Local release of fibroblast growth factor 21 and cannabidiol promoting spinal cord nerve injury repair through activation of cannabinoid receptor 2

  • Biomaterials. 2026 Feb:325:123609. doi: 10.1016/j.biomaterials.2025.123609.
Zhao Zhang  1 ,  Zhengquan Wang  2 ,  Zhihao Shen  3 ,  Yangbo Zhou  1 ,  Cheng Zhou  1 ,  Min Chen  4 ,  Minghao Jiang  4 ,  Junyu Zhuang  4 ,  Jiahui Song  4 ,  Xiangyang Wang  4 ,  Shixuan Chen  5 ,  Jian Xiao  6 ,  Sipin Zhu  7
Affiliations
  • 1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China; Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of the Chinese Academy of Sciences, Wenzhou, 325000, Zhejiang, China.
  • 2. Department of Emergency Medicine, The Affiliated Yangming Hospital of Ningbo University, Ningbo, Zhejiang, China.
  • 3. Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of the Chinese Academy of Sciences, Wenzhou, 325000, Zhejiang, China; Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
  • 4. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
  • 5. Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of the Chinese Academy of Sciences, Wenzhou, 325000, Zhejiang, China. Electronic address: [email protected].
  • 6. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China; Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. Electronic address: [email protected].
  • 7. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address: [email protected].
PMID: 40782447 DOI: 10.1016/j.biomaterials.2025.123609
Abstract

Spinal cord injury (SCI) is a debilitating condition that leads to severe motor and sensory dysfunction, largely due to inflammation, neuronal damage, and disrupted neural circuits. In this study, we developed an injectable hydrogel (C/F/Gel) co-loaded with Fibroblast Growth Factor 21 (FGF21) and cannabidiol micelles (CBDm) to enhance SCI repair. The hydrogel, composed of PF127 and α-cyclodextrin (α-CD), provides sustained drug release and improves drug stability at the injury site. Our findings demonstrate that C/F/Gel effectively modulates the inflammatory microenvironment by promoting microglial polarization toward the anti-inflammatory M2 phenotype via Cannabinoid Receptor 2 (CB2R) activation. Additionally, it regulates the balance between excitatory and inhibitory neurons, and significantly improves motor function in SCI mice. Behavioral assessments, histological analysis, and molecular studies confirmed the superior therapeutic efficacy of C/F/Gel compared to single-agent treatments. These results highlight C/F/Gel as a promising biomaterial-based strategy for SCI repair, offering a synergistic approach that integrates inflammation modulation, neuroprotection, and functional recovery.

Keywords
Cannabidiol; Fibroblast growth factor 21; Inflammation modulation; Neuroprotection; Spinal cord injury.
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