PROJECT SUMMARY Congenital heart disease occurs in about 1% of births, making it the most common type of birth defect and leading cause of infant mortality in the United States. Congenital aortic valve disease, one category of congenital heart disease, frequently requires surgery. Despite generally positive results, undesirable outcomes remain common, and measures of success are typically based on an empirical, retrospective “guess and check” approach. Due to heterogeneous disease, clinical trials are difficult to conduct. Two promising procedures are bicuspidization repair, in which the surgeon constructs a two leaflet valve, and bioprinted valve replacement, a new type of highly experimental prosthetic valve that can potentially grow with the patient. The optimal valve geometry for both pro- cedures remains under debate or unknown. Thus, there is an unmet clinical need for engineering design tools to optimize postoperative valve geometry and improve outcomes. Simulations provide a controllable and efficient means to predict optimal surgical procedures, and after validation, translate guidelines to the clinic. Central to this work is a novel and robust modeling framework for simulating heart valves developed by the applicant, Dr. Alexander D. Kaiser. This research will leverage his modeling methods combined with a multimodal approach including in vitro and human studies to efficiently translate scientific knowledge to the clinic. Dr. Kaiser pro- poses to (1) optimize the postoperative leaflet geometry of bicuspidization repair and bioprinted replacement with simulation-guided design, (2) confirm and validate optimal valve performance in vitro and (3) translate guidelines to the clinic to advise bicuspidization repairs. Dr. Kaiser has extensive previous training in applied mathematics, numerical methods and computational modeling of heart valves. His career development plan includes training in congenital heart disease pathophysiology and methods of surgical treatment, in vitro experimental methods and medical imaging. The Department of Cardiothoracic Surgery at Stanford University will provide an outstanding interdisciplinary environment to enable Dr. Kaiser’s transition from primarily researching applied mathematics to being an interdisciplinary, medical investigator. Mentor Michael Ma is a leading, innovative pediatric cardiac surgeon eager to incorporate new scientific information into his surgical practice. Co-mentor Alison Marsden is a renowned expert in computational modeling of the cardiovascular system. Complementary expertise will be offered by advisors Drs. Ennis (MRI, in vitro testing), Skylar-Scott (bioprinting), Feinstein (pediatric cardiology) and Woo (cardiac surgeon). Dr. Kaiser will receive extensive mentoring, guidance and resources to transition to independence. To conclude, the mentoring, training, research experience and clinical research environment will prepare Dr. Kaiser to become an independent, interdisciplinary medical...