PDGF-loaded eugenol-impregnated biocompatible nanofibrous scaffolds for enhanced diabetic wound healing and vascularization

Abstract

Diabetic foot ulcers (DFUs) represent a major clinical challenge due to their high infection risk, long-term severe infections and limb amputations. In the current study, multifunctional platelet-derived growth factor (PDGF)-impregnated eugenol microemulsion (EuME)-based silver nanocomposites (PDGF/EuME–AgNPs/CSNs) embedded within a PVA/chitosan base matrix have been fabricated. The synergistic effects of PVA/chitosan accelerate wound closure while exhibiting broad-spectrum antimicrobial and anti-inflammatory properties. The polymeric matrix facilitates proliferation and migration of keratinocytes and fibroblasts, promoting tissue regeneration. The electrospun nanofibrous mats exhibited homogenous surface morphology with a uniform pore size distribution of 100–250 nm, a water uptake and absorption percentage of 96%, an optimal porosity of 94.7, a mass loss capacity of 60.36%, a water contact angle of 68° and a tensile strength of 1.2 MPa, facilitating mechanical flexibility and providing an optimal moist wound environment. The PDGF/EuME–AgNPs/CSNs scaffolds demonstrated 95% antimicrobial inhibitory activity against S. aureus and P. aeruginosa. In vivo studies showed significantly accelerated wound contraction by the 9th day, achieving maintenance of 98% glycemic levels when compared to control groups, which exhibited 20% wound contraction (p < 0.01). The nanofibers reduce inflammation and promote fibroblast production, collagen deposition, and fibrin regeneration. Increased levels of CD-31, IL-1, and TGF-β confirmed improved re-epithelialization, vascularization, and skin regeneration. The findings suggested that PDGF/EuME–AgNPs/CSNs accelerate diabetic wound healing, enable sustained growth factor delivery, and promote vascularization and re-epithelialization, demonstrating their potential in improving DFU treatment outcomes.