pH-Responsive multifunctional drug-loaded covalent organic framework hydrogel dressing for enhanced bacteria-infected wound healing

Linarin-loaded covalent organic framework (LN@COF) was synthesized in a single step and integrated into a self-healing, highly adhesive hydrogel, creating a pH-triggered smart drug delivery dressing for treating bacterial-infected wounds. • COF-based hydrogel enables smart, antibiotic-free wound therapy. • pH-responsive LN release enables precise drug delivery. • Dual antibacterial and pro-angiogenic therapeutic effects. • Excellent tissue adhesion and biocompatibility demonstrated. • Effectively promotes healing of infected skin wounds. Pathogen-induced delayed wound healing remains a formidable public health challenge. Traditional smart antibiotic delivery systems that spontaneously generate electrical signals to enhance antibacterial efficacy typically require metal electrodes connected to an external power source, thereby limiting their applicability outside of clinical settings. To circumvent this limitation and eliminate the use of antibiotics and external power sources, we synthesized a linarin-loaded covalent organic framework (LN@COF) via condensation and Schiff base reactions. This LN@COF was integrated into a self-healing and highly adhesive hydrogel through free radical polymerization, developing a pH-triggered intelligent drug release dressing for the promotion of wound healing. The LN@COF hydrogel demonstrates pH-responsive LN release under acidic conditions through protonation, indicating effective drug release in acidic extracellular microenvironments. This pH-triggered sustained release system not only mitigates the burst release issue of conventional drug delivery but also exhibits synergistic antibacterial and angiogenic activities during the repair of infected wounds. In vitro assays demonstrated that LN@COF hydrogel possesses significant antibacterial activity and enhances cell proliferation and migration capabilities. In vivo studies revealed that LN@COF hydrogel not only induced epithelialization, collagen deposition, and angiogenesis processes in promoting of wound healing, but also demonstrating excellent biocompatibility. This study provides a novel approach and significant breakthrough in the design and application of intelligent drug release systems for wound dressings.