期刊
BIOFABRICATION
卷 13, 期 1, 页码 -出版社
IOP PUBLISHING LTD
DOI: 10.1088/1758-5090/abc1be
关键词
embedded bioprinting; neural stem cells; astrocytes; neurospheroids; thermal-healing hydrogels; brain tissues
资金
- National Institutes of Health [R01AR074234, R21EB026824, EB021857, AR073135, AR074234, UG3TR003148, GM126571]
- Gillian Reny Stepping Strong Center for Trauma Innovation
- AHA [19IPLOI34660079]
- Taiwan Bio-Development Foundation, Ministry of Science and Technology, Taiwan [MOST 107-2314-B-035-001-MY2]
- department of Mechanical Engineering at Stevens Institute of Technology
- Natural Sciences and Engineering Research Council of Canada (NSERC)
Researchers have used embedded 3D bioprinting to create structured brain-like co-culture constructs with neurospheroid patterns, mimicking a supportive bed resembling a neural stem cell growth environment. These brain-like co-cultures can provide a reproducible platform for modeling neurological diseases, neural regeneration, and drug development and repurposing.
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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