Project Summary Chronic, difficult-to-heal wounds affect the lives of more than 25 million people with diabetes in the United States, leading to increased healthcare costs and decreased quality of life. Patients with late stage diabetic foot ulcers often progress to amputation for a gangrenous lower extremity limb. Therefore, early stage medical intervention is critical for diabetic foot care. Because of pressure relief, the total-contact cast is the gold standard and most widely used method for healing the most common type of plantar ulcerations (grade 1 ulcers). However, the cast needs to be changed periodically for wound inspection and evaluation, which is burdensome to both patients and providers. Therefore, it is desirable to continuously monitor wounds without direct visualization. Furthermore, because the endogenous electric field is askew or absent in chronic diabetic wounds, cell migration is impeded, often rendering standard wound care inadequate. By mimicking the endogenous electric field, electrical stimulation has been shown in several clinical trials to enhance healing and closure. While many smart wound dressings have been developed to monitor the wound environment, they need regular changes, impeding wound healing. Although skin grafts eliminate the need for removal, they lack sensing capabilities and cannot mitigate infections. Here, the investigators propose to develop and validate paradigm-shifting fully resorbable smart tissue-engineering skin grafts for diabetic wound care. The fully resorbable smart tissue-engineering skin grafts could quantitatively assess the wound environment and concurrently deliver electrical stimulation for enhanced wound healing. The PI Dr. Cheng recently developed skin-conformal electronics to continuously monitor the temperature and moisture levels of the wound, along with the fabrication of biodegradable sensors and electrodes with an essential trace element of zinc on a biodegradable substrate. The anti-bacterial/anti-fungal hydrogels recently developed in co-I Dr. Yang?s lab have been shown to have high wet adhesion for sutureless wound closure with nearly no chronic inflammation. As a clinical microbiologist, co-I Dr. Craft with expertise in microbiology will help guide the clinical relevance. In addition to co-I Dr. Ravnic?s extensive experiences on animal and patient studies with infected diabetic wounds, MD Ulbrecht will also contribute his expertise in diabetic foot care. The investigators will first develop and validate Zn-based temperature/moisture sensors on the anti-bacterial/anti- fungal bioadhesive substrate. After integrating the Zn-based electrode on the bioadhesive, the investigators will investigate the therapeutic function of the smart skin graft via electrical stimulation because of infection reduction and electric field-facilitated migration and proliferation for diabetic wound care. The smart skin graft will substantially improve wound care by quantitative assessment and enhanced treatment of chronic wounds, which can result in next-generation wound care devices to replace the existing wound dressings or skin grafts.