Drug-resistant
bacterial infection of cutaneous
wounds causes great harm to the human body. These
infections are characterized by a microenvironment with recalcitrant
bacterial infections, persistent oxidative stress, imbalance of immune regulation, and suboptimal angiogenesis. Treatment strategies available to date are incapable of handling the healing dynamics of infected
wounds. A
Schiff base and
borate ester cross-linked
hydrogel, based on
phenylboronic acid-grafted
chitosan (CS-PBA), dibenzaldehyde-grafted poly(
ethylene glycol), and
tannic acid (TA), is fabricated in the present study. Customized
phenylboronic acid-modified
zinc oxide nanoparticles (ZnO) are embedded in the
hydrogel prior to gelation. The
CPP@ZnO-P-TA
hydrogel effectively eliminates methicillin-resistant Staphylococcus aureus (MRSA) due to the pH-responsive release of Zn2+ and TA. Killing is achieved via membrane damage,
adenosine triphosphate reduction, leakage of intracellular components, and hydrolysis of bacterial o-nitrophenyl-β-d-
galactopyranoside. The
CPP@ZnO-P-TA
hydrogel is capable of scavenging reactive
oxygen and
nitrogen species, alleviating oxidative stress, and stimulating M2 polarization of macrophages. The released Zn2+ and TA also induce neovascularization via the PI3K/Akt pathway. The
CPP@ZnO-P-TA
hydrogel improves tissue regeneration in vivo by alleviating inflammatory responses, stimulating angiogenesis, and facilitating
collagen deposition. These findings suggest that this versatile
hydrogel possesses therapeutic potential for the treatment of MRSA-infected cutaneous
wounds.