Multifunctional Hydrogel Microneedle Patches Modulating Oxi-inflamm-aging for Diabetic Wound Healing.

Oxidative stress, chronic inflammation, and immune senescence are important pathologic factors in diabetic wound nonhealing. This study loads taurine (Tau) into cerium dioxide (CeO₂) to develop CeO₂@Tau nanoparticles with excellent antioxidant, anti-inflammatory, and anti-aging properties. To enhance the drug penetration efficiency in wounds, CeO₂@Tau is encapsulated in gelatin methacryloyl (GelMA) hydrogel to prepare CeO₂@Tau@Hydrogel@Microneedle (CTH@MN) patch system. Microneedle technology achieves precise and efficient delivery of CeO₂@Tau, ensuring their deep penetration into the wound tissue for optimal efficacy. Rigorous in vitro and in vivo tests have confirmed the satisfactory therapeutic effect of CTH@MN patch on diabetic wound healing. Mechanistically, CTH@MN attenuates oxidative damage and inflammatory responses in macrophages by inhibiting the ROS/NF-κB signaling pathway. Meanwhile, CTH@MN activated autophagy-mediated anti-aging activity, creating a favorable immune microenvironment for tissue repair. Notably, in a diabetic mouse wound model, the multifunctional CTH@MN patch significantly promotes wound healing by systematically regulating the oxidation-inflammation-aging (oxi-inflamm-aging) pathological axis. In conclusion, the in-depth exploration of the CTH@MN system in this study provides new strategies and perspectives for treating diabetic non-healing wounds.