A DAMP-scavenging, IL-10-releasing hydrogel promotes neural regeneration and motor function recovery after spinal cord injury
A DAMP-scavenging, IL-10-releasing hydrogel promotes neural regeneration and motor function recovery after spinal cord injury
复制标题
清湿、释放IL-10水凝胶促进脊髓损伤后神经再生和运动功能恢复
DOI：
10.1016/j.biomaterials.2021.121279
复制
发表时间：
2021-11-27
期刊：
影响因子：
14
通讯作者：
Dai, Jianwu
中科院分区：
文献类型：
--
作者：
Shen, He;Xu, Bai;Dai, Jianwu
脊髓损伤（SCI）产生了一种炎症微环境，其特征是损伤相关分子模式（DAMP）和免疫细胞活化，加剧了继发性损伤并损害神经恢复。在这里，我们开发了一种用于治疗SCI的免疫调节性水凝胶支架，其清除DAMP并缓慢释放抗炎细胞因子白细胞介素-10（IL-10）。我们通过用阳离子、DAMP结合聚合物聚（酰胺基胺）和IL-10修饰光交联明胶水凝胶来创建这种双功能支架，并将这种支架的治疗活性与仅明胶、明胶+聚（酰胺基胺）和明胶+ IL-10支架的治疗活性在体外和体内进行比较。在体外，双功能支架清除阴离子DAMPs，并表现出持续释放IL-10，减少巨噬细胞和小胶质细胞的促炎反应，并增强神经干细胞的神经源性分化。在完全横断SCI小鼠模型中，注射的双功能支架抑制促炎细胞因子的产生，促进M2巨噬细胞/小胶质细胞表型，并导致神经再生和轴突生长，而不形成瘢痕，其程度大于单功能或对照支架。这种清除DAMP、释放IL-10的支架为促进严重SCI后的神经再生和运动功能恢复提供了新的策略。
Spinal cord injury (SCI) creates an inflammatory microenvironment characterized by damage-associated molecular patterns (DAMPs) and immune cell activation that exacerbate secondary damage and impair neurological recovery. Here we develop an immunoregulatory hydrogel scaffold for treating SCI that scavenges DAMPs and slowly releases the anti-inflammatory cytokine interleukin-10 (IL-10). We created this dual-functional scaffold by modifying a photocrosslinked gelatin hydrogel with the cationic, DAMP-binding polymer poly (amidoamine) and with IL-10, and compared the therapeutic activity of this scaffold with that of gelatin-only, gelatin + poly (amidoamine), and gelatin + IL-10 scaffolds in vitro and in vivo. In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibited sustained release of IL-10, reduced the proinflammatory responses of macrophages and microglia, and enhanced the neurogenic differentiation of neural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressed proinflammatory cytokine production, promoted the M2 macrophage/microglia phenotype, and led to neural regeneration and axon growth without scar formation to a greater extent than the single-function or control scaffolds. This DAMP-scavenging, IL-10-releasing scaffold provides a new strategy for promoting neural regeneration and motor function recovery following severe SCI.