MXene-integrated microneedles reprogram diabetic-associated macrophages for deep-wound infection therapy and immunoprotection

Traditional hyperthermia-boosted photothermal therapy (PTT) for infected wounds often suffers from thermal damage to healthy tissue, exacerbates immune dysregulation, and compromises antibacterial efficacy in deep tissue. Here, we developed a functional microneedle system (MTF@MNs) by incorporating MXene-tannic acid/iron (MXene-TA/Fe, MTF) nanosheets into a photocrosslinkable GelMA/PEGDA hydrogel matrix. The engineered microneedle architecture facilitates targeted delivery of therapeutic nanosheets into deep, biofilm-rich subcutaneous regions, which are characterized by elevated H₂O₂ levels, acidic pH, and poor drug permeability. Under mild near-infrared (NIR) irradiation, MTF@MNs synergistically enhance the peroxidase-like nanozyme activity of MXene-TA/Fe while accelerating Fe²⁺/Fe³⁺ release, facilitating efficient eradication of deep-tissue infections without thermal injury. Our results demonstrate that MTF@MNs not only exhibit robust reactive oxygen species (ROS) scavenging capacity, but also promote macrophage polarization toward pro-regenerative phenotypes. Furthermore, they attenuate pro-inflammatory cytokine release by inhibiting the TNF/MAPK signaling pathway in macrophages. Collectively, the MTF@MNs system accelerates infected wound healing through reprogramming the immune microenvironment, enhancing collagen deposition, and stimulating angiogenesis, thus offering a promising strategy for the management of deep-tissue infections.