Chronic wounds present a major clinical challenge due to impaired healing and prolonged inflammation. This present study aimed to develop and assess a platelet-rich plasma (PRP)-loaded decellularized skin-derived matrix scaffold (SDMP) for enhanced wound healing. A total of 40 male Sprague-Dawley rats were randomly planned to four groups (n = 10 per group): untreated control, PRP, decellularized skin-derived matrix (SDM), and PRP-loaded SDM (SDMP). Full-thickness excisional wounds were created on the dorsal surface of each animal and treatments were applied accordingly. Tissue sampling was performed at two time points-day 7 and day 14 post-injury-with five animals per group euthanized at each time point. Histological evaluations included assessment of newly formed epidermal length, dermal thickness, and collagen density. Biomechanical properties of the regenerated skin were analyzed on day 14 using tensile strength testing. In addition, concentrations of key regenerative (TGF-β1, VEGF) and pro-inflammatory (TNF-α, IL-1β) cytokines in wound tissues were quantified via ELISA. The SDMP-treated group showed significantly enhanced wound closure, improved re-epithelialization and dermal regeneration, greater collagen deposition, and superior tensile strength compared with other groups (p < 0.05). Moreover, cytokine analysis revealed a favorable shift in the wound microenvironment characterized by elevated growth factors and reduced inflammatory mediators (p < 0.05). In conclusion, the PRP-loaded SDMs provides a bioactive and biocompatible platform that significantly improves full-thickness skin diabetic wound healing. This approach holds promise for future translational applications in regenerative medicine.
