ABSTRACT Diabetic foot ulcers (DFUs) are a prevalent diabetes complications affecting up to 35% of people with diabetes. Considering the continuous increase in diabetes prevalence and incidence reaching pandemic rates worldwide, the healthcare and socioeconomic impact are staggering, with ~80,000 Americans sustaining non-traumatic amputations each year, and five-year mortality rates of up to 40%. Diabetic foot ulcers (DFUs) costs alone are estimated to add $9 billion-$13 billion per year to the rest of costs to manage diabetes. Additionally, after decades of sustained decline, most recent evidence show that non-traumatic lower extremity amputations in diabetes are now on the rise, despite advances in the standards of diabetes care, recognition for the need of interdisciplinary care teams, and research to target wound care products. Thus, continuing the work and expanding our accomplishments during the first cycle of the Diabetic Foot Consortium (DFC) Clinical Research Unit to validate and implement sensitive DFUs biomarkers at the point of care cannot be understated. The main objectives of the DFU Clinical Research Unit (CRU) at the University of Michigan are to expand the work and activities initiated during the first cycle by integrating the robust DFC infrastructure we built at Michigan with the highly skilled clinical and translational research team to: finalize the ongoing DFU biomarkers protocols; implement the DFC master protocol and its various substudies; continue our high recruitment performance across all ongoing and new biomarker studies; recruit, train and supervise satellite sub sites; develop new methods to stimulate participants engagement and adherence; refine large and standardized biological, imaging, and clinical samples collections, including patient reported outcomes and social determinants of health; analyze how DFU recommended standards of care are implemented into usual care; active and effective participation in DFC self-governing committees. Additionally, will participate in biomarker validation analyses and apply novel discovery tools and analyses including machine learning techniques through a multidisciplinary approach to identify new phenotyping, genomic, molecular and microbiome biomarkers from all DFUs biosamples and wound images to be implemented at point of care. We will also leverage the large and diverse pool of people with diabetes foot complications that receive care at the entire University of Michigan Health System, enabling us to recruit for any ongoing and new DFU studies proposed in the renewal. Our continuous participation as a DFC CRU, will enable us to build upon the state-of -the-art infrastructure, and the high record of success and leadership we established over the past four years to continue to impact progress in all facets of DFUs from research, to personalized treatment implementation and prevention, ultimately contributing to the great success of the entire DFC network.