Creation of disease-inspired biomaterial environments to mimic pathological events in early calcific aortic valve disease

Significance Due to an insufficient understanding of the mechanisms that drive its progression, there is currently no treatment for calcific aortic valve disease (CAVD) other than valve replacement. In this report, we describe the generation of engineered environments that mimic features found in early CAVD. By combining these engineered models of valve disease with other exogenous cues present during CAVD, we were able to propose a previously unidentified cascade of pathological events and identify specific extracellular components that are critical in regulating this process. These findings demonstrate the utility of engineered in vitro models to perform systematic, controlled studies of events related to disease progression that may lead to future identification of potential targets for therapeutic interventions.