Biological sex influences normal physiology and the manifestation of disease. Severe illnesses such as cardiovascular diseases and cancers can exhibit profound sex differences in their occurrence, progression, and response to treatment. Historically, the research models used in preclinical science to develop new drugs do not sufficiently account for sex differences. For example, lab experiments testing new drug compounds typically do not examine effects in both female (XX sex chromosomes) and male (XY sex chromosomes) cells. This is due in part to the absence of distinct methods for culturing female and male cells with the right combination of sex hormones such as estrogen and testosterone. This CAREER project will explore research and development of sex-based human cell culture methods and engineered tissue models. The research will be integrated with university education and K-12 outreach that emphasizes the roles of individual biological differences such as age, sex and genetic background in health and disease, thereby helping students connect with medical science research. Principles of sex-based biology and medicine will be integrated in undergraduate and graduate physiology curricula in biomedical engineering. Completion of the proposed research will deliver female and male culture medium formulations with defined sex hormone compositions and engineered tissue models for studying sex differences in the retina, skin, and other organs. Collectively, these broadly adoptab