Developing a 3D Bioprinted model of Pulmonary Veins to investigate altered endothelial cell signaling in Hypoxia
Author(s)
Parab, Manasvi
Advisor(s)
Bauser-Heaton, Holly
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Abstract
Pulmonary Vein Stenosis (PVS) is an acute cardiovascular condition characterized by progressive lumen size reduction due to overgrowth of connective and fibrotic tissue in one or more of the pulmonary veins. PVS often occurs in premature infants, particularly those with bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from prolonged oxygen exposure and mechanical ventilation. Current literature suggests that the same inflammatory and vascular injury mechanisms contributing to BPD may also predispose infants to PVS. Intermittent hypoxemia – recurrent episodes of low oxygen saturation and bradycardia – play a major role in the PVS pathophysiology, especially in preterm neonates. Sustained hypoxic episodes can further result in lung tissue damage, inflammation, impairment of the vasculature, and hence can exacerbate both BPD and PVS. Understanding the role of hypoxia in the evolution of these diseases is essential for early diagnosis and the development of preventive and therapeutic strategies to improve outcomes in this high-risk population. We thus hypothesize that patient-inspired 3D bioprinted tissue models can provide a unique approach to recapitulate changing pO2 levels, can allow for analysis of the complex tissue microenvironment impacted during PVS. Our central hypothesis is that aberrant endothelial cell-cell interactions are responsible for stenosis and are further exacerbated by local hypoxemia through dysregulated HIF signaling. To address these challenges, we have developed a high-throughput, perfusable three-dimensional (3D), bioprinted in-vitro model of pulmonary vein, with the ability to tune the microenviroment and pO2 levels of the vasculature. Our objective is to identify aberrations in the hypoxia-induced (HIF) and potentially VEGF signaling pathways in PVS that may offer strategic insights into patient-specific mechanisms and treatment.
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Date
2025-04-30
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