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InVERT molding for scalable control of tissue microarchitecture

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Author(s)
Ungrin, M. D.
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Chaturvedi, R. R.
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Zandstra, P. W.
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Chen, C. S.
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Stevens, Kelly R.
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Ng, Shengyong
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Christine, Kathleen
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Li, Cheri Yingjie
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Carvalho, Brian
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Schwartz, Robert E.
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Date Issued
May 2013
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Stevens, K. R., M. D. Ungrin, R. E. Schwartz, S. Ng, B. Carvalho, K. S. Christine, R. R. Chaturvedi, et al. “InVERT Molding for Scalable Control of Tissue Microarchitecture.” Nature Communications 4 (May 14, 2013): 1847.
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Author's final manuscript
Abstract
Complex tissues contain multiple cell types that are hierarchically organized within morphologically and functionally distinct compartments. Construction of engineered tissues with optimized tissue architecture has been limited by tissue fabrication techniques, which do not enable versatile microscale organization of multiple cell types in tissues of size adequate for physiological studies and tissue therapies. Here we present an ‘Intaglio-Void/Embed-Relief Topographic molding’ method for microscale organization of many cell types, including induced pluripotent stem cell-derived progeny, within a variety of synthetic and natural extracellular matrices and across tissues of sizes appropriate for in vitro, pre-clinical, and clinical studies. We demonstrate that compartmental placement of non-parenchymal cells relative to primary or induced pluripotent stem cell-derived hepatocytes, compartment microstructure, and cellular composition modulate hepatic functions. Configurations found to sustain physiological function in vitro also result in survival and function in mice for at least 4 weeks, demonstrating the importance of architectural optimization before implantation.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
http://hdl.handle.net/1721.1/86113
DOI of Published Version
https://doi.org/10.1038/ncomms2853
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