2. Academic Validation
  3. Phase-adapted metal ion supply for spinal cord repair with a Mg-Zn incorporated chimeric microsphere

Phase-adapted metal ion supply for spinal cord repair with a Mg-Zn incorporated chimeric microsphere

  • Biomaterials. 2025 Mar 11:320:123253. doi: 10.1016/j.biomaterials.2025.123253.
Xiangyu Liu 1,  Biao Ma 2,  Sihan Hu 3,  Dandan Li 3,  Chun Pan 3,  Zhuobin Xu 3,  Hao Chen 4,  Yongxiang Wang 5,  Huihui Wang 6
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Department of Orthopedics, Affiliated Hospital of Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, China.
  • 2 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Department of Orthopedics, Affiliated Hospital of Yangzhou University, Yangzhou, China.
  • 3 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
  • 4 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Department of Orthopedics, Affiliated Hospital of Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, China. Electronic address: hchen2020@yzu.edu.cn.
  • 5 Department of Orthopaedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China; Department of Orthopaedics, Northern Jiangsu People's Hospital, Yangzhou, China. Electronic address: wyx918spine@yzu.edu.cn.
  • 6 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, China. Electronic address: wanghh56@yzu.edu.cn.
PMID: 40107180 DOI: 10.1016/j.biomaterials.2025.123253
Abstract

Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg2+-crosslinked methacrylate gelatin as the "shell" and Zn2+-loaded poly (lactic-co-glycolic acid) (PLGA) as the "core" was designed. The chimeric microspheres allow continuous delivery of Mg2+ or Zn2+ at the exact required phase in SCI pathological process. Early release of Mg2+ reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn2+ at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.

Keywords

Core-shell structure; Injectable chimeric microspheres; Metal ions; Spinal cord injury.

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