Abstract 550: Magnetic Nanoparticle-mediated Targeting Of Endothelium To Address Restenosis In A Bioprinted In Vitro Model Of Pulmonary Arteries
Abstract 550: Magnetic Nanoparticle-mediated Targeting Of Endothelium To Address Restenosis In A Bioprinted In Vitro Model Of Pulmonary Arteries
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摘要 550：磁性纳米颗粒介导的内皮靶向解决肺动脉生物打印体外模型中的再狭窄问题
DOI：
10.1161/atvb.42.suppl_1.550
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Serpooshan, Vahid
中科院分区：
文献类型：
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作者：
Ning, Liqun;Tomov, Martin L;Zanella, Stefano;Zambrano, Byron;Avazmohammadi, Reza;Mahmoudi, Morteza;Bauser-Heaton, Holly;Serpooshan, Vahid
血管再狭窄是再通动脉的主要并发症。纳米颗粒（NP）作为递送系统在推进治疗此类血管异常的策略中显示出巨大的前景。通过实现精确的靶向，纳米粒子可以克服低药效和脱靶效应的挑战。在这里，我们提出了一个由3D生物打印，纳米材料和灌注技术组成的仿生体外平台，以研究NP靶向解决内皮过度生长的用途。我们以高保真度生物打印了3D血管通道，使用明胶甲基丙烯酸酯作为生物墨水，具有动脉般的硬度。使用人内皮细胞（EC）使打印的通道内皮化。GFP标记的超顺磁性氧化铁纳米粒（SPION），负载雷帕霉素抗增殖药物，以生理速率灌注通过分叉动脉模型。计算模型预测了导管与动脉交界处的壁面切应力的最大变化水平，确定了该区域易于再狭窄。在打印的组织中嵌入钕圆盘磁铁以吸引治疗性SPION到高危区域。体外动态培养2周。我们使用AlamarBlue和免疫组织化学评估细胞活力、增殖和功能。结果显示NP递送在减少EC过度生长中的显著靶向作用。该平台能够设计精确的靶向治疗剂，以在高度的空间和时间控制下治疗各种心血管疾病。
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 biomimeticin vitroplatform 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 theRapamuneanti-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 vitrodynamic 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.