Liqun Ning, Stefano Zanella, Martin M. Tomov, Medhi Salar Amoli, Linqi Jin, Bouen Hwang, Maher Saadeh, Huang Chen, Sunder Neelakantan, Lakshmi Prasad Dasi, Reza Avazmohammadi, Morteza Mahmooudi, Holly D. Bauser-Heaton, Vahid Serpooshan
Emory University School of Medicine, Children’s Healthcare of Atlanta and Georgia Institute of Technology. Cleveland State University. Texas A&M University. Michigan State University.
United States
Advanced Science
Adv Sci 2024;
DOI: 10.1002/advs.202400476
Abstract
Vascular cell overgrowth and lumen size reduction in pulmonary vein stenosis (PVS) can result in elevated PV pressure, pulmonary hypertension, cardiac failure, and death. Administration of chemotherapies such as rapamycin have shown promise by inhibiting the vascular cell proliferation; yet clinical success is limited due to complications such as restenosis and off-target effects. The lack of in vitro models to recapitulate the complex pathophysiology of PVS has hindered the identification of disease mechanisms and therapies. This study integrated 3D bioprinting, functional nanoparticles, and perfusion bioreactors to develop a novel in vitro model of PVS. Bioprinted bifurcated PV constructs are seeded with endothelial cells (ECs) and perfused, demonstrating the formation of a uniform and viable endothelium. Computational modeling identified the bifurcation point at high risk of EC overgrowth. Application of an external magnetic field enabled targeting of the rapamycin-loaded superparamagnetic iron oxide nanoparticles at the bifurcation site, leading to a significant reduction in EC proliferation with no adverse side effects. These results establish a 3D bioprinted in vitro model to study PV homeostasis and diseases, offering the potential for increased throughput, tunability, and patient specificity, to test new or more effective therapies for PVS and other vascular diseases.
Category
Segmental Pulmonary Venous Disease. Without a Focus on Pulmonary Hypertension
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Mechanical and Computer Models of Pulmonary Vascular Disease and Therapy
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes