Theranostics 2022; 12(11):4993-5014. doi:10.7150/thno.74571 This issue


Biomechanical microenvironment in peripheral nerve regeneration: from pathophysiological understanding to tissue engineering development

Lingchi Kong1,2,3, Xin Gao4, Yun Qian1,2,3✉, Wei Sun4✉, Zhengwei You4✉, Cunyi Fan1,2,3✉

1. Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
2. Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 200233, China.
3. Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
4. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Belt and Road Joint Laboratory of Advanced Fiber and Low-dimension Materials, College of Materials Science and Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai, 201620, China.

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Kong L, Gao X, Qian Y, Sun W, You Z, Fan C. Biomechanical microenvironment in peripheral nerve regeneration: from pathophysiological understanding to tissue engineering development. Theranostics 2022; 12(11):4993-5014. doi:10.7150/thno.74571. Available from

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Graphic abstract

Peripheral nerve injury (PNI) caused by trauma, chronic disease and other factors may lead to partial or complete loss of sensory, motor and autonomic functions, as well as neuropathic pain. Biological activities are always accompanied by mechanical stimulation, and biomechanical microenvironmental homeostasis plays a complicated role in tissue repair and regeneration. Recent studies have focused on the effects of biomechanical microenvironment on peripheral nervous system development and function maintenance, as well as neural regrowth following PNI. For example, biomechanical factors-induced cluster gene expression changes contribute to formation of peripheral nerve structure and maintenance of physiological function. In addition, extracellular matrix and cell responses to biomechanical microenvironment alterations after PNI directly trigger a series of cascades for the well-organized peripheral nerve regeneration (PNR) process, where cell adhesion molecules, cytoskeletons and mechanically gated ion channels serve as mechanosensitive units, mechanical effector including focal adhesion kinase (FAK) and yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) as mechanotransduction elements. With the rapid development of tissue engineering techniques, a substantial number of PNR strategies such as aligned nerve guidance conduits, three-dimensional topological designs and piezoelectric scaffolds emerge expected to improve the neural biomechanical microenvironment in case of PNI. These tissue engineering nerve grafts display optimized mechanical properties and outstanding mechanomodulatory effects, but a few bottlenecks restrict their application scenes. In this review, the current understanding in biomechanical microenvironment homeostasis associated with peripheral nerve function and PNR is integrated, where we proposed the importance of balances of mechanosensitive elements, cytoskeletal structures, mechanotransduction cascades, and extracellular matrix components; a wide variety of promising tissue engineering strategies based on biomechanical modulation are introduced with some suggestions and prospects for future directions.

Keywords: Peripheral nerve injury, Peripheral nerve regeneration, Biomechanical phenomena, Mechanotransduction, Biomaterials, Tissue engineering