Alireza Maboudi, Morvarid Taherkhani, Mostafa Asadi, Fakhri Haghi, Narges Forouzideh, Ali Zamani
Hybrid bioactive materials are increasingly explored as antibiotic-sparing alternatives for wound-associated applications; however, their biological performance is often governed by material-mediated exposure rather than the intrinsic potency of the incorporated agents. In this proof-of-concept study, thermally crosslinked electrospun poly vinyl alcohol/hyaluronic acid (PVA/HA) nanofibers were investigated as a diffusion-governed composite platform for the co-incorporation of curcumin and an unfractionated Micrococcus luteus -derived postbiotic. The study focused on elucidating structure-hydration-diffusion relationships that constrain local antibacterial exposure in hybrid phytochemical–postbiotic systems. Uniform, bead-free nanofibers with an average diameter of 245 ± 19 nm were obtained following electrospinning and thermal treatment, exhibiting high swelling capacity, gradual degradation, and favorable hemocompatibility. In vitro curcumin release displayed a biphasic profile over 24 h and was best described by the Korsmeyer-Peppas model (n = 0.213, R 2 = 0.981), indicating predominantly Fickian diffusion through the hydrated polymer network. While the M. luteus postbiotic demonstrated concentration-dependent antibacterial activity in solution, its incorporation within the PVA/HA nanofiber matrix resulted in selective inhibition of Pseudomonas aeruginosa and negligible activity against Staphylococcus aureus . The Gram-dependent antibacterial outcome highlights an exposure-threshold mismatch imposed by diffusion-limited transport and matrix–metabolite interactions, rather than a lack of intrinsic bioactivity. Rather than presenting an optimized therapeutic dressing, this work provides a sound materials-focused evaluation of how electrospun composite design governs diffusion-controlled exposure and biological response, offering mechanistic insight to inform the rational development of hybrid antibiotic-free delivery systems.