pH-Triggered antibiotic release from nanofiber–hydrogel hybrid dressings for infected wound healing

Wound dressing provides a temporary barrier membrane against hemostasis and external infections, and subsequently serves as an induction template to guide tissue remodeling, highlighting the need for an efficient and streamlined design to accelerate the healing process. Herein, we report the development of a mechanically robust, biocompatible gelatin-based hydrogel dressing integrated with pH-responsive nanofibers for sustained and targeted antibiotic release. The nanofibers, fabricated <i>via</i> electrospinning and loaded with amoxicillin, exhibited pH-triggered release profiles responsive to acidic wound environments. A Schiff base reaction between aldehyde-modified guar gum and gelatin conferred enhanced mechanical strength without compromising biocompatibility. This hybrid structure enabled a dual-stage release mechanism, characterized by an initial release from the nanofibers and subsequent sustained diffusion from the hydrogel matrix. This sequential release profile resulted in a more than 10-fold extension of the release duration compared to the control. In a murine wound infection model, the composite dressing significantly accelerated healing, reducing the healing time by at least 50%. Additionally, it suppressed inflammatory cytokines and promoted collagen deposition. This study presents a practical strategy for developing multifunctional, bioresponsive wound dressings with customizable release behavior tailored to the dynamic wound microenvironment.