PROJECT SUMMARY – OVERALL We propose to establish the Center for Cardiovascular Research in Biomechanics (CRiB), which will provide a foundation for synergistic translational research activities aimed at developing novel materials and devices to treat cardiovascular diseases. To maximize impact, the initial set of projects will focus on Peripheral Arterial Disease (PAD) of the lower extremity arteries because PAD treatments continue to disappoint despite decades of improvements and refinements in technologies and pharmacological adjuncts. The high rate of treatment failures makes PAD one of the most expensive vascular diseases to treat on a per-patient basis, increasing the urgency of developing better biomedical materials and devices. Our team has done extensive research in PAD, and the strength of our approach is in the use of human tissues, large preclinical animal models, and diverse multidisciplinary collaborations that enable the direct clinical translation of our discoveries. Support of the COBRE will help us build a unique research environment with infrastructure to attract and train scientists in translational cardiovascular biomechanics research. Our CRiB Center will be directed by a senior NIH R01- funded investigator Dr. Alexey Kamenskiy who has built one of the largest databases of interlinked mechanical, structural, and demographic characteristics of human arteries and used it to develop novel solutions to improve clinical outcomes of vascular disease treatments. The CRiB Center will also include a unique Tissue Analysis Core (TAC) dedicated to performing mechanical, structural, and biological evaluations of human, large animal, and man-made materials, and directed by an NIH R01-funded scientist Dr. Anastasia Desyatova. The TAC will support three projects by Research Project Leaders (RPLs) focused on the effects of sex on vascular elastogenesis (RPL Majid Jadidi) and the development of devices for PAD surgical treatment and post-treatment recovery using novel elastomeric bypass grafts (RPL Kaspars Maleckis) and ischemic wound dressings (RPL Yury Salkovskiy). All three projects are based on solid preliminary data from humans and large animals and are led by tenure-track Assistant Professors. Each RPL is mentored by two seasoned investigators: an NIH R01- funded clinician-scientist to ensure translation, and a world-famous basic scientist from the RPL’s field of expertise to advise on research strategy. The focus of our Center on research supporting the development of devices and materials for vascular disease treatment is different from more traditional cellular and molecular- based approaches and strategically utilizes our strengths in human artery biomechanics. With the help of the COBRE, CRiB will create a novel biomedical research infrastructure with a direct translational focus that will strengthen the technological and intellectual potential of our university, attract and retain talent, increase interactions with the biomedical device industry, support many existing IDeA programs, and provide significant benefits for the health of Nebraskans and society at large.

PROJECT NARRATIVE – OVERALL We propose establishing the Center for Cardiovascular Research in Biomechanics (CRiB), which will support research aimed at the development of novel biomedical materials and devices to treat cardiovascular diseases. Our CRiB Center encompasses a robust mentoring program for junior investigators, a unique Tissue Analysis Core, and three research projects focused on the effects of sex on vascular elastogenesis and the development of novel materials and devices for Peripheral Artery Disease surgical treatment and post-treatment recovery using elastomeric bypass grafts and ischemic wound dressings.