Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds.
Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds.
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DOI：
10.1016/j.bioactmat.2021.07.008
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发表时间：
2022-03
影响因子：
18.9
通讯作者：
Ye H
中科院分区：
文献类型：
--
作者：
Hsu CC;George JH;Waller S;Besnard C;Nagel DA;Hill EJ;Coleman MD;Korsunsky AM;Cui Z;Ye H
为了反映人类的发展，创造一种能够支持细胞长期存活、分化和成熟的基质至关重要。水凝胶是有前途的 3D 培养材料。然而，由致密聚合物网络组成的整体结构通常会导致微环境不佳，阻碍营养物质交换和细胞间相互作用。在此，基于颗粒水凝胶的支架用于支持 3D 人类诱导多能干细胞 (hiPSC) 衍生的神经网络。开发了定制设计的 3D 打印工具集，用于将透明质酸水凝胶挤出多孔尼龙织物以生成水凝胶颗粒。使用较弱的二次凝胶步骤将细胞和水凝胶颗粒组合，形成自支撑的充满细胞的支架。在三天和七天时，与散装水凝胶相比，颗粒支架支持更高的细胞活力，而与散装水凝胶（22.90 ± 4.70 μm）相比，颗粒支架在 7 天后支持更多的神经突承载细胞和更长的神经突延伸（65.52 ± 11.59 μm）。临床相关的 hiPSC 衍生神经细胞在颗粒水凝胶中的长期（三个月）培养支持良好建立的神经元和星形细胞集落以及支架内部和外部的高水平神经突延伸。这种方法很重要，因为它提供了一种简单、快速和有效的方法来在水凝胶培养物中实现组织相关的颗粒结构。在长期培养中，颗粒水凝胶支持神经培养的发展，具有广泛的神经突生长。培养 7 天后，颗粒状水凝胶可显着提高细胞活力和神经突生长。简单的 3D 打印挤出和混合工具集用于生成细胞并将其均匀地接种到颗粒状水凝胶中。为 3D 打印提供工具集设计，支持使用和定制所描述的技术。
To reflect human development, it is critical to create a substrate that can support long-term cell survival, differentiation, and maturation. Hydrogels are promising materials for 3D cultures. However, a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction. Herein, granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell (hiPSC)-derived neural networks. A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules. Cells and hydrogel granules were combined using a weaker secondary gelation step, forming self-supporting cell laden scaffolds. At three and seven days, granular scaffolds supported higher cell viability compared to bulk hydrogels, whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions (65.52 ± 11.59 μm) after seven days compared to bulk hydrogels (22.90 ± 4.70 μm). Long-term (three-month) cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold. This approach is significant as it provides a simple, rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures. In longer-term culture, granular hydrogels supported the development of neural culture with extensive neurite outgrowth. Granular hydrogels supported significantly higher cell viability and neurite outgrowth over 7 days of culture. A simple 3D printed extrusion and mixing toolset is used to generate and homogenously seed cells into granular hydrogels. The toolset designs are provided for 3D printing, enabling use and customization of the techniques described.
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影响因子：
14
作者：
Burdick, JA;Ward, M;Langer, R
通讯作者：
Langer, R
影响因子：
14
作者：
Cheng, Tzu-Yun;Chen, Ming-Hong;Wang, Tzu-Wei
通讯作者：
Wang, Tzu-Wei
DOI：
10.1073/pnas.1202922109
发表时间：
2012-04-10
影响因子：
11.1
作者：
Bilican, Bilada;Serio, Andrea;Chandran, Siddharthan
通讯作者：
Chandran, Siddharthan
可注射的超分子水凝胶/微凝胶复合材料用于治疗性递送。
影响因子：
4.6
作者：
Chen MH;Chung JJ;Mealy JE;Zaman S;Li EC;Arisi MF;Atluri P;Burdick JA
通讯作者：
Burdick JA
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz