Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds


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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY license ( Funding: This study was supported by funding from the Biotechnology and Biological Sciences Research Council (BB/H008527/1) ( uk), China Regenerative Medicine International (CRMI), Jiangsu In-dustrial Technology Research Institute (JITRI), and Engineering and Physical Sciences Research Council (EPSRC EP/P005381/1 and EP/ V007785/1).
Uncontrolled Keywords: Microgel,Hydrogel,Hyaluronan,iPSC,Neural tissue engineering,3D printing
Publication ISSN: 2452-199X
Last Modified: 28 May 2024 07:25
Date Deposited: 15 Jul 2021 09:36
Full Text Link:
Related URLs: https://linking ... 452199X21003418 (Publisher URL)
PURE Output Type: Article
Published Date: 2022-03
Published Online Date: 2021-07-15
Accepted Date: 2021-07-07
Authors: Hsu, Chia-chen
George, Julian H.
Waller, Sharlayne
Besnard, Cyril
Nagel, David A (ORCID Profile 0000-0002-9055-1775)
Hill, Eric J (ORCID Profile 0000-0002-9419-1500)
Coleman, Michael D. (ORCID Profile 0000-0002-5510-6852)
Korsunsky, Alexander M.
Cui, Zhanfeng
Ye, Hua

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