A N‐Cadherin Nano‐Antagonist Hydrogel Enhances Recovery From Spinal Cord Injury by Impeding Glial Scarring

• Published in: Advanced functional materials Vol. 34; no. 39
• Main Authors: Liu, Qiuling, Peng, Sufen, Tang, Qiao, Li, Can, Chen, Jiayi, Pang, Peng, Liu, Wen, Zhou, Xiaoyan, Cai, Xianlong, Lin, Hongsheng, Xue, Wei, Ji, Xin, Ji, Zhisheng
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 30.07.2024
• Subjects: astrocyte; Barriers; Calcium ions; glial scar; Hydrogels; Inflammatory response; Injury prevention; nano‐antagonist hydrogel; N‐cadherin; Pharmacology; Regeneration; Scars; Spinal cord injuries; spinal cord injury
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202404563

The role of glial scars in the pathophysiology of spinal cord injury (SCI) is widely recognized, as they pose physical barriers against axonal regeneration and persistent chronic inflammation by releasing cytotoxic agents, thereby impeding nerve repair. Consequently, preventing glial scarring has emerged as an important therapeutic objective in SCI management. Following SCI, astrocytes undergo a phenotypic transition into scar‐forming astrocytes, which critically depends on the activation of inflammatory responses and the integrin‐N‐cadherin pathway. To explore improved SCI treatment, a nano‐antagonist hydrogel (Nano‐ant Gel), comprising N‐cadherin nano‐antagonists and a polyphenol hydrogel designed to inhibit glial scarring by mitigating inflammatory response and modulating astrocyte behavior, thereby facilitating spinal cord‐injury repair, is developed and characterized. The hydrogel exhibits notable anti‐inflammatory properties, specific calcium ion‐adsorption capabilities, and antagonistic effects against N‐cadherin, effectively impeding the formation and aggregation of scar‐forming astrocytes. Its efficacy is comprehensively assessed using a model of contusive SCI, with which it effectively inhibits glial scar formation and promotes axonal regeneration. Notably, the Nano‐ant Gel significantly improves the locomotor functions of mice with SCI, suggesting that it represents a promising approach for treating the condition. Nano‐ant Gel is developed to inhibit glial scarring and enhance SCI repair. The hydrogel modulates astrocyte behavior and mitigates neuronal damage. In a contusive SCI model, Nano‐ant Gel effectively prevents the formation of scar‐forming astrocytes and promotes axonal regeneration, resulting in significantly improved locomotor functions in mice.