Electrospun Polymeric Nanofibers Incorporating Brazilian Red Propolis Extract for Wound Dressing Applications

Background/Objectives: Chronic wounds remain difficult to manage because persistent inflammation, microbial colonization, and excess exudate require dressings that combine structural integrity, bioactivity, antimicrobial performance, and cytocompatibility. This study aimed to develop electrospun nanofibrous mats based on gelatin, poly(vinyl alcohol) (PVA), and poly(ε-caprolactone) (PCL), with and without Brazilian red propolis extract (BRPE), and to evaluate how extract incorporation affects solution properties, fiber morphology, fluid interaction, antimicrobial activity, and cytocompatibility. Methods: BRPE was characterized in terms of solid content, total phenolic content, antioxidant activity, and HPLC-DAD marker profile. Polymeric solutions were evaluated for electrical conductivity and rheological behavior and then processed by electrospinning under fixed conditions. The resulting mats were characterized by scanning electron microscopy, surface porosity, FTIR, and HPLC-DAD. Their performance was further assessed by swelling-associated degradation in simulated wound fluids, agar diffusion antimicrobial assays, and MTT cytocompatibility assays using HaCaT cells. Results: BRPE showed a solid content of 3.88%, a total phenolic content of 8.79 ± 0.21 mg pyrogallol equivalents g^-1 extract, and an antioxidant activity of 75.32 ± 9.80 mg Trolox equivalents g^-1 extract. HPLC-DAD confirmed preservation of the BRPE chromatographic fingerprint after electrospinning, with high retention of marker peaks associated with liquiritigenin and a formononetin-related signal. Solution conductivity varied with polymer composition and BRPE incorporation; for example, the PVA:gelatin:PCL formulation A4/A4.1 at 70:20:10 decreased from 919.6 to 539.6 µS cm^-1 after BRPE loading. Electrospinning produced continuous, defect-free fibers with mean diameters ranging from 94 to 224 nm and surface porosity between 9.8 and 10.6%. Most hydrophilic systems showed rapid fluid interaction but limited wet-state structural stability; among the quantified formulations, A5 showed the lowest mass loss, indicating better structural preservation under simulated wound conditions. BRPE-loaded mats showed microorganism-dependent antimicrobial activity, with the strongest inhibition against Staphylococcus epidermidis and Klebsiella pneumoniae and no activity against Pseudomonas aeruginosa. Free BRPE showed marked cytotoxicity, whereas selected electrospun formulations, especially A1.1 and A3.1, improved HaCaT cell viability. Conclusions: Electrospinning was an effective strategy for incorporating BRPE into polymeric nanofibers and modulating the physicochemical and biological performance of the resulting mats. These findings support the potential of these materials as multifunctional wound-dressing platforms, although further optimization is needed to improve wet-state structural stability, mechanical performance, and bioactive release.