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<p>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 H<sub>2</sub>O<sub>2</sub> 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 Fe<sup>2+</sup>/Fe<sup>3+</sup> 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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月2日

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  • Wenshuai Li,
  • Lulu Wang,
  • Hui Zhao,
  • Rui Zhang,
  • Yinyin Zhang,
  • Sen Lin,
  • Haoyang Qin,
  • Xianlong Zong,
  • Kang Gan,
  • Junjie Wang,
  • Heng Yin,
  • Yazhou Chen,
  • Rui Li

摘要

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.

Graphical Abstract