A novel and efficacious electrotaxis system for enhancing chronic wound healing - PROJECT SUMMARY. Chronic wounds (CWs) are currently affecting 1 – 2% of the population in the U.S. They have a devastating impact on patients’ health, functional status, and overall quality-of-life. CWs are characterized by delayed skin tissue regeneration processes due to the impaired cell migration of dermal fibroblasts, vascular endothelial cells, and keratinocytes in CWs. Current clinical standard-of-care does not specifically correct these physiological impairment. More advanced treatments, such as growth factors, microRNA-targeting therapies, and stem cells have shown a better efficacy in enhancing cell migration and skin tissue regeneration. However, they face challenges of low efficacy in human patients, inefficient delivery and low stability of therapeutics, and high cost. Due to the limitations of the current CW therapies, there is a critical need for novel treatment technologies that can be easily applied to CWs and efficaciously enhance cell migration and skin tissue regeneration without imposing a high financial burden on patients. Direct current (DC) electric field (EF) is capable of guiding directional migration and increasing the migration speed of keratinocytes, dermal fibroblasts, and vascular endothelial cells in vitro, a phenomenon called electrotaxis. Electrotaxis has also led to accelerated wound closure in in vitro scratch wound healing assays. Compared to the current technologies, electrotaxis provides unique advantages including highly directional cue for guiding cell migration, rapid cellular responses, easy treatment application, programmable treatment parameters, and low cost. Despite the successful application of electrotaxis in in vitro, the in vivo wound healing efficacy of electrotaxis is limited and insignificant. The reason for this low efficacy is that the DC EF strength that is effective in in vitro cannot be safely applied to in vivo wounds using the conventional electrical stimulation (EStim) electrodes without inducing tissue damage. Our long-term goal is to develop safe and efficacious EStim-based technologies for the CW treatment. Toward this goal, our lab recently developed a hydrogel ionic circuit (HIC) electrode that can safely apply high-strength DC EF to biological tissues by minimizing electrochemical reaction-induced interfacial pH and temperature changes. Our main objective in this proposal is to develop a novel wearable HIC-based electrotaxis system with a high flexibility and a reduced size to facilitate the healing of CWs. Our central hypothesis is that our wearable HIC-based electrotaxis system can safely apply high-strength DC EFs to promote directional migration of keratinocytes, dermal fibroblasts, and vascular endothelial cells into CW at increased speed, which will lead to accelerated CW healing. Our Specific Aims are: 1) to develop a wearable HIC-based electrotaxis system that can safely apply high-strength DC EF to induce electrotaxis cell migration; 2) to determine the in vivo safety and efficacy of our wearable HIC electrotaxis system in enhancing CW healing. If successful, our high-impact technology has the potential to enhance the clinical treatment efficacy of CWs, reduce the amputation and mortality rate, reduce the financial burden on patients, and improve the overall quality-of-life of CW patients.
