Electrospun silk sericin–poly(lactic acid) coaxial nanofiber scaffold for esmolol and ferulic acid co-delivery in expedited diabetic wound healing

Diabetic foot ulcers (DFUs) are chronic, infection-prone wounds that heal poorly due to impaired angiogenesis, persistent inflammation, and elevated oxidative stress, creating a substantial clinical and economic burden and highlighting the need for advanced extracellular matrix-mimicking dressings. Therefore, we have developed a ferulic acid (FA)-esmolol (ESM)-loaded coaxial nanofibrous (NFs) scaffold using silk sericin (SS) as the shell and poly(lactic acid) (PLA) as the core via electrospinning for DFU management. The optimized scaffold showed a uniform, bead-free morphology with increased fiber diameter (370 ± 95 nm) compared to blank NFs (201 ± 52 nm) and a confirmed core-shell architecture. The FA-ESM NFs demonstrated high porosity (81.04 ± 4.39%) and an optimal water vapor transmission rate (WVTR) (2077 g/m2/day), supporting a moist wound environment. Water retention (409.39 ± 12.41%) and controlled biodegradation (~98% over 21 days) indicated excellent exudate handling and sustained structural integrity. Mechanical analysis showed suitable tensile strength (1.20 MPa) and elongation (112.80%). Drug release followed the Korsmeyer-Peppas model (R2 ≈ 0.975/0.9811; n = 0.699/0.883), indicating anomalous to case II transport. The scaffold exhibited significant antioxidant activity, >80% cell viability, and hemocompatibility. It significantly enhanced cell migration within 48 h and modulated biomarkers (↓MMP-9, ↓TNF-α, ↑VEGF; p < 0.01). Strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, along with significantly accelerated wound closure in diabetic models within 16 days (p < 0.0001), further validates its therapeutic efficacy. Overall, the scaffold demonstrates promising anti-inflammatory, antioxidant, and pro-angiogenic properties and potentially effective dressing for DFU management.