Enhancement of spinal cord injury repair in rats using photo‐crosslinked GelMA hydrogel combined with mitochondrial transplantation

Abstract Acute spinal cord injury (SCI) induces mitochondrial oxidative stress, cellular bioenergetic crises, impaired protein degradation, and subsequent degeneration, resulting in increased neuronal vulnerability. Transplantation of exogenous mitochondria to the injury site mitigates cellular energy crises and counteracts neurodegeneration; however, the limited efficacy of mitochondrial transplantation alone constrains its therapeutic potential. In this study, we established a right‐sided spinal cord hemisection model at the T10 thoracic segment in rats and transplanted a methacrylate‐based gelatin (GelMA) hydrogel containing active mitochondria at the injury site to assess its therapeutic effects and underlying mechanisms. Our findings indicate that GelMA hydrogel combined with mitochondrial transplantation provides superior therapeutic benefits for SCI compared to mitochondrial transplantation alone. GelMA hydrogel enables sustained mitochondrial release at the injury site, supplying energy, upregulating NF200 expression, and promoting axonal regeneration. Additionally, it enhances M2 macrophage accumulation and improves the local inflammatory microenvironment. The structural framework of GelMA hydrogel further supports axonal regeneration. Footprint gait analysis and Basso, Beattie, and Bresnahan (BBB) motor scoring demonstrated that GelMA hydrogel combined with mitochondrial transplantation significantly improves motor function in the right hind limb of rats with SCI. Consequently, GelMA hydrogel combined with mitochondrial transplantation offers a viable and promising approach for treating spinal cord injury.