Electrospun Hyaluronic Acid/Polyvinyl Alcohol Nanofibers Encapsulating Defactinib as Bioactive Dressings for Burn Wound Therapy

Chronic burn wounds remain a significant clinical challenge due to prolonged inflammation, delayed tissue regeneration, and limited effectiveness of current topical therapies. In this study, electrospun hyaluronic acid/poly(vinyl alcohol) (HA/PVA) nanofiber scaffolds loaded with Defactinib, a focal adhesion kinase inhibitor, were developed to promote burn wound healing through localized drug delivery. Optimized electrospinning conditions produced uniform, bead-free nanofibers with stable amorphous drug dispersion, as confirmed by SEM, TEM, XRD, and DSC analyses. The Defactinib-loaded nanofibers exhibited (DFT-NF) high drug entrapment efficiency, good hydrophilicity, and a biphasic release profile characterized by an initial burst followed by sustained release over 24 h. In a rat burn wound model, treatment with Defactinib-loaded nanofibers significantly accelerated wound closure compared with untreated and standard-treated groups. Non-invasive photoacoustic imaging enabled real-time monitoring of wound healing, revealing increased vascularity and improved tissue oxygen saturation in treated wounds by Day 21, indicative of enhanced vascular recovery. Histological evaluation further confirmed improved re-epithelialization, reduced inflammatory infiltration, and well-organized collagen deposition. Consistent with these findings, RT-PCR analysis showed marked suppression of key pro-inflammatory mediators (NF-κB, IL-1β, TNF-α, and IL-6) in the DFT-NF group, highlighting its potent anti-inflammatory activity. Overall, this study demonstrates that Defactinib-loaded HA/PVA nanofiber scaffolds, combined with imaging-based functional assessment, represent a promising and clinically relevant platform for advanced burn wound management.