Bioelectronic Closed-Loop System for Wireless Wound Healing and Tissue Regeneration

Background: Approximately thirty million people in the United States suffer from diabetes. The prevalence of diabetic foot ulcers (DFUs) in this population is 13%. Current standard of care wound dressings are passive and cannot actively respond to variations in the wound environment. Smart bandages are well positioned to address these challenges with their ability to integrate (bio)sensors for real-time monitoring and active wound care treatment.

There have not been significant advancements in incorporating sensing technologies to deliver active wound care. We believe this can be achieved using a multidisciplinary approach combining electrical and chemical engineering with the fundamentals of biomolecular processes in wound healing.

Methods: A flexible printed wireless stimulator was designed and fabricated to deliver directional energy across a wound gradient. Subsequently a low impedance PEDOT:PSS electrode was designed to optimize the skin and stimulator interface, producing a robust gel with tunable adhesion properties. The smart bandage was evaluated in an excisional diabetic and C57BL6/J murine wound healing model. A parabiosis model was used to evaluate circulating cell migration into the wound bed. Single cell analyses were performed to evaluate changes in cell populations as a direct result of induced electrical stimulation. In vitro validation was performed to elucidate in vivoresults.

Results: Wireless electrical stimulation resulted in significantly accelerated wound closure, when compared to controls, in both a diabetic and C57BL6/J murine excisional wound healing model. Complete epidermal recovery was observed, with a thicker collagen network and increased dermal thickness. Greater neovascularization and appendage formation were observed in the treatment groups. Single cell analyses revealed higher proliferation and remodeling regulatory markers expressed across treated groups. In vitro co-culture validation experiments demonstrated accelerated proliferation, mitotic rate and tube formation when compared to controls.

Conclusion: Our data demonstrates the functionality of a robust wireless interface for wound healing. This novel treatment modality will integrate AI processing components for the development of a closed-loop functional stimulator. By combining the domain expertise of nanofabrication, mechanotransduction, fibrosis and molecular/cellular analyses, we are developing a novel chronically stable and robust smart bandage that will pave the way for the next generation of palliative wound care.