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-kappa B 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. CeO2 loaded with taurine is encapsulated into GelMA hydrogel to prepare CTH@MN microneedle patches for diabetic wound treatment. CTH@MN exerts antioxidant and anti-inflammatory effects when acting on macrophages and slow cellular aging by activating autophagy. In a mouse model of diabetic wounds, CTH@MN breaks the vicious cycle of oxi-inflamm-aging, rescues the immune aging microenvironment of local wounds, and ultimately enhances wound healing efficiency. image