Abstract

Left ventricle and aortic valve underdevelopment are presentations in the congenital cardiac condition hypoplastic left heart syndrome (HLHS); current clinical treatments involve right ventricle refunctionalization. Cardiac organoid models provide simplified open chambers engineered into a flow loop, to ameliorate ventricle-type function. Complete bioengineered ventricle development presents a significant advancement in cardiac organoids. This study provides the foundation for bioengineered complete ventricle (BECV) fabrication. Bioengineered trileaflet valve (BETV) molds and chitosan scaffolds were developed to emulate human neonate aortic valve geometry. Bioengineered complete ventricle were fabricated by fitting BETV into a bioengineered open ventricle (BEOV); the chamber was cellularized using a two-stage cellularization strategy, and BETV were passively seeded with rat neonatal cardiac fibroblasts and perfusion cultured for 3 days. Average pressure generated ranged from 0.06 to 0.12 mm Hg; average biopotential output was 1.02 mV. Histologic assessment displayed syncytial-type cardiomyocyte aggregates at the BECV chamber surface; BETV displayed randomly oriented, diffusely distributed cardiac fibroblasts. The fabrication of this novel BECV may aid in developing a functional engineered left ventricle for clinical application in HLHS.

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