Bioengineering A Three-Dimensional Cardiac Left Ventricle
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Abstract
Hypoplastic left heart syndrome (HLHS) is a congenital condition characterized by an underdeveloped left ventricle (LV). The current treatment options are surgery and/or heart transplant. Current tissue engineering strategies focus on graft models. The development of an engineered 3D cardiac LV would provide a therapeutic option to overcome current treatment limitations. A series of five models, to understand the ideal LV platform, fabricate and optimize a bioengineered open ventricle chamber and complete the chamber with a trileaflet valve, were produced in this research. Models were designed to emulate the human neonate LV geometry; molds were used to produce chitosan scaffolds. Functional models were fabricated by culturing rat neonatal primary cardiac cells on the chitosan scaffold. Chitosan was shown to be biocompatible with suitable material properties. An open chamber model was designed and optimized with respect to cellularization efficiency and function, using a novel seeding strategy and bioreactor, respectively; cellularized constructs demonstrated cardiac myocyte biopotential activity with contractions and pressure generation. Trileaflet valves were engineered and fitted into the open chamber to complete the bioengineered ventricle. The outcome of this research is the production of a complete bioengineered 3D cardiac LV.