Stimuli-responsive drug delivery, antioxidant and photothermal antibacterial hydrogel wound dressing for MRSA-infected pressure ulcer repair

Abstract

Chronic wounds, particularly pressure ulcers (PUs), pose a persistent clinical challenge due to infection, oxidative stress, and impaired healing. To address these issues, we developed a smart hydrogel wound dressing based on a dynamic phenylboronate ester network formed between phenylboronic acid-modified hyaluronic acid (HA–PBA) and dopamine-modified hyaluronic acid (HA–DA). This network enables ROS/pH-triggered quercetin release: under inflammatory conditions (pH 5.5 or elevated H₂O₂), the boronate ester bonds cleave, releasing the antioxidant drug quercetin on demand. In addition, the polydopamine (PDA) components confer a PDA-mediated photothermal antibacterial effect; upon 808 nm near-infrared irradiation, the hydrogel rapidly kills >99% of both methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli in vitro. In a mouse model of MRSA-infected pressure ulcer repair, treatment with this hydrogel plus mild photothermal therapy significantly reduced bacterial load, accelerated granulation tissue formation, promoted re-epithelialization, and enhanced angiogenesis, achieving ∼90% wound closure within 14 days. This work demonstrates that integrating dynamic covalent crosslinking, stimuli-responsive antioxidant delivery, and photothermal antibacterial activity into a single platform offers a promising strategy for infected pressure ulcer management.