Bi2WO6@Cu2O-GOx bio-heterojunctionp-n spray for accelerating chronic diabetic wound repairment with bilaterally enhanced sono-catalysis and glycolytic inhibition antisepsis

Biomaterials. 2024 Dec 24:317:123046. doi: 10.1016/j.biomaterials.2024.123046. Online ahead of print.

Abstract

Chronic diabetic wound poses a pressing global healthcare challenge, necessitating an approach to address issues such as pathogenic bacteria elimination, blood sugar regulation, and angiogenesis stimulation. Herein, we engineered a Bi2WO6@Cu2O-GOx bio-heterojunction (BWCG bio-HJ) with exceptional cascade catalytic performance and impressive sonosensitivity to remodel the wound microenvironment and expedite the diabetic wound healing. Specifically, the Z-scheme junctions of Bi2WO6@Cu2O significantly augmented carrier separation dynamics, leading to the highly efficient generation of reactive oxygen species (ROS) upon US irradiations. Furthermore, glucose oxidase (GOx) grafted on the Bi2WO6@Cu2O surface facilitated the conversion of glucose into H2O2 and glucuronic acid, providing a rich supply for Cu+-mediated Fenton-like reactions. The robust oxidation effect disrupted the bacteria's phosphotransferase system (PTS), hindering glucose uptake, glycolysis, and energy metabolism, ultimately inducing bacterial death and reshaping the diabetic wound microenvironment. The BWCG bio-HJ was formulated as an antibacterial spray for chronic diabetic wound repair. Extensive in vitro and in vivo experiments confirmed that the BWCG bio-HJ spray could eliminate pathogenic bacteria, consume local blood sugar, and promote angiogenesis, collagen deposition, and epithelialization, thereby accelerating the diabetic wound healing process. This bio-heterojunction spray comprehensively addressed the principal pathological factors associated with diabetic wounds, offering a promising strategy for combatting stubborn infections.

Keywords: Angiogenesis; Bio-heterojunction; Chronic diabetic wound; Diabetic wound microenvironment; Epithelialization.