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Vascular restenosis is a major complication in recanalized arteries. Nanoparticles (NPs) have shown great promise as delivery systems in advancing strategies to treat such vascular anomalies. By enabling precise targeting, NPs can overcome the challenges of low drug efficacy and off-target effects. Here we present a biomimetic in vitro platform comprised of 3D bioprinting, nanomaterials, and perfusion technologies, to study the use of NP targeting to address endothelial overgrowth. We bioprinted 3D vascular channels at high fidelity, using gelatin methacrylate as bioink, with artery-like stiffness. Human endothelial cells (ECs) were used to endothelialize the printed channels. GFP-labelled superparamagnetic iron oxide NPs (SPIONs), loaded with the Rapamune anti-proliferative drug, were perfused through the bifurcated artery model at physiological rate. Computational modeling predicted greatest level of alterations in wall shear stress in the conduit’s junction with the artery, identifying this region prone to restenosis. A neodymium disc magnet was embedded in the printed tissue to attract the therapeutic SPIONs to the region of high risk. In vitro dynamic culture was conducted for 2 wks. We assessed cell viability, proliferation, and function using AlamarBlue and immunohistochemistry. Results showed significant targeted effect of NP delivery in reducing EC overgrowth. This platform enables design of precise targeting of therapeutics to treat a variety of cardiovascular diseases at a high spatial and temporal control.more » « less
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Tomov, Martin L.; Perez, Lilanni; Ning, Liqun; Chen, Huang; Jing, Bowen; Mingee, Andrew; Ibrahim, Sahar; Theus, Andrea S.; Kabboul, Gabriella; Do, Katherine; et al (, Advanced Healthcare Materials)
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