Hyaluronic acid electrospun nanofiber patch for accelerated chronic recurrent oral aphthous ulcers

In this study, we electrospun a bio-resorbable nanofiber patch from dopamine-crosslinked hyaluronic acid (HA) that combines mucoadhesion, antibacterial activity and pro-healing functions. Sodium periodate oxidation of HA under acidic conditions generated aldehyde-rich oxidized HA (OHA) that was subsequently conjugated with dopamine hydrochloride through dual aldehyde/carboxyl reactions, yielding dopamine-OHA (DHA) with 12.8% substitution. Optimized electrospinning (8% w/w DHA, 5:5 spinning-aid ratio, 18 kV, 1.2 mL h^-1, 20 cm gap) produced uniform nanofibers (162 ± 3.32 nm) that were post-crosslinked with ε-poly-l-lysine (EPL) to enhance wet strength, slow dissolution and introduce rapid antibacterial action against oral pathogens. UV-vis, FT-IR and SEM confirmed covalent incorporation of catechol and EPL throughout the fibrous matrix. The resulting DHA-EPL nanofibers patch (DHA-EPLNFs) showed <5% hemolysis, no cytotoxicity to human oral keratinocytes, and accelerated scratch closure in vitro. In a Sprague-Dawley rat RAU model, a single application adhered firmly to the ulcer bed, reduced bacterial load by 2-log, shortened inflammatory phase and achieved 95% mucosal regeneration within 6 days, outperforming commercial propolis oral film. Complete patch resorption occurred within 8 days without systemic adverse effects. This multifunctional DHA-EPLNFs patch offers a safe, effective and patient-friendly alternative for recurrent oral ulcer management.