Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (12): 3591-3605.

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A vascular endothelial growth factor–loaded chitosanhyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke

Zhijian Zheng1, 2, 3, 4, #, Xiaohui Lin1, 2, 3, 4, #, Zijun Zhao1, 2, 3, 4, #, Qiang Lin1, 2, 3, 4, Ji Liu1, 2, 3, 4, Manli Chen1, 2, 3, 4, Wenwen Wu1, 2, 3, 4, Zhiyun Wu1, 2, 3, 4, Nan Liu1, 2, 3, 4, *, Hongbin Chen1, 2, 3, 4, *   

  1. 1 Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China;  2 Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China;  3 Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian Province, China;  4 Institute of Clinical Neurology, Fujian Medical University, Fuzhou, Fujian Province, China
  • Online:2025-12-15 Published:2025-03-17
  • Contact: Hongbin Chen, MD, hbchen0127@fjmu.edu.cn; Nan Liu, xieheliunan@163.com.
  • Supported by:
    This study was supported by a grant from the Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital, No. 2022XH026 (to HC); Joint Funds for the Innovation of Science and Technology in Fujian Province, No. 2019Y9058 (to XL); the Natural Science Foundation of Fujian Province, No. 2020J011017 (to XL).

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Abstract: Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemiareperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

Key words: adipose-derived stem cells, chitosan, hyaluronic acid, hydrogel, ischemia-reperfusion, oxygen-glucose deprivation/reoxygenation, stroke, transient middle cerebral artery occlusion, transplantation, vascular endothelial growth factor