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

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

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: chensx@ucas.ac.cn.
  • 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: xfxj2000@126.com.
  • 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: sipinzhu@163.com.
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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