The feasibility of combining focused ultrasound and copper-cystine biohybrid for diabetic wound healing.

OBJECTIVE: Chronic wound healing, particularly in diabetic wounds, remains challenging due to the lack of effective therapeutic procedures. Pharmacological treatments are often limited by physical side effects, while surgical procedures carry a risk of site infections. This study aimed to provide an overall complete therapeutic regimen for faster diabetic wound healing through focused ultrasound (FUS) in conjunction with localized copper-cystine biohybrids. METHODS: In the current study, we investigated the feasibility of combining FUS performed at 1 MPa, 2500 cycles, 10% duty cycle, 20 Hz pulse repetition frequency and 15-min treatment durations every alternate day over 14 d with localized copper-cystine biohybrid (copper high aspect ratio structures [CuHARS]) treatment, which is a metal-organic biohybrid capable of promoting angiogenesis and exerting a bactericidal effect on wound healing. Therapeutic efficacy was evaluated in diabetic mice with surgically induced dermal wounds using three treatment groups: combined CuHARS-FUS, CuHARS-only and FUS-only over 7- and 14-d periods. RESULTS: The results showed that CuHARS-FUS treatment for 14 ds achieved complete wound closure, whereas the CuHARS-only, FUS-only and control groups exhibited partial or no healing. CONCLUSION: ions-based catalytic decomposition of S-nitrosothiols to nitric oxide and the continuation of endothelial activity through enhanced nitric oxide production due to FUS treatment.