再生(生物学)
雪旺细胞
重编程
神经导管
周围神经
细胞生物学
坐骨神经
外周神经系统
神经外膜修复
自愈水凝胶
周围神经损伤
材料科学
解剖
生物物理学
细胞
神经科学
化学
生物
医学
高分子化学
生物化学
中枢神经系统
作者
Shuai Han,Laiben Gao,Xiaoqiu Dou,Zhengguang Wang,Kaikai Yang,Dongdong Li,Yusong Yuan,Chao Xing,Baoguo Jiang,Yun Tian,Chuanliang Feng,Peixun Zhang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-10-07
卷期号:18 (41): 28358-28370
标识
DOI:10.1021/acsnano.4c10653
摘要
The Schwann cell (SC) is essential in peripheral nerve regeneration by reprogramming into a stem-like "repair Schwann cell" (rSC) phenotype; however, maintaining the rSC stemness remains an unmet challenge. Chirality is a fundamental factor controlling cell fate, and its potential role in regulation of SC reprogramming has long been ignored and remains poorly understood. Herein, inspired by natural chiral components in the SC microenvironment, chiral hydrogel nerve conduits are prepared by supramolecular assembly of l/d-phenylalanine derivatives (l/d-Phe) in polymeric chitosan-gelatin conduits. Right-handed l-Phe fibers within hydrogel conduits maintain the stemness of rSC through enhanced stereoselective interaction between collagen IV and l-Phe fibers triggered by collagen IV-Integrin α1β1, MAPK, and YAP/TAZ signaling pathways and finally activate the key regulator of SC reprogramming, the c-Jun pathway. In the rat model of a sciatic nerve defect, the l-Phe hydrogel nerve conduit significantly enhances nerve regeneration, exhibiting markedly improved histological, electrophysiological, and functional outcomes. The findings reveal the chirality-dependent regulation of SC reprogramming in a pioneering way, offering potential strategies for nerve regeneration therapies.
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