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

Abstract

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.

Stereo Coverage and Overall Stiffness of Biomaterial Arrays Underly Parts of Topography Effects on Cell Adhesion

“…We employed the mold casting method to fabricate the patterned surfaces, as schematically presented in Figure S2, and the topography was controlled with varied array parameters, in particular, heights and diameters. Here, we choose PLLA as the raw material because PLLA as well as its copolymer such as poly­(lactide- co -glycolide) (PLGA) is a kind of polymeric biomaterials widely used in biodegradable implants, − and we choose human umbilical vein endothelial cells (HUVECs) as the model cell type because this is an important cell type widely used in biomaterial studies, in particular for cardiovascular systems. − Roughness, plateau coverage, stereo coverage, and overall stiffness were calculated and correlated to adhesion behaviors of cells on different micropatterns. It is verified that these important parameters can semi-quantify the effects of surface topography on cell adhesion.…”

Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation

“…PEGDA currently provides the best spatial resolution of all biocompatible photo-crosslinkable hydrogels, however, it does not promote cell attachment and alone is not suitable as a matrix for tissue engineering applications. GelMA offers slightly lower resolution, but its high capacity for cell adhesion has resulted in successful DLP and SLA printing of corneal stroma ( Mahdavi et al, 2020 ), cartilage ( Lam et al, 2019 ), and vasculature ( Tomov et al, 2021 ).…”

4D Printing Applications in the Development of Smart Cardiovascular Implants

“…DLP is a more rapid method with a higher resolution compared to extrusion printing which can be used to fabricate precise structures of vessels such as bifurcations. For example, the DLP (Lumen X) printer showed a 74% success rate to fabricate bifurcations while the success rate was 60% for the extrusion approach ( Tomov et al, 2021 ). Quantum X bio is another recently developed light-based printing method which is appropriate for cardiovascular applications.…”