The Feasibility of Combining Focused Ultrasound and Copper-Cystine Biohybrid for Diabetic Wound Healing

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.

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.

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.

The synergistic treatment of CuHARS-FUS supports rapid macrovascular structure formation and proper cellular differentiation, leading to granulation tissue formation by providing a controlled mechanism for tissue remodeling during the entire healing phase of diabetic wound healing, starting from an enhanced angiogenic activity and bactericidal effect via the CuHARS through Cu²⁺ 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.