Injectable, pH-Responsive Chitosan/Tannic Acid/PCN-224 Nanocomposite Hydrogels with Synergistic Phototherapeutic and Antioxidant Properties

Abstract

Diabetic wounds remain difficult to treat due to bacterial resistance, a localized weakly acidic microenvironment, imbalanced oxidative stress, and poor dressing conformity. To address these challenges, this study developed an injectable pH-responsive nanocomposite hydrogel using phenylboronic acid-modified chitosan (PBCS), tannic acid (TA), and porphyrinic metal–organic framework PCN-224 nanoparticles, featuring with superior tissue adhesiveness, self-healing, and pH-responsiveness. The hydrogel was fabricated using PBCS as the matrix and TA as the cross-linker, establishing a dual-cross-linked network sustained by dynamic boronate ester bonds and multiple hydrogen bonds, into which the porphyrinic metal–organic framework (MOF) PCN-224 was subsequently loaded. This hydrogel precisely senses and exploits the endogenous weakly acidic microenvironment of the infected wound, triggering the dissociation of boronate ester bonds to achieve the on-demand release of TA, as well as the smart regulation of the network’s swelling behavior. The synchronously released polyphenol component, TA, imparts excellent antioxidant activity to scavenge excess free radicals and re-establish oxidative stress balance. Meanwhile, under 660 nm laser irradiation, PCN-224 generated reactive oxygen species and a mild photothermal effect, enabling combined photodynamic and photothermal antibacterial activity. Collectively, the PBCS-TA/PCN-224 nanocomposite hydrogel integrates pH-responsive behavior, antioxidant activity, and light-triggered antibacterial functionality, supporting its potential application in infected diabetic wounds.