Layer-by-layer electrospun PCL/PVA mats loaded with nisin Z for enhanced diabetic foot ulcer treatment

Diabetic foot ulcers (DFUs) represent a significant clinical challenge due to impaired healing and high susceptibility to infections, underscoring the urgent need for multifunctional wound dressings. This study explores the potential of multilayered electrospun mats composed of polycaprolactone (PCL) and poly(vinyl alcohol) (PVA) engineered by a layer-by-layer (LbL) electrospun-based deposition, and functionalized with the antimicrobial peptide (AMP) nisin Z. Three LbL configurations (PCL/PVA, PCL/PVA/PCL, and PCL/PVA/PCL/PVA) were produced and characterized in terms of physicochemical, mechanical and biological performance. The mats exhibited tensile strengths of 0.9-2.7 MPa, swelling degree < 90 % and ≈ 20 % degradation after 7 and 28 days under physiological-like environments, respectively, while maintaining air permeability between 0.5 and 1.3 mL/cm²/s. Biocompatibility assays using HaCaT keratinocytes demonstrated excellent cytocompatibility, with metabolic activity exceeding 93 %, cell growth above 87 %, and enhanced cell migration leading to wound closure within 16 h. The incorporation of nisin Z provided significant antimicrobial activity against Gram-positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, achieving up to 100 % bacterial inhibition within 24 h, and reducing biofilm formation by more than 50 %. Among the tested mats, the PCL/PVA/PCL configuration revealed the most promising features. Overall, these findings highlight the potential of multilayer electrospun mats as bioactive wound dressings for DFUs, offering a multi-action strategy for improved wound healing.