Chronic diabetic ulcers are a major complication of diabetes and are characterized by dysregulated molecular and cellular wound microenvironment and persistent inflammation. However, despite tremendous research effort, there is still no effective treatment that is able to directly address the complexity of non-healing diabetic ulcers. Electric field-based therapies have the potential to improve healing of hard-to-heal wounds. However, widespread acceptance of electrotherapies to treat chronic ulcers has been prevented by a lack of standardized protocols, variability in healing outcomes and the need for electrode contact with the skin which is not compatible with standard of care.

The long-term goal of our research is to develop, a novel wireless, electric field (EF) therapy to treat chronic diabetic ulcers. Recent studies by our group have discovered a modality of high-frequency wireless EF (Patent:​ US20150080784A1) that enhances angiogenesis and may be promising for treatments of chronic wounds because it can directly address two major problems of chronic ulcers- insufficient wound vascularization and excessive inflammation.

The objective of this study is to determine the effects of this EF stimulation on healing of the wound, wound neovascularization, and inflammation using a porcine model:​ normal and type I diabetic (streptozotocin, STZ-induced). Our central hypothesis is that the optimally designed EF will penetrate the wound tissue and improve healing by enhancing vascularization and reducing inflammation.

We developed a 3D theoretical model for therapeutic EF wound stimulation and signal optimization. We used the optimized setup to determine the effects of electric field therapy on wound healing in normal (acute) and diabetic (Type I STZ induced diabetes) porcine models.

Our results demonstrate that the EF therapy promotes regenerative healing of normal and diabetic wounds, likely via markedly (two-fold) improved vascularization, attenuated inflammation and a significant reduction in the wound area and scar area. Importantly, EF therapy resulted in significantly improved tissue structure similar to that of the normal skin, demonstrating the potential of this therapy to reduce ulcer recurrence that is often associated with impaired quality of repair tissue. This study shows iii that EF stimulation significantly improves both temporal wound healing progression (earlier wound closure), and functional outcome (epidermal structure regeneration and restoration of functional strength), as compared to controls.

The significance of this study is that it addresses the important clinical problem of non-healing diabetic wounds using a non-contact wireless EF stimulation to improve healing via cell activation in the wound. The proposed therapy is simple-to-use, non-invasive and compatible with standard of care, speeding its translation into clinical trials. The impact of this translational research is that it will provide means to approach the problem of impaired diabetic wound healing from a new perspective, i.e., to use systematic, step-by-step augmentation of the ulcer microenvironment via EF-based wireless therapy. We expect that these preclinical studies will validate the full potential of the EF technology and translate our lab-bench scientific discovery to a regenerative therapy for chronic and diabetic wounds.