ROS-targeting heterojunction-integrated GelMA microneedles for photo-responsive antioxidative action and accelerated diabetic wound healing

<b>Background:</b> Excessive oxidative stress activation in diabetic chronic wounds causes ongoing inflammation and cell dysfunction, which greatly impairs healing. Heterojunction photocatalytic nanozymes can potentially scavenge reactive oxygen species (ROS), but their clinical application faces challenges due to low photocatalytic efficiency, poor biocompatibility, and limited stability in physiological environments. <b>Methods:</b> APTES-COF-1@MXene heterojunction nanozymes (AC-1@MXene) were synthesized using chemical methods combined with in-situ growth techniques. Double-layered hydrogel microneedle systems (ACMGM) were fabricated through UV polymerization with tips loaded with AC-1@MXene. The photocatalytic performance of the nanozymes was assessed using physicochemical methods. Biocompatibility was confirmed through biochemical assays, and the therapeutic effectiveness of ACMGM was evaluated in diabetic mouse wound models. <b>Results:</b> AC-1@MXene multifunctional photocatalytic nanozymes were successfully developed, exhibiting both catalase and superoxide dismutase activities. These nanozymes demonstrated significantly enhanced enzymatic activity under visible light, efficiently converting H₂O₂ and ·O₂ ^- into H₂O and O₂, thus providing strong antioxidant protection. <i>In vitro</i> tests confirmed excellent biocompatibility, while <i>in vivo</i> studies showed that ACMGM microneedles effectively facilitated transdermal delivery of nanozymes. This significantly aided diabetic wound healing and reduced local oxidative stress. Mechanistic insights revealed that tissue regeneration and repair resulted from synergistic effects, including anti-inflammatory actions, M2 macrophage polarization, angiogenesis, and increased collagen synthesis. <b>Conclusion:</b> The ACMGM microneedle system effectively delivers nanozymes through the skin and enhances their catalytic activity upon exposure to visible light. This precisely modulates the oxidative stress microenvironment in refractory wounds, offering an innovative therapeutic strategy for diabetic wound treatment.