Development of an aminoguanidine hybrid hydrogel composites with hydrogen and oxygen supplying performance to boost infected diabetic wound healing.

Diabetic wounds tend to develop into non-healing wounds associated with a complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. This study developed a multifunctional hydrogel system by integrating aminoguanidine and hydrogen and oxygen gas-release nanoparticles (PAP NPs) into phenylboronic acid-modified quaternized chitosan and an oxidized dextran network. Hollow mesoporous Prussian blue (HPB) nanozymes with superoxide dismutase- and catalase-like activities are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous hydrogen peroxide (HO) into oxygen in diabetic wounds. Simultaneously, incorporating ammonia borane (AB)-loaded HPB NPs served as a source of hydrogen, further reducing ROS overproduction and modulating pro-inflammatory cytokine responses. Aminoguanidine in the hydrogel network inhibits the formation of advanced glycation end products (AGEs), inhibiting skin cell apoptosis and promoting their proliferation and migration. Moreover, the hydrogel exhibited significant mechanical characteristics and self-healing capacity owing to the Schiff base and phenylboronate ester linkages. Incorporating PAP NPs into the hydrogel produced an exceptional photothermal response, effectively eradicating bacteria with a mortality rate exceeding 95 % within 10 min and protecting the wound from potential infections. In vivo studies demonstrated that PAP@Gel significantly accelerated the healing of infected diabetic wounds by mitigating oxidative stress, enhancing oxygenation, inhibiting inflammation and AGE formation, and reversing bacterial infections. This study highlights a promising nanomedicine approach for designing future diabetic wound dressings, providing a novel strategy for catalytic ROS scavenging and synergistic hydrogen and oxygen therapies.