Antioxidant-sealed chitosan nanofibers loaded with erythromycin: Tissue regeneration biomaterials with immune-modulating effects in a rat model

Chitosan-based nanofibers hold great promise as advanced biomaterials for controlled drug delivery and tissue regeneration. This study explores a novel class of chitosan-quaternized chitosan nanofibers engineered for enhanced antimicrobial and antioxidant activity, as well as tissue compatibility. The fibers were developed in four variations: unmodified, erythromycin-loaded, surface-functionalized with a vanillin isomer via imine bonds, and a dual-modified formulation combining both modifications, to evaluate the impact of each component on the fiber properties. Extensive physicochemical analysis confirmed the formation of nanofibrous, biodegradable and highly absorbent mats capable of adapting to different wound environments. The imine-based dynamic modification provided controlled drug release, while enzymatic degradation and bioadhesion properties positioned these fibers as promising candidates for sustained therapeutic action. Biological assessments highlighted the fibers' ability to control microbial infections, neutralize oxidative stress, and modulate key immune responses. In vivo implantation in rats demonstrated excellent biocompatibility, with no signs of adverse inflammatory reactions or systemic toxicity. Notably, combining ERY and vanillin contributed to a balanced immune response, reducing inflammatory markers while preserving cellular defence mechanisms. Overall, this study highlights the potential of chitosan-based fibers functionalized with antibiotics and natural antioxidants via imine bonds as biodegradable, immunomodulatory biomaterials for tissue repair.