Journal article
Nanoarchitectonics of a Microsphere-Based Scaffold for Modeling Neurodevelopment and Neurological Disease
ACS applied bio materials, Vol.5(2), pp.528-544
01/19/2022
DOI: 10.1021/acsabm.1c01012
PMCID: PMC8865216
PMID: 35045249
Abstract
Three-dimensional cellular constructs derived from pluripotent stem cells allow the ex vivo study of neurodevelopment and neurological disease within a spatially organized model. However, the robustness and utility of three-dimensional models is impacted by tissue self-organization, size limitations, nutrient supply, and heterogeneity. In this work, we have utilized the principles of nanoarchitectonics to create a multifunctional polymer/bioceramic composite microsphere system for stem cell culture and differentiation in a chemically defined micro-environment. Microspheres could be customized to produce three-dimensional structures of defined size (ranging from 100 to <350 mu m) with lower mechanical properties compared with a thin film. Furthermore, the microspheres softened in solution, approaching more tissue-like mechanical properties over time. With neural stem cells (NSCs) derived from human induced pluripotent stem cells, microsphere-cultured NSCs were able to utilize multiple substrates to promote cell adhesion and proliferation. Prolonged culture of NSC-bound microspheres under differentiating conditions allowed the formation of both neural and glial cell types from control and patient-derived stem cell models. Human NSCs and differentiated neurons could also be cocultured with astrocytes and human umbilical vein endothelial cells, demonstrating application for tissue-engineered modeling of development and human disease. We further demonstrated that microspheres allow the loading and sustained release of multiple recombinant proteins to support cellular maintenance and differentiation. While previous work has principally utilized self-organizing models or protein-rich hydrogels for neural culture, the three-dimensional matrix developed here through nanoarchitectonics represents a chemically defined and robust alternative for the in vitro study of neurodevelopment and nervous system disorders.
Details
- Title: Subtitle
- Nanoarchitectonics of a Microsphere-Based Scaffold for Modeling Neurodevelopment and Neurological Disease
- Creators
- Eric S. Sandhurst - University of South DakotaSharad Jaswandkar - North Dakota State UniversityKrishna Kundu - North Dakota State UniversityDinesh R. Katti - North Dakota State UniversityKalpana S. Katti - North Dakota State UniversityHongli Sun - University of South DakotaDaniel Engebretson - University of South DakotaKevin R. Francis - University of South Dakota
- Resource Type
- Journal article
- Publication Details
- ACS applied bio materials, Vol.5(2), pp.528-544
- DOI
- 10.1021/acsabm.1c01012
- PMID
- 35045249
- PMCID
- PMC8865216
- NLM abbreviation
- ACS Appl Bio Mater
- ISSN
- 2576-6422
- eISSN
- 2576-6422
- Publisher
- Amer Chemical Soc
- Number of pages
- 17
- Grant note
- DGE-1633213 / National Science Foundation (NSF) State of South Dakota IIA-1355423; OIA-1946202 / NSF/EPSCoR Cooperative Agreements NIGMS P20 GM103620; P20 GM103548 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/19/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery
- Record Identifier
- 9984367727902771
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