Enhanced Wound Healing Through Nanogenerator-Driven Self-Activated Electrical Stimulation - Project Summary The objective of this proposed project is to obtain a cellular-level understanding of how nanogenerator (NG)- driven electrostimulation (NG-ES) achieves accelerated wound healing in multiple clinically-relevant models under both normal and ischemic conditions, and identify the optimal signal and device design that will deliver the desired therapeutic effect. In the US, more than 6.5 million people are affected by chronic wounds, resulting in >$25 billion in annual healthcare expenditures. Low-cost, effective, safe, painless, and easily deployed approaches to wound care are urgently needed. Recent studies have shown that ES significantly enhances cellular processes related to wound healing. However, current ES devices for wound healing, due to their complexity in design and operation, are impractical for daily routine use in patients. Leveraging the state-of-the- art wearable NG technology to replace the bulky and rigid battery and related electronics, this project aims to bring the ES technology from a high-cost, high-maintenance technical niche to an over-the-counter disposable Band-Aid®-like bandage. This project is based on an intriguing new discovery from the collaborative work of PIs Wang and Gibson, demonstrating that the NG-ES vastly improved acute wound healing time in both rodent (from 15 to 3 days) and human skin xenograft models (from >30 to 7 days). We further hypothesize that the transient charge-limited electric fields generated by NG-ES are safe and effective for increasing the rate of normal re- epithelialization, recruitment of fibroblasts, extracellular matrix generation, and neovascularization in human skin wound healing. The proposed research is therefore designed to systematically investigate the therapeutic effect for chronic wound healing from the cellular and tissue level to large animal models, and to establish scientific and engineering support to the NG-ES effects. In Aim 1, we will perform in vitro cell culture studies of the major human skin cell types in the wound environment to establish the cellular mechanisms guiding NG-ES wound healing. We will also identify the optimal electric field strength and frequency in these cellular responses, and demonstrate the superior effect of NG-ES compared to conventional ES signals. In Aim 2, we will evaluate NG- ES effects in two complementary human tissue models that mimic the wound healing environment of human skin: whole ex vivo human skin model and in vivo human skin xenograft model, to understand the impacts from the human skin microenvironment, and in a living systemic environment, respectively. In Aim 3, we will scale up and optimize the NG-ES design and integrate with a medical bandage to deliver desired ES signals over a large skin area on pigs and quantify the enhanced wound healing therein. This project will reveal how wounds respond to low-frequency and charge-limited electric fields produced by NGs locally, and provide the preclinical and engineering data necessary to move rapidly into human clinical trials. Success of this research will lead to a new and effective technology for treating both acute and chronic wounds which is low-cost, sustainable and disposable, and thus applicable worldwide, including in austere and resource-poor locations.
