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

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...

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Bibliographic Details
Published in:Neural regeneration research 2025-05, Vol.20 (5), p.1364-1376
Main Authors: Han, Ronglin, Luo, Lanxin, Wei, Caiyan, Qiao, Yaru, Xie, Jiming, Pan, Xianchao, Xing, Juan
Format: Article
Language:English
Subjects:
alginate
axon growth
biomaterials
Biomedical materials
Extracellular matrix
Nervous system
Neural networks
neural repair
neurons
neuroregeneration
polyacrylamide
polydimethylsiloxane
Review
stiffness
Tissue engineering
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Summary: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.
ISSN:1673-5374
1876-7958
DOI:10.4103/NRR.NRR-D-23-01874