Substrate Chemistry and Morphology Influence the Valvular Interstitial Cells Mechanobiology

Abstract

Calcific Aortic Valve Disease (CAVD) is the most common form of valve disease in the Western world and represents a major healthcare burden. The primary driver for valvular calcification is the differentiation of valvular interstitial cells (VICs) into a diseased phenotype, the osteoblastic-like cells. Another feature of this disease is the significant change in the organization, composition and mechanical properties of the extracellular matrix (ECM) that beside being the result of the dysfunction of the valve cells, seems to contribute to the progression of the pathology altering cellular molecular signaling. Here, we studied the mechanical, morphological and molecular properties of VICs grown on substrated with different surface chemistry and/or mechanical properties, which mimic the valve ECM structure, to highlight the matrix effect on VICs behavior and the role played in calcified tissue formation. Using atomic force microscopy (AFM) and immunofluorescence microscopy we assessed the biomechanics, morphology and the pathway involved in the mechanical stress and in onset of pathology of porcine and human VICs grown on polyacrylamide gels of different stiffness and on variable-geometry carpets of vertically aligned carbon nanotubes. Our results will allow to identify a suitable material for engineering aortic valve artificial scaffolds.