Enabling Technologies in Vascular Biology: Microphysiological Systems, Organoids, and Beyond.

Vascular and cardiovascular diseases are leading causes of mortality globally. Despite significant progress in elucidating the molecular and cellular mechanisms involved in these conditions, some critical aspects, including complex intercellular interactions and therapeutic efficacy, require further investigation to be fully understood and predicted. This lack of knowledge motivates the development of advanced research methodologies, where bioengineering has contributed significantly. Technological advances in bioengineering have evolved into powerful tools that replicate the molecular and cellular microenvironment of human vascular and cardiac tissues with unprecedented fidelity in vitro and ex vivo. The evolution of conventional 2-dimensional, monocultured cell models into 3-dimensional and mechanically dynamic models that also possess tissue-level cellular and molecular sophistications enables studying vascular pathologies and therapies with promising predictability. Various techniques, such as microphysiological systems, organoids, and bioprinting, are increasingly used and further improved through numerous studies to reconstruct human vascular microenvironment and the associated diseases such as atherosclerosis and thrombosis in vitro. Despite these advancements, there are still challenges with each of these methods in addition to the knowledge gaps left for future research. This review takes a critical approach to comprehensively review existing reports and the most recent progress in the application of cutting-edge in vitro and ex vivo technologies for vascular biology and pathology. More importantly, it highlights the challenges and research gaps that will require future research to be addressed.