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Towards the fabrication of artificial 3D microdevices for neural cell networks

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Abstract

This work reports first steps towards the development of artificial neural stem cell microenvironments for the control and assessment of neural stem cell behaviour. Stem cells have been shown to be found in specific, supportive microenvironments (niches) and are believed to play an important role in tissue regeneration mechanisms. These environments are intricate spaces with chemical and biological features. Here we present work towards the development of physically defined microdevices in which neural and neural stem cells can be studied in 3-dimensions. We have approached this challenge by creating bespoke, microstructured polymer environments using both 2-photon polymerisation and soft lithography techniques. Specifically, we have designed and fabricated biodegradable microwell-shaped devices using an in house synthetized polymer (4-arm photocurable poly-lactid acid) on a bespoke 2-photon polymerisation (2PP) set-up. We have studied swelling and degradation of the constructs as well as biocompatibility. Moreover, we have explored the potential of these constructs as artificial neural cell substrates by culturing NG108-15 cells (mouse neuroblastoma; rat glioma hybrid) and human neural progenitor cells on the microstructures. Finally, we have studied the effects of our artificial microenvironments upon neurite length and cell density.

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Acknowledgments

FC thanks EPSRC for funding under the DTA studentship scheme (for AAG). We are particularly grateful to Nicola Green for her support in confocal imaging.

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    Authors and Affiliations

    1. Biomaterials and Tissue Engineering Group, Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Broad Lane, S3 7HQ, Sheffield, UK

      Andrew A. Gill & Frederik Claeyssens

    2. Bioengineering and Health Technologies Group, The School of Clinical Dentistry, University of Sheffield Claremont Crescent, S10 2 TA, Sheffield, UK

      Ílida Ortega

    3. New Jersey Neuroscience Institute at JFK Medical Center, 65 James Street, Edison, New Jersey, USA

      Stephen Kelly

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    1. Andrew A. Gill
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    2. Ílida Ortega
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    3. Stephen Kelly
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    4. Frederik Claeyssens
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    Correspondence to Ílida Ortega or Frederik Claeyssens.

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    Andrew and Ilida are joint first authors.

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    Gill, A.A., Ortega, Í., Kelly, S. et al. Towards the fabrication of artificial 3D microdevices for neural cell networks. Biomed Microdevices 17, 27 (2015). https://doi.org/10.1007/s10544-015-9929-x

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    • DOI: https://doi.org/10.1007/s10544-015-9929-x

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