Pulmonary vein stenosis (PVS) is an acute pediatric cardiovascular disease that is always lethal if not treated early. While current clinical interventions (stenting and angioplasties) have shown promising results in treating PVS, they require multiple re-interventions that can lead to re-stenosis and diminished long-term efficacy. Thus, there is an
unmet need
to develop functional
in vitro
models of PVS that can serve as a platform to study clinical interventions.
Patient-inspired 3D bioprinted tissue models
provide a unique model to recapitulate and analyze the complex tissue microenvironment impacted by PVS. Here, we developed perfusable
in vitro
models of healthy and stenotic pulmonary vein by 3D reconstruction and bioprinting inspired by patient CT data (
Figure 1
). Models were seeded with human endothelial (ECs) and smooth muscle cells (SMCs) to form a bilayer structure and perfused using a bioreactor to study cell response to stenotic geometry, and to the stent-based treatment. Flow hemodynamics through printed veins were quantified via Computational Fluid Dynamics (CFD) modeling, 4D MRI and 3D Ultrasound Particle Imaging Velocimetry (echo PIV). Cell growth and endothelialization were analyzed. Our work demonstrates the feasibility of bioprinting various cardiovascular cells, to create perfusable, patient-specific vascular constructs that mimic complex
in vivo
geometries. Deeper understanding of EC-SMC crosstalk mechanisms in
in vitro
biomimetic models that incorporate tissue-like geometrical, chemical, and biomechanical ques could offer substantial insights for prevention and treatment of PVS, as well as other cardiovascular disease.
Characterization of Post‐Translational Modifications Related to Cardiovascular Disease