In Situ Electrospinning of Mesenchymal Stem Cell-Laden Gelatin-Dopamine Fibers for Accelerated Diabetic Wound Healing

Diabetic wound healing remains a critical clinical challenge due to impaired regeneration and chronic inflammation. In this study, we explore the potential of in situ electrospinning of live human umbilical cord mesenchymal stem cells (HUCMSCs) to enhance diabetic wound healing. For this purpose, HUCMSCs were combined with a gelatin-dopamine (Gel-DA) aqueous solution to serve as a "bioink" for cell electrospinning. The Gel-DA biomaterial was synthesized by grafting dopamine onto fish gelatin, which exhibits exceptional biocompatibility and potent antioxidant properties, crucial for diabetic wound microenvironments. At an optimized voltage of 13 kV, we achieved direct deposition of viable HUCMSC-laden Gel-DA fibers onto wounds, maintaining >90% cell viability and metabolic activity. In vivo studies in diabetic mice demonstrated that in situ electrospun MSCs/Gel-DA constructs significantly accelerated wound closure, alleviated inflammation, and promoted collagen deposition and angiogenesis (with a 2.5-fold increase in CD31+ vessels, <i>p</i> < 0.0001). Histological analysis revealed enhanced appendage regeneration and reduced scarring in treated wounds. This work establishes in situ cell electrospinning as an appealing platform for synergistic stem cell and biomaterial delivery, offering a promising therapeutic strategy for diabetic wound management.