Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Delayed and nonhealing of diabetic wounds impose substantial economic burdens and physical pain on patients. Mesenchymal stem cells (MSCs) promote diabetic wound healing. Particularly, when MSCs aggregate into multicellular spheroids, their therapeutic effect is enhanced. However, traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids, resulting in inefficiencies and inconveniences in MSC spheroid therapy. In this study, a three-dimensional porous nanofibrous dressing (NFD) is prepared using a combination of electrospinning and homogeneous freeze-drying. Using thermal crosslinking, the NFD not only achieves satisfactory elasticity, but also maintains notable cytocompatibility. Through the design of its structure and chemical composition, the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes, serving as MSC spheroid delivery systems for diabetic wound sites. Most importantly, MSC spheroids cultured on the NFD exhibits improved secretion of vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, thereby accelerating diabetic wound healing. The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.