Multifunctional NIR-Responsive Composite Hydrogel with Combinatorial Antibacterial and Regenerative Properties for Diabetic Wound Healing

The management of diabetic chronic wounds (DFUs) is challenging due to persistent bacterial colonization, impaired neovascularization, and disordered inflammation. We engineered a multifunctional photothermal hydrogel (PPCS) by integrating CuS nanoparticles and high-concentration sucrose to establish a dual-action therapeutic cascade: potent antibacterial eradication followed by pro-angiogenic stimulation. Upon NIR irradiation, the PPCS system executes a combinatorial anti-infective mechanism: CuS-mediated photothermal effect and ROS generation are amplified by sucrose’s hyperosmotic pressure, achieving 99.3% bacterial eradication. Beyond sterilization, the hydrogel acts as a Cu2+ sustained-release depot, significantly promoting HUVEC proliferation and migration. This pro-angiogenic effect is mechanistically linked to the upregulation of HIF-1α/VEGF signaling, accelerating neovascularization. Furthermore, sucrose efficiently manages wound exudate, maintaining a repair-conducive microenvironment. In a diabetic rat model, the PPCS dressing demonstrated superior therapeutic efficacy, achieving an accelerated wound closure rate of 99.4% by Day 14, significantly surpassing the control group’s 78.9%. This work presents a tailored hydrogel platform that effectively targets both persistent infection and impaired vascularization, offering a precise and highly efficient therapeutic modality for the clinical management of diabetic chronic wounds.