Targeted Rapamycin Delivery via Magnetic Nanoparticles to Address Stenosis in a 3D Bioprinted in Vitro Model of Pulmonary Veins.
Liqun NingStefano ZanellaMartin L TomovMehdi Salar AmoliLinqi JinBoeun HwangMaher SaadehHuang ChenSunder NeelakantanLakshmi Prasad DasiReza AvazmohammadiMorteza MahmoudiHolly D Bauser-HeatonVahid SerpooshanPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
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.
Keyphrases
- pulmonary hypertension
- iron oxide nanoparticles
- cell proliferation
- endothelial cells
- cancer therapy
- single cell
- nitric oxide
- emergency department
- case report
- pulmonary artery
- pulmonary arterial hypertension
- cell therapy
- risk assessment
- wastewater treatment
- risk factors
- heart failure
- climate change
- big data
- inferior vena cava
- mesenchymal stem cells
- bone marrow
- atrial fibrillation
- ultrasound guided
- human health
- pi k akt
- bioinformatics analysis