Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (3): 1222-1235.doi: 10.4103/NRR.NRR-D-24-00302

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Porcine decellularized nerve matrix hydrogel attenuates neuroinflammation after peripheral nerve injury by inhibiting the TLR4/MyD88/NF-κB axis

Rui Li1, 2, Jianquan Liu1 , Liuxun Li1 , Guotian Luo1 , Xinrong Yuan1 , Shichao Shen1 , Yongpeng Shi1 , Jianlong Wu1 , Bin Yan1, *, Lei Yang1, *   

  1. 1 Orthopaedics/Department of Spine Surgery, Department of Pharmacy, Shenzhen Second People’s Hospital (the First Affiliated Hospital, Shenzhen University), Medical Innovation Technology Transformation Center of Shenzhen Second People’s Hospital, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong Province, China;  2 State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong Province, China
  • Online:2026-03-15 Published:2025-07-05
  • Contact: Bin Yan, MD, yanbinzhiyou@163.com; Lei Yang, MD, yangl@email.szu.edu.cn.
  • Supported by:
    This study was supported by the Shenzhen Hong Kong Joint Funding Project, No. SGDX20230116093645007 (to LY); the Shenzhen Science and Technology Innovation Committee International Cooperation Project, No. GJHZ20200731095608025 (to LY); Shenzhen Development and Reform Commission’s Intelligent Diagnosis, Treatment and Prevention of Adolescent Spinal Health Public Service Platform, No. S2002Q84500835 (to LY); Shenzhen Medical Research Fund, No. B2303005 (to LY); Team-based Medical Science Research Program, No. 2024YZZ02 (to LY); Zhejiang Provincial Natural Science Foundation of China, No. LWQ20H170001 (to RL); Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission, No. JCYJ20210324103010029 (to BY); Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project, Nos. 2023yjlcyj029 (to BY), 2023yjlcyj021 (to LL); Guangdong Basic and Applied Basic Research Foundation, No. 2022A1515110679 (to LL); and China Postdoctoral Science Foundation, No. 2022M722203 (to GL).

Abstract: Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge. Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity, highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury; however, its role in modulating neuroinflammation post–peripheral nerve injury remains unknown. Here, we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms. Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel, we evaluated structural and functional recovery, macrophage phenotype alteration, specific cytokine expression, and changes in related signaling molecules in vivo. Similar parameters were evaluated in vitro using monocyte/ macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel–coated plates in complete medium. These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages. Additionally, porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro. Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway, providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.

Key words: anti-inflammatory reaction, macrophage polarization, neuroinflammation, peripheral nerve injury, porcine decellularized nerve matrix hydrogel