Granular Porous\nNanofibrous Microspheres Enhance Cellular\nInfiltration for Diabetic Wound Healing

Diabetic foot ulcers (DFUs) are a significant challenge\nin the\nclinical care of diabetic patients, often necessitating limb amputation\nand compromising the quality of life and life expectancy of this cohort.\nMinimally invasive therapies, such as modular scaffolds, are at the\nforefront of current DFU treatment, offering an efficient approach\nfor administering therapeutics that accelerate tissue repair and regeneration.\nIn this study, we report a facile method for fabricating granular\nnanofibrous microspheres (NMs) with predesigned structures and porosities.\nThe proposed technology combines electrospinning and electrospraying\nto develop a therapeutic option for DFUs. Specifically, porous NMs\nwere constructed using electrospun poly(lactic-<i>co</i>-glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin\ncross-linking. These NMs demonstrated enhanced cell adhesion to human\ndermal fibroblasts (HDF) during an <i>in vitro</i> cytocompatibility\nassessment. Notably, porous NMs displayed superior performance owing\nto their interconnected pores compared to nonporous NMs. Cell-laden\nNMs demonstrated higher Young’s modulus values than NMs without\nloaded cells, suggesting improved material resiliency attributed to\nthe reinforcement of cells and their secreted extracellular matrix.\nDynamic injection studies on cell-laden NMs further elucidated their\ncapacity to safeguard loaded cells under pressure. In addition, porous\nNMs promoted host cell infiltration, neovascularization, and re-epithelialization\nin a diabetic mouse wound model, signifying their effectiveness in\nhealing diabetic wounds. Taken together, porous NMs hold significant\npotential as minimally invasive, injectable treatments that effectively\npromote tissue integration and regeneration.