Abstract Diabetic foot ulcers (DFUs) are a prevalent diabetes complications affecting up to 25% of patients and leading to ~80,000 Americans having non-traumatic amputations each year, with five-year mortality rates of up to 40%. Recent evidence suggests that non-traumatic lower extremity amputations are on the rise, after decades of decline, in spite of advances in targeted wound care products, establishment of interdisciplinary clinical and surgical teams, and improving diabetes medical care. Given the worldwide epidemic of diabetes, the burden associated with DFU are high, including high costs of $9 billion-$13 billion per year and besides those associated with high morbidity and mortality. Thus, the establishment of a Diabetic Foot Consortium comprised of experienced DFU Clinical Research Units (CRU) for reliable DFU biomarker discovery cannot be understated. The main objective of this proposal is to integrate the robust infrastructure at Michigan Medicine with our highly skilled clinical and translational team to establish a DFU CRU as a strong contender and contributor within the DFC network that will be uniquely poised to participate in all DFU biomarker discovery and related wound healing projects undertaken by the Consortium. Additional aims are to The aims are to : identify, recruit, and phenotype a broad spectrum of DFU participants from the large base of patients with these conditions who are currently being followed at Michigan Medicine, according to the Consortium requirements; implement standardized mechanisms and protocols for effective longitudinal sample collection and retention; and actively participate in the DFC intellectually and provide all available resources to develop and support clinical study protocols to validate DFU biomarkers, including complex quantifications of wound image features; single cell, genetic, molecular, metabolomics, and microbiome analyses; and assessing additive predictors of DFU healing beyond clinical markers alone using multi-modal approaches. The expected outcome of this work is that the Michigan Medicine DFU Clinical Center will be an integral part of the Consortia collaborative network, with a highly positive impact for the entire spectrum of biomarker discovery and future novel therapies projects.