Accurate Delivery of Mesenchymal Stem Cell Spheroids With Platelet‐Rich Fibrin Shield: Enhancing Survival and Repair Functions of Sp‐MSCs in Diabetic Wound Healing

Diabetic wound is a significant clinical challenge, and stem cell therapy has shown great potential. This study explores the role of mesenchymal stem cell (MSC) spheroids (Sp-MSCs) in healing diabetic wounds and the use of autologous plasma-rich platelet fibrin (PRF) as a scaffold for Sp-MSCs. Through activation of the coagulation system, PRF offers a protective fibrin shield for Sp-MSCs to promote the rapid recovery migration and proliferation of MSCs while maintaining the activity of Sp-MSCs in an inflammatory overload environment by activating the related genes of Integrin-β1-vascular endothelial growth factor (VEGF), and Wnt/β-catenin pathways. The inclusion of Sp-MSCs accelerates the gelation of PRF and results in improved mechanical strength. Additionally, PRF enhances the repair function of Sp-MSCs, creating a favorable microenvironment for angiogenesis. In the wound model of diabetic mice, the combination of PRF with Sp-MSCs accelerates wound healing. Results show that this combination significantly promotes wound repair and regulates the immune microenvironment. The study suggests that PRF is a promising bio-derived scaffold for stem cell applications in diabetic wounds, offering new directions for stem cell therapy and biomimetic scaffold material development.