Aortic valve stenosis (AVS) is a disease that causes hardening of the valve, leading to impaired function and ultimately replacement. Currently, the only valve replacements are made of rigid, synthetic materials or decellularized xenografts, both of which cannot repair or growth with younger patients. With tens of thousands of replacement surgeries being completed annually in the United States, this is an area of medicine that would benefit from a better understanding of this disease for potential preventative treatments or engineered, regenerated valve tissue for a replacement that could grow and repair itself.
Until recently, AVS was thought of as a wearing out of the valve tissue with patient age. However, it is now understood to be actively mediated by the resident cells, valvular interstitial cells (VICs). VICs are generally found in a quiescent fibroblast state that can be activated to a secretory myofibroblast phenotype when the valve is injured. These myofibroblasts are critical in repairing the valve to maintain function, but with repeated valve injury, the regulation of the myofibroblast phenotype can be lost and lead to excess matrix deposition, hardening of the valve, and eventually, further differentiation of the VICs into osteoblasts (i.e., bone cells).
Our group is trying to understand the biology of AVS and the signaling pathways and cues associated with healthy versus pathological phenotypic changes seen in VICs. To do so, we are using PEG based hydrogels so that the biophysical and biochemical microenvironment may be acutely controlled based on the hypothesis at hand.