A tannic acid doped hydrogel with small extracellular vesicles derived from mesenchymal stem cells promotes spinal cord repair by regulating reactive oxygen species microenvironment.
A tannic acid doped hydrogel with small extracellular vesicles derived from mesenchymal stem cells promotes spinal cord repair by regulating reactive oxygen species microenvironment.
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DOI：
10.1016/j.mtbio.2022.100425
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发表时间：
2022-12
影响因子：
8.2
通讯作者：
Fu, Qiang
中科院分区：
文献类型：
--
作者：
Liu, Zhong;Guo, Song;Dong, Lanlan;Wu, Peipei;Li, Kewei;Li, Xinhua;Li, Xiang;Qian, Hui;Fu, Qiang
关键词：
脊髓损伤（SCI）是一种严重的中枢神经系统疾病，预后不良;此外，现有的临床治疗不能以有效的方式恢复神经功能。炎症反应和损伤微环境中活性氧（ROS）的产生增加是抑制SCI恢复的主要障碍。来源于间充质干细胞的小细胞外囊泡（sEVs）是无细胞治疗的合适选择，并已被证明在SCI中发挥治疗作用，从而为微环境调节提供了潜在的策略。然而，小细胞外囊泡的有效保留、控制释放和整合到受损的脊髓组织中仍然是一个重大挑战。本文中，我们制备了具有可持续sEV释放（sEVs-NGL/T）的N-丙烯酰甘氨酰胺/明胶甲基丙烯酸酯/Laponite/单宁酸（那牙/GelMA/LPN/TA，NGL/T）水凝胶，以促进SCI后运动功能的恢复。新开发的功能性sEVs-NGL/T水凝胶在体外H2 O2模拟过氧化微环境中表现出优异的抗氧化性能。体内植入功能性sEVs-NGL/T水凝胶可以包裹sEV，表现出有效的保留和sEV的持续释放，从而协同诱导运动功能的显著恢复和泌尿组织的保护。这些积极作用可归因于炎症和ROS微环境的有效缓解。因此，sEVs-NGL/T疗法为基于sEV的治疗SCI提供了一个有希望的策略，通过全面调节病理微环境。
Spinal cord injury (SCI) is a serious disease of the central nervous system that is associated with a poor prognosis; furthermore, existing clinical treatments cannot restore nerve function in an effective manner. Inflammatory responses and the increased production of reactive oxygen species (ROS) in the microenvironment of the lesion are major obstacles that inhibit the recovery of SCI. Small extracellular vesicles (sEVs), derived from mesenchymal stem cells, are suitable options for cell-free therapy and have been shown to exert therapeutic effects in SCI, thus providing a potential strategy for microenvironment regulation. However, the effective retention, controlled release, and integration of small extracellular vesicles into injured spinal cord tissue are still a major challenge. Herein, we fabricated an N-acryloyl glycinamide/gelatin methacrylate/Laponite/Tannic acid (NAGA/GelMA/LPN/TA, NGL/T) hydrogel with sustainable sEV release (sEVs-NGL/T) to promote the recovery of motor function after SCI. The newly developed functional sEVs-NGL/T hydrogel exhibited excellent antioxidant properties in an H2O2-simulated peroxidative microenvironment in vitro. Implantation of the functional sEVs-NGL/T hydrogel in vivo could encapsulate sEVs, exhibiting efficient retention and the sustained release of sEVs, thereby synergistically inducing significant restoration of motor function and urinary tissue preservation. These positive effects can be attributed to the effective mitigation of the inflammatory and ROS microenvironment. Therefore, sEVs-NGL/T therapy provides a promising strategy for the sEV-based therapy in the treatment of SCI by comprehensively regulating the pathological microenvironment.
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