Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip.
Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip.
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DOI：
10.1016/j.biomaterials.2016.09.003
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发表时间：
2016-12
期刊：
影响因子：
14
通讯作者：
Khademhosseini A
中科院分区：
文献类型：
--
作者：
Zhang YS;Arneri A;Bersini S;Shin SR;Zhu K;Goli-Malekabadi Z;Aleman J;Colosi C;Busignani F;Dell'Erba V;Bishop C;Shupe T;Demarchi D;Moretti M;Rasponi M;Dokmeci MR;Atala A;Khademhosseini A
由于天然心肌的层次结构，工程心脏组织和器官模型仍然是一个巨大的挑战。整合血管的需要带来了额外的复杂性，限制了适用于产生整合的心血管类器官的可用方法。在这项工作中，我们提出了一种新的混合策略的基础上3D生物打印，制造内皮化心肌。通过使用我们的复合生物墨水，微纤维水凝胶支架内直接生物打印的内皮细胞逐渐向微纤维的外周迁移，形成一层融合的内皮。与受控的各向异性一起，该3D内皮床然后用心肌细胞接种以产生能够自发和同步收缩的对齐心肌。我们进一步将类器官嵌入到专门设计的微流体灌注生物反应器中，以完成用于心血管毒性评估的内皮化心肌芯片平台。最后，我们证明了这种技术可以转化为诱导多能干细胞来源的人心肌细胞来构建内皮化的人心肌。我们相信，我们通过创新的3D生物打印技术制造的内皮化类器官的方法可能会在再生医学，药物筛选和潜在的疾病建模中找到广泛的应用。
Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling.
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在药物发现的边界，片上的器官。
DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Esch EW;Bahinski A;Huh D
通讯作者：
Huh D
影响因子：
17.1
作者：
Han, Jin;Kim, Bokyoung;Kim, Byung-Soo
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影响因子：
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作者：
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通讯作者：
Radisic, Milica
影响因子：
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作者：
Bartholomä, P;Gorjup, E;Robitzki, A
通讯作者：
Robitzki, A
影响因子：
6.1
作者：
Agarwal A;Goss JA;Cho A;McCain ML;Parker KK
通讯作者：
Parker KK