Valve interstitial cells under impact load, a mechanobiology study

Abstract

Understanding the relationship between mechanobiology and the biosynthetic activities of the valve interstitial cells (VICs) in health and disease under severe dynamic loading conditions is of particular interest. The purpose of this study is to further understand the mechanobiology of heart valve leaflet tissue and the VICs under impact forces. Two novel computational and experimental platforms were developed to study the effect of impact load on the VICs to monitor for apoptosis. The first objective was to design and develop an apparatus to experimentally study viability (apoptosis) of the porcine heart valve leaflet tissue VICs in the aortic position under controlled impact forces. Apoptosis was assessed based on terminal transferase dUTP nick end-labelling (TUNEL) assay. The second objective was to develop a computational platform to estimate the stress and strain fields in the vicinity of VICs when the tissue experiences impact forces. A nonlinear finite element (FE) model with an anisotropic, hyperelastic and heterogeneous material model for the matrix and cells was developed. Preliminary results confirm that interstitial cells are successfully resistant to impact loads up to 30 times more than normal physiological conditions. Additionally, the structure and composition of heart valve leaflet tissue provides a mechanical shield for VICs protecting them from excessive mechanical forces such as impact loads. Although, the entire tissue may experience excessive stresses, which may lead to structural damage, the stresses around and near VICs remain consistency low. Results of this study may be used for heart valve leaflet tissue-engineering, as well as further understanding the mechanobiology of the VICs in health and disease.