herein, we firstly found that the expression of GPR124 decreased post-SCI and demonstrated that treatment with recombinant GPR124 could partially alleviate the disruption of BSCB post-SCI by restoring tight junctions (TJs) and promoting migration and tube formation of endothelial cells. Interestingly, GPR124 could also boost the energy metabolism of endothelial cells. However, the absence of physicochemical stability restricted the wide usage of GPR124. Hence, we fabricated a thermosensitive heparin-poloxamer (HP) hydrogel that demonstrated sustained GPR124 production and maintained the bioactivity of GPR124 (HP@124) for rebuilding the BSCB and eventually enhancing functional motor recovery post-SCI. HP@124 hydrogel can encapsulate GPR124 at the lesion site by injection, providing prolonged release, preserving wounded tissues, and filling injured tissue cavities. Consequently, it induces synergistically efficient integrated regulation by blocking BSCB ru...