A 3D Bioprinted In Vitro Model of Pulmonary Artery Atresia to Evaluate Endothelial Cell Response to Microenvironment

Vascular atresia are often treated via transcatheter recanalization or surgical vascular anastomosis due to congenital malformations or coronary occlusions. The cellular response to vascular anastomosis or recanalization is, however, largely unknown and current techniques rely on restoration rather than optimization of flow into the atretic arteries. An improved understanding of cellular response post anastomosis may result in reduced restenosis. Here, an in vitro platform is used to model anastomosis in pulmonary arteries (PAs) and for procedural planning to reduce vascular restenosis. Bifurcated PAs are bioprinted within 3D hydrogel constructs to simulate a reestablished intervascular connection. The PA models are seeded with human endothelial cells and perfused at physiological flow rate to form endothelium. Particle image velocimetry and computational fluid dynamics modeling show close agreement in quantifying flow velocity and wall shear stress within the bioprinted arteries. These data are used to identify regions with greatest levels of shear stress alterations, prone to stenosis. Vascular geometry and flow hemodynamics significantly affect endothelial cell viability, proliferation, alignment, microcapillary formation, and metabolic bioprofiles. These integrated in vitro–in silico methods establish a unique platform to study complex cardiovascular diseases and can lead to direct clinical improvements in surgical planning for diseases of disturbed flow.

Statement of significance

Soft materials with electrical conductivity are investigated for healthcare applications, such as electrodes to measure vital signs that can easily adapt to the shape and the movements of human skin. Conductive hydrogels (i.e. gels containing water) are ideal materials for this purpose due softness and flexibility. In this this work, we report hydrogels obtained mixing an electrically conductive polymer, a water-soluble biocompatible polymer and a salt. These materials show high adhesion on skin, electrical conductivity and ability to self-repair after a mechanical damage. These hydrogels were successfully used to fabricate electrode to measure cardiac and muscular electrical signals.