Grants We Funded

Abstract
Diabetic foot ulcers (DFUs) are a serious and prevalent condition affecting over 6.5 million individuals in the U.S. Current management algorithms for DFUs rely on subjective assessments by practitioners, with minimal objective data to guide treatment. Wound care relies heavily on trial-and-error approaches, and targeted therapies are implemented as a last resort with limited efficacy. Combined, this prolongs morbidity and increases overall cost. It is known that the molecular environment of a wound determines the healing process. Thus, several investigative markers in wound fluid are being explored to guide objective assessment of chronic wounds and optimize care for these patients. Current evidence suggests that while individual biomarkers have limited diagnostic value, measurement of multiplexed panels may better predict healing outcomes. Yet 2 major challenges to exist to this end: (1) curating a suitable panel requires extensive refinement and validation – this is challenging with standard assays (e.g. ELISA), which are low-throughput and costly; (2) even if validated biomarkers panels were available, standard clinical assays are not practical for routine decision-making in clinical wound care settings. This application will introduce methods that fill these critical voids in order to streamline development of objective, biomarker panel-based point-of-care tests (POCTs) to assess chronic wounds. We will address the first challenge with the FemtoarrayTM platform we previously developed, comprised of low-cost, inkjet-printed microarrays fabricated on a ‘zero-background' polymer brush coating. Femtoarrays can quantitatively assess ~100 biomarkers with femtomolar sensitivity directly from a drop of fluid over a 5-log range. These will be used to simultaneously assess a 20-plex panel of investigative molecular markers in wound fluid collected from DFU patients at Duke Hospital. In parallel, we will address the second challenge by demonstrating the feasibility of a smartphone-based POCT in a clinical wound care setting. As proof-of-concept, the POCT will test for markers of elevated protease activity, a hallmark of nonhealing. If successful, the information generated in these studies will have a potentially transformative effect on our approach to chronic wound care. Knowledge that a patient harbors a quantitative molecular signature with functional implications in wound healing opens doors to timely, targeted, and personalized management of DFUs.

Biography
David A. Brown, M.D., Ph.D., is a plastic and reconstructive surgeon at Duke University Hospital in Durham, North Carolina. Dr. Brown graduated from the University of California, Irvine School of Medicine and subsequently completed General Surgery residency at University of Washington Medical Center, followed by Plastic and Reconstructive Surgery residency at Duke University Medical Center. He holds a Ph.D. in biomedical engineering and has been active in both basic and clinical research throughout his career. Dr. Brown’s clinical and research interests revolve around wound healing and clinical wound care. He is involved in several hospital committees concerning the care of patients with chronic wounds, and he is part of an active research laboratory investigating novel therapies for wound healing. Dr. Brown currently has 40% protected time to pursue clinical and basic science research. His work is funded in part by the Department of Defense and Duke Department of Surgery.