Bioinspired Catechol-Nanocellulose/Chitosan Polymeric Hydrogel with Enhanced Wet Adhesion and Antibacterial Activity for Diabetic Wound Healing.

Abstract

Diabetic skin injury is a serious clinical challenge due to impaired healing and infection. Here, we developed a sandcastle worm-inspired hydrogel featuring a phosphate-catechol-amine synergistic network based on a poly(acrylic acid-co-acrylamide) network, functionalized with dopamine-grafted cellulose nanofibers (DA-PCNF) and quaternized chitosan (QCS), to accelerate diabetic wound healing. The hydrogel exhibits strong tissue adhesion (78.82 ± 2.55 kPa) and broad-spectrum antibacterial activity (99.67% killing of Escherichia coli and 99.55% killing of Staphylococcus aureus in vitro). More importantly, it exhibits pH-responsive swelling and adhesion behaviors, maintaining robust adhesion under mildly acidic wound conditions while attenuating adhesion under neutral conditions to facilitate atraumatic dressing removal. Antioxidant assays indicated that the hydrogel exhibits scavenging activity against various free radicals with efficiencies ranging from 30% to 40%, attributable to the catechol groups. In vivo application of the hydrogel to infected diabetic wounds significantly accelerated healing (99.82%, on day 12 after Pseudomonas aeruginosa-infected wound formation), with reduced inflammation and enhanced tissue regeneration. These findings demonstrate that the catechol-nanocellulose/chitosan polymeric hydrogel effectively overcomes adhesion, infection, and oxidative stress barriers in diabetic wound healing, making it a promising candidate for difficult-to-heal chronic ulcers.