Dynamic phase-adaptive hyaluronic acid hydrogel with bacterial capture and on-demand removal for drug-resistant bacteria-infected wound healing.

The purpose of this study is to address the issue of chronic, recalcitrant wounds caused by excessive inflammatory responses when irregular wounds become infected with bacteria. The study developed a hydrogel that combines intelligent response properties with multiple therapeutic functions. Hydrogels have a unique intelligent viscoelasticity through the construction of dynamic boronic ester bonded crosslinked networks. At low frequencies (0.01 Hz to 1 Hz), the hydrogel assumes a viscous fluid state and is able to dynamically phase-adapt to fill irregular wounds like a "liquid patch". And in the high-frequency state (10 Hz to 100 Hz), the hydrogel transforms into an elastic solid state that provides both mechanical support and protection of the wound tissue. This study designed a glucose/H₂O₂ dual-response removal strategy, which precisely cuts the cross-linking points of the topological network and empowers on-demand and painless removal of the hydrogel. The modified phenylboronic acid moiety on the surface of the hydrogel constitutes a "molecular trap" that specifically recognize and capture bacteria. Combined with the non-specific killing mechanism of oligo-polyethyleneimine (OEI) on bacteria, this hydrogel can efficiently purify the wound environment and break through the bottleneck of bacterial drug resistance. This effectively relieved the inflammatory cell infiltration at the lesion and coordinated the process of angiogenesis and re-epithelialization. Through the triple action mechanism of "capture-kill-regulate", it provides a novel solution to ensure stable healing of irregularly damaged skin with bacterial infection.