Decellularized dermal scaffold biofunctionalized with quercetin nanoparticles enhances angiogenesis and attenuates inflammation in type 2 diabetic wounds.

Chronic diabetic wounds are characterized by excessive inflammation, impaired angiogenesis, and oxidative stress, leading to delayed tissue regeneration and poor healing outcomes. In this study, a biofunctionalized decellularized dermal scaffold incorporating quercetin nanoparticles (SCS-QNP) was developed to enhance the biological performance of the scaffold for type 2 diabetic wound repair. The scaffold was fabricated and systematically characterized in terms of its structural integrity and physicochemical properties. Its regenerative potential was evaluated in a streptozotocin-induced diabetic rat wound model. Wound healing efficacy was assessed through macroscopic wound closure, histological analysis, mechanical properties, and the expression of key regenerative growth factors, inflammatory cytokines, and oxidative stress markers. The SCS-QNP scaffold significantly accelerated wound closure compared with untreated controls and non-functionalized scaffolds. Histological findings demonstrated enhanced fibroblast proliferation, increased vascularization, reduced inflammatory cell infiltration, increased mechanical properties, and improved collagen organization. Furthermore, treatment with the SCS-QNP scaffold resulted in upregulation of pro-regenerative growth factors (TGF-β1, bFGF, and VEGF), downregulation of inflammatory cytokines (IL-1β and TNF-α), and restoration of antioxidant balance within the wound microenvironment. These findings indicate that biofunctionalization of a decellularized dermal scaffold with quercetin nanoparticles effectively improves its regenerative performance, highlighting its potential as a multifunctional biomaterial for the treatment of chronic diabetic wounds.