Influence of collagen fiber architecture on calcific aortic valve disease progression

To understand the causes and progression of calcific aortic valve disease (CAVD), several in vitro models were studied using non-invasive imaging techniques. Explanted rat aortic valve leaflets were placed in culture medium to induce calcium nodule formation and valve interstitial cells (VICs) cultured from explanted rat valve leaflets were placed on collagen polyacrylamide (PAAM) gels of varying stiffness. The Second Harmonic Generation (SHG) signal and two-photon excited fluorescence (TPEF) generated by the collagen and calcium nodules, respectively, demonstrated that collagen fiber organization decreases with disease progression. Finally, using confocal fluorescence imaging, we found that average nodule size increases with substrate stiffness.