Multifunctional self-healing and pH-responsive hydrogel dressing based on cationic guar gum and hyaluronic acid for on-demand drug release

Pathogen invasion and persistent inflammatory storms caused by bacterial infections are the main challenges to the healing of infected wounds. Herein, this study proposed a pH-responsive polysaccharide hydrogel dressing (CG-HA) composed of cationic guar gum (CG) and hyaluronic acid (HA). Additionally, Zn2+ and ferulic acid (FA)/(3-cyclodextrin ((3-CD) inclusion complexes (FA/(3-CD) were co-introduced into the CG-HA hydrogel to form the desired FA/(3-CD@CG-HA-Zn hydrogel. The FA/(3-CD@CG-HA-Zn hydrogel was constructed based on multiple non-covalent interactions, including electrostatic interactions, coordination bonds and hydrogen bonds, allowing it to conform to irregular wound shapes. Notably, the release rates of FA and Zn2+ at pH 7.5 were faster than those at pH 5.5, indicating that the FA/(3-CD@CG-HA-Zn hydrogel exhibited excellent pH responsiveness and enabled intelligent drug release. Moreover, the inclusion of FA and Zn2+ endowed the hydrogel with robust antibacterial activity against S. aureus (97 %), MRSA (94 %), and E. coli (95 %). Finally, the FA/(3-CD@CG-HA-Zn hydrogel demonstrated efficacy in promoting wound healing by modulating the immune microenvironment and accelerating vascularization. Thus, the developed self-healing FA/(3-CD@CG-HA-Zn hydrogel with pH-triggered on-demand drug release is a promising wound dressing for the management of infected wounds.