Fibrotic aortic valve stenosis (FAVS) is a disease characterized by the fibrotic thickening of the valve leaflets that affects 2% of the population over 65 years of age. The inability to detect early stages of FAVS make valve replacement surgery the only viable treatment, motivating research aimed at better understanding the causes that lead to FAVS and its progression. The primary resident cell type in the aortic valve has a quiescent fibroblast phenotype but transitions to a myofibroblast phenotype in response to injury in an attempt to regulate valve homeostasis. Fibrosis occurs when this wound healing process becomes misregulated, but the causes of this are not fully understood.
My research focuses on using 3D synthetic hydrogel cell cultures to understand the effect of biochemical cues on their phenotypic transition to study disease progression. To do so, I encapsulate valvular interstitial cells (VICs) within MMP-degradable hydrogels and assess their response to various cytokines present during the wound healing response (such as TGF-b1, FGF-2 and TNF-a). Culturing cells in 3D provides them with a platform that better recapitulates aspects of their native environment and allows the study of cell contraction development, a key myofibroblast property. To assess cellular response, I measure morphological changes, proliferation, gene and protein expression as well as contractility at different timepoints. Thus, identifying phenotypical changes at different timepoint to give insight into FAVS disease progression.