Engineered dual-layered polyvinyl alcohol-alginate wound dressings incorporating antimicrobial and pro-healing functions.

The management of cutaneous wound remains a significant clinical challenge, necessitating advanced dressings that can simultaneously combat infection, modulate inflammation, and actively promote tissue regeneration. To address this, we engineered a novel dual-layered dressing consisting of an electrospun polyvinyl alcohol (PVA) nanofibrous layer and an alginate hydrogel layer. The PVA layer was functionalized with RGD-displaying M13 bacteriophages and the antimicrobial peptide SAAP-148. The alginate hydrogel was loaded with zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, either alone or loaded with curcumin (cur@ZIF-8). Structural characterization confirmed uniform nanoparticle morphology and a high curcumin loading efficiency of 72.78%. The cur@ZIF-8 system exhibited a smart, pH-responsive release, with 88.19% of curcumin released at the acidic pH of 5.5 compared to only 23.70% at pH 7.4. The scaffolds demonstrated optimal physical and mechanical properties, tunable swelling, and broad-spectrum antimicrobial activity. SAAP-148 peptide exhibited potent antimicrobial activity against Staphylococcus aureus (MIC: 4 μg/mL, MBC: 8 μg/mL), Escherichia coli (MIC: 1 μg/mL, MBC: 2 μg/mL), and Candida albicans (MIC: 2 μg/mL, MFC: 4 μg/mL), that demonstrating cidal effects at low concentrations, excellent hemocompatibility (2-4% hemolysis), and enhanced cell migration. In vivo studies revealed accelerated wound healing, with the complete dual-layered dressing promoting full re-epithelialization, organized collagen deposition, and neovascularization within 21 days. This enhanced healing was attributed to a synergistic combination of Zn2+-mediated immunomodulation, curcumin's antioxidant activity, phage-mediated healing effects and peptide antimicrobial action.