Toward a neurospheroid niche model: optimizing embedded 3D bioprinting for fabrication of neurospheroid brain-like co-culture constructs.
Toward a neurospheroid niche model: optimizing embedded 3D bioprinting for fabrication of neurospheroid brain-like co-culture constructs.
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DOI：
10.1088/1758-5090/abc1be
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发表时间：
2020-11-10
期刊：
影响因子：
9
通讯作者：
Shin SR
中科院分区：
文献类型：
--
作者：
Li YE;Jodat YA;Samanipour R;Zorzi G;Zhu K;Hirano M;Chang K;Arnaout A;Hassan S;Matharu N;Khademhosseini A;Hoorfar M;Shin SR
为神经发育和疾病研究创建可靠的体外平台的关键一步是复制多细胞三维（3D）脑微环境并捕获模型中的细胞-细胞相互作用。不同类型的细胞自组织成脑球体的能力可以用来研究大脑发育轨迹和疾病的潜在机制。当前在培养皿中生长的3D类器官和类球体模型的挑战是缺乏对细胞定位和多样性的控制。为了克服这一限制，可以使用微加工将神经球体图案化为可定制的3D结构。我们使用嵌入式3D生物打印技术开发了一种3D类脑共培养构建体，作为一种灵活的解决方案，用于组成具有神经球和神经胶质的异质神经群体。具体而言，在类似于神经干细胞龛环境的工程化星形胶质细胞负载支持浴中制造神经球负载的独立3D结构。一种可光交联的生物墨水和一种热愈合支持浴被设计成模拟软组织的机械模量，同时支持在复杂的3D网络内形成自组织神经球体。此外，生物打印的载有神经球的结构表现出分化成神经元细胞的能力。这些类似大脑的共培养物可以为神经系统疾病、神经再生以及药物开发和再利用提供一个可重复的平台。
A crucial step in creating reliable in vitro platforms for neural development and disorder studies is the reproduction of the multicellular three-dimensional (3D) brain microenvironment and the capturing of cell-cell interactions within the model. The power of self-organization of diverse cell types into brain spheroids could be harnessed to study mechanisms underlying brain development trajectory and diseases. A challenge of current 3D organoid and spheroid models grown in petri-dishes is the lack of control over cellular localization and diversity. To overcome this limitation, neural spheroids can be patterned into customizable 3D structures using microfabrication. We developed a 3D brain-like co-culture construct using embedded 3D bioprinting as a flexible solution for composing heterogenous neural populations with neurospheroids and glia. Specifically, neurospheroid-laden free-standing 3D structures were fabricated in an engineered astrocyte-laden support bath resembling a neural stem cell niche environment. A photo-crosslinkable bioink and a thermal-healing supporting bath were engineered to mimic the mechanical modulus of soft tissue while supporting the formation of self-organizing neurospheroids within elaborate 3D networks. Moreover, bioprinted neurospheroid-laden structures exhibited the capability to differentiate into neuronal cells. These brain-like co-cultures could provide a reproducible platform for modeling neurological diseases, neural regeneration, and drug development and repurposing.
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影响因子：
13.6
作者：
Hinton TJ;Jallerat Q;Palchesko RN;Park JH;Grodzicki MS;Shue HJ;Ramadan MH;Hudson AR;Feinberg AW
通讯作者：
Feinberg AW
影响因子：
9.7
作者：
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DOI：
10.1016/j.ijbiomac.2005.01.002
发表时间：
2005-03-01
影响因子：
8.2
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
13.6
作者：
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通讯作者：
Angelini TE