Antioxidant MnO2 nanozymes-encapsulated hydrogel synergistically regulate the spinal ROS microenvironment and promote spinal cord repair
Antioxidant MnO2 nanozymes-encapsulated hydrogel synergistically regulate the spinal ROS microenvironment and promote spinal cord repair
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DOI：
10.1016/j.cej.2023.147148
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发表时间：
2023-11
影响因子：
15.1
通讯作者：
Rangrang Fan;Di Chuan;Zhiyong Liu;Hong-xu Chen;Caili Chen;Gang Guo;Jianguo Xu
中科院分区：
文献类型：
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作者：
Rangrang Fan;Di Chuan;Zhiyong Liu;Hong-xu Chen;Caili Chen;Gang Guo;Jianguo Xu
创伤性脊髓损伤（Traumatic spinal cord injury，SCI）通常导致神经元死亡和轴突破坏，导致长期功能障碍、永久性功能障碍、显著的生活需求和巨大的经济负担。因此，SCI恢复的一个关键方面在于了解如何抑制神经干细胞（NSC）死亡，调节脊髓微环境并促进神经元和轴突的再生。在此，我们设计了多巴胺（DA）修饰的透明质酸（HA）与CeCl 3分子的桥接，称为CHD水凝胶。为了赋予水凝胶再生特性，我们掺入二甲双胍（Met）和二氧化锰（MnO 2）以形成MnO 2/Met@CHD水凝胶。MnO 2/Met@CHD水凝胶可促进神经干细胞贴壁生长和神经组织桥接，并在病理性ROS微环境中促进神经元分化和突起生长，表明其具有良好的抗氧化应激作用。此外，MnO 2/Met@CHD水凝胶可以促进nestin+ NSC的迁移和积累，并抑制GFAP+星形胶质细胞瘢痕形成，从而为轴突再生提供优化的微环境。总的来说，MnO 2/Met@CHD水凝胶系统显示出作为治疗SCI的新方法的巨大前景。
Traumatic spinal cord injury (SCI) usually leads to neuronal death and axon destruction, resulting in long-term dysfunction, permanent functional impairment, significant caregiving demands, and substantial financial burden. Therefore, a crucial aspect of SCI recovery lies in understanding how to inhibit neural stem cell (NSC) death, regulate the spinal microenvironment and promote the regeneration of neurons and axons. Herein, we designed dopamine (DA)-modified hyaluronic acid (HA) with the bridging of CeCl3molecules, termed the CHD hydrogel. To confer regenerative properties to the hydrogel, we incorporated metformin (Met) and manganese dioxide (MnO2) to form the MnO2/Met@CHD hydrogel. The MnO2/Met@CHD hydrogel could promote the NSC adhesive growth and nerve tissue bridging, and improve neuronal differentiation and neurite outgrowth in a pathological ROS microenvironment, suggesting its excellent effect against oxidative stress. Furthermore, the MnO2/Met@CHD hydrogel can facilitate the migration and accumulation of nestin+NSCs and inhibit GFAP+astrocytic scar formation, thereby providing optimized microenvironments for axonal regeneration. Collectively, the MnO2/Met@CHD hydrogel system shows great promise as a novel approach for the treatment of SCI.