中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (5): 1364-1376.doi: 10.4103/NRR.NRR-D-23-01874

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

细胞外基质刚度可调生物材料可为轴突生长和再生复制优良的环境:调节轴突生长和再生的分子机制

  

  • 出版日期:2025-05-15 发布日期:2024-10-30

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Ronglin Han1 , Lanxin Luo1 , Caiyan Wei 2 , Yaru Qiao1 , Jiming Xie1 , Xianchao Pan2, * , Juan Xing1, *   

  1. 1 Department of Pathophysiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan Province, China;  2 Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan Province, China
  • Online:2025-05-15 Published:2024-10-30
  • Contact: Juan Xing, PhD, xingjuan217@swmu.edu.cn; Xianchao Pan, PhD, panxc@swmu.edu.cn.
  • Supported by:
    The work was supported by the National Natural Science Foundation of China, No. 81801241; a grant from Sichuan Science and Technology Program, No. 2023NSFSC1578; and Scientific Research Projects of Southwest Medical University, No. 2022ZD002 (all to JX).

摘要:

神经元的生长、延伸、分支以及神经网络的形成都受到细胞外基质的影响,而细胞外基质是一种由细胞分泌的蛋白质和多糖组成的复杂网络。细胞外基质除能为细胞提供物理支持外,还能提供重要的细胞机械刚度信息。在神经系统的发育过程中,细胞外基质刚度在引导神经元生长方面发挥着重要的作用,特别是在轴突延伸方面,这对神经网络的形成至关重要。在神经组织工程中,调控生物材料刚度是一种很有前途的策略,可为损伤的神经组织的修复和再生提供一个宽松的环境。最近已有研究对合成生物材料进行微调,以制造能够复制神经系统刚度分布的支架。此次综述阐明了细胞外基质刚度如何调节轴突生长和再生的分子机制,重点关注开发刚度可调生物材料模拟体内细胞外基质环境的进展,介绍其在神经修复和再生中的应用。对刚度可调生物材料的探索和优化,将极大地推动神经组织工程的发展。

https://orcid.org/0009-0003-0893-0018 (Juan Xing); https://orcid.org/0000-0002-1269-683X (Xianchao Pan) 

关键词: 细胞外基质, 刚度, 生物材料, 神经元, 轴突生长, 聚丙烯酰胺, 藻酸盐, 聚二甲基硅氧烷, 神经修复, 神经再生

Abstract:

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

Key words: alginate, axon growth, biomaterials, extracellular matrix, neural repair, neurons, neuroregeneration, polyacrylamide, polydimethylsiloxane, stiffness