Bilayer Microneedles Loading Nanozymes and Quantum Dots with Gradient Photothermal Antibacterial, Exudate Control, Antioxidation, and pH Monitoring for Enhanced Diabetic Wound Healing
Jingyi Shi, Yifeng Yuan, Kehan Liu, Weizhong Yuan
Abstract
Chronic diabetic wounds are characterized by excessive oxidative stress, persistent infection, immune dysregulation, and excessive exudate, all of which hinder effective healing. However, most current microneedle (MN) platforms overlook exudate management and real-time wound monitoring. Herein, we present a multifunctional hydrogel MN patch composed of gelatin methacryloyl (GM), polydopamine-coated cerium oxide nanozymes (P@C NPs), and nitrogen-doped carbon quantum dots (N-CDs). The bilayer MN structure features a vertical gradient of photothermal P@C NPs, enabling localized antibacterial action and regulation of exudate via balanced hydrogel swelling and water evaporation under near-infrared (NIR) irradiation. Incorporating pH-responsive N-CDs into the backing layer of the GM/P@C/CDs MN patch enables real-time pH monitoring during the early critical healing phase (days 0–3). The fluorescence changes were visible to the naked eye and quantifiable through smartphone imaging. Wound pH rose from 5.4 to 7.4 due to infection but decreased after photothermal treatment, indicating effective bacterial eradication. Due to reversible Ce 3+ /Ce 4+ conversion, P@C NPs exhibit superoxide dismutase (SOD) and catalase (CAT)-like activities, scavenging reactive oxygen species (ROS), alleviating hypoxia, and promoting angiogenesis. Additionally, P@C NPs induce the macrophage transition to an anti-inflammatory phenotype, synergistically improving healing. In vivo, the MN system generated a 23 °C gradient temperature increment under NIR irradiation, reduced the level of exudate, and lowered the pH from 7.4 to 5.9. It facilitated 99.9% wound closure, potent antibacterial activity, enhanced collagen deposition, angiogenesis, and inflammation resolution. This multifunctional hydrogel MN platform integrates gradient photothermal therapy, exudate control, and pH monitoring, offering a promising strategy for advanced diabetic wound care.