Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells
Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells
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DOI：
10.1002/adhm.201600095
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发表时间：
2016-06-22
影响因子：
10
通讯作者：
Crook, Jeremy M.
中科院分区：
文献类型：
--
作者：
Gu, Qi;Tomaskovic-Crook, Eva;Crook, Jeremy M.
生物材料中干细胞的直写打印为体外建模和再生医学的组织工程提供了机会。在这里，报道了通过打印原位分化为功能性神经元和支持神经胶质的人类神经干细胞来构建神经组织的第一个例子。所述支持生物材料包含新型临床相关的基于多糖的生物墨水，所述生物墨水包含藻酸盐、羧甲基壳聚糖和琼脂糖。打印的生物墨水通过稳定的交联快速凝胶化，形成多孔3D支架，封装干细胞，用于原位扩增和分化。分化的神经元形成突触接触，建立网络，是自发活动的，显示荷包牡丹碱诱导的钙反应增加，并主要是γ-氨基丁酸表达。3D组织将有助于人类神经发育，功能和疾病的研究，并可适用于从不同干细胞类型工程其他3D组织。
Direct-write printing of stem cells within biomaterials presents an opportunity to engineer tissue for in vitro modeling and regenerative medicine. Here, a first example of constructing neural tissue by printing human neural stem cells that are differentiated in situ to functional neurons and supporting neuroglia is reported. The supporting biomaterial incorporates a novel clinically relevant polysaccharide-based bioink comprising alginate, carboxymethyl-chitosan, and agarose. The printed bioink rapidly gels by stable cross-linking to form a porous 3D scaffold encapsulating stem cells for in situ expansion and differentiation. Differentiated neurons form synaptic contacts, establish networks, are spontaneously active, show a bicuculline-induced increased calcium response, and are predominantly gamma-aminobutyric acid expressing. The 3D tissues will facilitate investigation of human neural development, function, and disease, and may be adaptable for engineering other 3D tissues from different stem cell types.