2. Academic Validation
  3. Highly Bioadaptable Hybrid Conduits with Spatially Bidirectional Structure for Precision Nerve Fiber Regeneration via Gene Therapy

Highly Bioadaptable Hybrid Conduits with Spatially Bidirectional Structure for Precision Nerve Fiber Regeneration via Gene Therapy

  • Adv Sci (Weinh). 2024 Mar 14:e2309306. doi: 10.1002/advs.202309306.
Renliang Zhao 1 2,  Xiangtian Deng 1 2,  Jizhao Dong 3,  Chen Liang 3,  Xiaozhong Yang 1 2,  Yunfeng Tang 4,  Juan Du 3,  Zilu Ge 1 2,  Dong Wang 1 2,  Yifan Shen 5,  Lianghua Jiang 6,  Wei Lin 7,  Tonghe Zhu 3,  Guanglin Wang 1 2
Affiliations

Affiliations

  • 1 Orthopedics Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.
  • 2 Trauma Medical Center, Department of Orthopedics Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 3 Multidisciplinary Centre for Advanced Materials, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Rd., Shanghai, 201620, P. R. China.
  • 4 Head & Neck Oncology Ward, Cancer Center, West China Hospital, Cancer Center, Sichuan University, Chengdu, 610041, P. R. China.
  • 5 Spine Lab, Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • 6 Department of Orthopedic Trauma, The First People's Hospital of Kunshan affiliated with Jiangsu University, Suzhou, Jiangsu, 215300, P. R. China.
  • 7 Department of Gynecology, West China Second Hospital, Sichuan University, Chengdu, 610041, P. R. China.
PMID: 38483934 DOI: 10.1002/advs.202309306
Abstract

Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual-delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor β (TGF-β) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering.

Keywords

Wallerian degeneration; genetic therapy; nerve conduits; neuroautonomous selectivity; neuroplasticity.

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