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用于药物毒性分析的生物打印三维血管化组织模型。

Bioprinted 3D vascularized tissue model for drug toxicity analysis.

作者信息

Massa Solange, Sakr Mahmoud Ahmed, Seo Jungmok, Bandaru Praveen, Arneri Andrea, Bersini Simone, Zare-Eelanjegh Elaheh, Jalilian Elmira, Cha Byung-Hyun, Antona Silvia, Enrico Alessandro, Gao Yuan, Hassan Shabir, Acevedo Juan Pablo, Dokmeci Mehmet R, Zhang Yu Shrike, Khademhosseini Ali, Shin Su Ryon

机构信息

Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Laboratory of Nano-Regenerative Medicine, Facultad de Medicina, Universidad de los Andes, Santiago 7620001, Chile.

出版信息

Biomicrofluidics. 2017 Aug 1;11(4):044109. doi: 10.1063/1.4994708. eCollection 2017 Jul.

Abstract

To develop biomimetic three-dimensional (3D) tissue constructs for drug screening and biological studies, engineered blood vessels should be integrated into the constructs to mimic the drug administration process . The development of perfusable vascularized 3D tissue constructs for studying the drug administration process through an engineered endothelial layer remains an area of intensive research. Here, we report the development of a simple 3D vascularized liver tissue model to study drug toxicity through the incorporation of an engineered endothelial layer. Using a sacrificial bioprinting technique, a hollow microchannel was successfully fabricated in the 3D liver tissue construct created with HepG2/C3A cells encapsulated in a gelatin methacryloyl hydrogel. After seeding human umbilical vein endothelial cells (HUVECs) into the microchannel, we obtained a vascularized tissue construct containing a uniformly coated HUVEC layer within the hollow microchannel. The inclusion of the HUVEC layer into the scaffold resulted in delayed permeability of biomolecules into the 3D liver construct. In addition, the vascularized construct containing the HUVEC layer showed an increased viability of the HepG2/C3A cells within the 3D scaffold compared to that of the 3D liver constructs without the HUVEC layer, demonstrating a protective role of the introduced endothelial cell layer. The 3D vascularized liver model presented in this study is anticipated to provide a better and more accurate liver model system for future drug toxicity testing.

摘要

为了开发用于药物筛选和生物学研究的仿生三维(3D)组织构建体,应将工程化血管整合到构建体中以模拟药物给药过程。通过工程化内皮细胞层来研究药物给药过程的可灌注血管化3D组织构建体的开发仍然是一个深入研究的领域。在此,我们报告了一种简单的3D血管化肝组织模型的开发,该模型通过整合工程化内皮细胞层来研究药物毒性。使用牺牲性生物打印技术,在由包裹在甲基丙烯酰化明胶水凝胶中的HepG2/C3A细胞创建的3D肝组织构建体中成功制造了一个中空微通道。将人脐静脉内皮细胞(HUVECs)接种到微通道中后,我们获得了一个血管化组织构建体,其在中空微通道内包含均匀包被的HUVEC层。将HUVEC层包含在支架中导致生物分子向3D肝构建体的渗透延迟。此外,与没有HUVEC层的3D肝构建体相比,包含HUVEC层的血管化构建体在3D支架内显示出HepG2/C3A细胞的活力增加,证明了引入的内皮细胞层的保护作用。本研究中提出的3D血管化肝模型有望为未来的药物毒性测试提供一个更好、更准确的肝模型系统。

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