2. Academic Validation
  3. LDH nanoparticles-doped cellulose nanofiber scaffolds with aligned microchannels direct high-efficiency neural regeneration and organized neural circuit remodeling through RhoA/Rock/Myosin II pathway

LDH nanoparticles-doped cellulose nanofiber scaffolds with aligned microchannels direct high-efficiency neural regeneration and organized neural circuit remodeling through RhoA/Rock/Myosin II pathway

  • Biomaterials. 2025 Mar:314:122873. doi: 10.1016/j.biomaterials.2024.122873.
Xuening Pang 1,  Tongling Zhang 2,  Jiazheng Li 1,  Liqun Yu 1,  Zhibo Liu 3,  Yuchen Liu 3,  Li Li 4,  Liming Cheng 5,  Rongrong Zhu 6
Affiliations

Affiliations

  • 1 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China; Frontier Science Center for Stem Cell Research, Clinical Center for Brain and Spinal Cord Research, Tongji University, Shanghai, 200065, China.
  • 2 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.
  • 3 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China.
  • 4 Department of Respiratory Disease, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China; Department of Respiratory Disease, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 201999, China. Electronic address: yefan718@163.com.
  • 5 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China. Electronic address: limingcheng@tongji.edu.cn.
  • 6 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200065, China; Frontier Science Center for Stem Cell Research, Clinical Center for Brain and Spinal Cord Research, Tongji University, Shanghai, 200065, China. Electronic address: rrzhu@tongji.edu.cn.
PMID: 39369670 DOI: 10.1016/j.biomaterials.2024.122873
Abstract

Spinal cord injury (SCI) triggers interconnected malignant pathological cascades culminating in structural abnormalities and composition changes of neural tissues and impairs spinal cord tissue function. Cellulose nanofibers (CNF) have considerable potential in mimicking tissue microstructure for nerve regeneration, but the effectiveness of CNF in repairing SCI remains poorly understood. In this study, we designed a Mg-Fe layered double hydroxide (LDH)-doped cellulose nanofiber (CNF) scaffold with aligned intact microchannels and homogeneously distributed pores (CNF-LDH), loaded with retinoic acid and sonic Hedgehog (CNF-LDH-RS) for neuroregeneration. The aligned microchannel structure and chemical cues in the scaffold were designed further to enhance the differentiation of neural stem cells towards neurons and promote axon growth while inhibiting differentiation to astrocytes. Transplanting the scaffolds into a completely transected SCI mice model dramatically improved behavioral and electrophysiological outcomes underpinned by robust neuronal regeneration, significant axonal growth and orderly neural circuit remodeling. RNA-seq analysis revealed the pivotal roles of the RhoA/ROCK/Myosin II pathway and neuroactive ligand-receptor interaction pathway in SCI repair by CNF-LDH-RS. Particularly, Myosin II emerged as a key gene for functional recovery, and its effect on negative regulation of axon growth was suppressed by the scaffolds, resulting in a distinctly oriented growth of the axons along the microchannel structure. The results indicate that CNF-LDH scaffolds rationally combined with physical and biochemical cues create promising tissue-engineered substrates to facilitate the repair of spinal cord injury.

Keywords

Aligned microchannels; Cellulose nanofiber; Myosin II; Nerve regeneration; Spinal cord injury.

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