Abstract
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 Cu(2+) 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.