Characterization of pediatric porcine pulmonary valves as a model for tissue engineered heart valves

Abstract

AbstractHeart valve tissue engineering holds the potential to transform the surgical management of congenital heart defects affecting the pediatric pulmonary valve (PV) by offering a viable valve replacement with the compositional, architectural and mechanical properties required to functionin situ. While aiming to recapitulate the native valve, the minimum requirement for tissue engineered heart valves (TEHVs) has historically been adequate mechanical function at implantation. However, long-termin situfunctionality of TEHVs remains elusive, suggesting that a closer approximation of the native valve is required. The realization of biomimetic engineered pediatric PV is impeded by insufficient characterization of healthy pediatric tissue. In this study, we comprehensively characterized the planar biaxial tensile behaviour, extracellular matrix (ECM) composition and organization, and valvular interstitial cell (VIC) phenotypes of PVs from piglets to provide benchmarks for TEHVs. The piglet PV possessed an anisotropic and non-linear tension-strain profile from which material constants for a predictive constitutive model were derived. Further, the ECM of the pediatric PV possessed a trilayer organization populated by collagen, glycosaminoglycans, and elastin. Biochemical quantification of ECM proteins normalized to wet weight and DNA content of PV tissue revealed homogenous distribution of proteins across sampled regions of the leaflet. Finally, the predominant phenotype of VICs in the piglet PV was quiescent vimentin-expressing fibroblasts, with a small proportion of activated α-smooth muscle actin-expressing myofibroblasts residing primarily at the base of the leaflet. Overall, the properties characterized in this study can be used to inform TEHV design parameters towards generation of biomimetic pediatric PVs.Graphical Abstract