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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.

SUBMITTER: Tomov ML

PROVIDER: S-EPMC8823098 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Tomov Martin L ML Perez Lilanni L Ning Liqun L Chen Huang H Jing Bowen B Mingee Andrew A Ibrahim Sahar S Theus Andrea S AS Kabboul Gabriella G Do Katherine K Bhamidipati Sai Raviteja SR Fischbach Jordan J McCoy Kevin K Zambrano Byron A BA Zhang Jianyi J Avazmohammadi Reza R Mantalaris Athanasios A Lindsey Brooks D BD Frakes David D Dasi Lakshmi Prasad LP Serpooshan Vahid V Bauser-Heaton Holly H

Advanced healthcare materials 20210808 20

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 anast ...[more]

PMID: 34369107

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Project description:Background Tetralogy of Fallot with major aortopulmonary collateral arteries is a heterogeneous form of pulmonary artery (PA) stenosis that requires multiple forms of intervention. We present a patient-specific in vitro platform capable of sustained flow that can be used to train proceduralists and surgical teams in current interventions, as well as in developing novel therapeutic approaches to treat various vascular anomalies. Our objective is to develop an in vitro model of PA stenosis based on patient data that can be used as an in vitro phantom to model cardiovascular disease and explore potential interventions. Methods and Results From patient-specific scans obtained via computer tomography or 3-dimensional (3D) rotational angiography, we generated digital 3D models of the arteries. Subsequently, in vitro models of tetralogy of Fallot with major aortopulmonary collateral arteries were first 3D printed using biocompatible resins and next bioprinted using gelatin methacrylate hydrogel to simulate neonatal vasculature or second-order branches of an older patient with tetralogy of Fallot with major aortopulmonary collateral arteries. Printed models were used to study creation of extraluminal connection between an atretic PA and a major aortopulmonary collateral artery using a catheter-based interventional method. Following the recanalization, engineered PA constructs were perfused and flow was visualized using contrast agents and x-ray angiography. Further, computational fluid dynamics modeling was used to analyze flow in the recanalized model. Conclusions New 3D-printed and computational fluid dynamics models for vascular atresia were successfully created. We demonstrated the unique capability of a printed model to develop a novel technique for establishing blood flow in atretic vessels using clinical imaging, together with 3D bioprinting-based tissue engineering techniques. Additive biomanufacturing technologies can enable fabrication of functional vascular phantoms to model PA stenosis conditions that can help develop novel clinical applications.

Dataset Information

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

Publications

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

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