Microporous cell-laden hydrogels for engineered tissue constructs

Authors

  • Jae Hong Park,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    3. National Nano Fab Center (NNFC), Daejon, Korea
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  • Bong Geun Chung,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    3. Department of Bionano Engineering, Hanyang University, Ansan, Korea
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  • Won Gu Lee,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Jinseok Kim,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    Current affiliation:
    1. Nanobio Center, Korea Institute of Science and Technology (KIST), Korea.
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  • Mark D. Brigham,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Jaesool Shim,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    3. Department of Mechanical Engineering, Yeungnam University, Gyeongsan, Korea
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  • Seunghwan Lee,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Chang Mo Hwang,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Naside Gozde Durmus,

    1. Department of Biomedical Engineering, Boston University, Massachusetts
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  • Utkan Demirci,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Ali Khademhosseini

    Corresponding author
    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    • Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Rm 265, Cambridge, Massachusetts 02139; telephone: 617-768-8395; fax: 617-768-8477.
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  • J.H.P. and B.G.C. designed and performed the experiments, and analyzed the data. W.G.L. fabricated agarose channels and analyzed the data. J.S.K. conceived the methodology for creating micropores and analyzed confocal images. M.B. measured the porosity and characterized mechanical strength. J.S. characterized diffusion coefficient and profiles. S.H.L. synthesized biomaterials, characterized porosity, and analyzed the data. C.H. performed cell experiments and analyzed the data. G.D. created and characterized pores within agarose gels using sucrose mixtures. U.D. helped in analysis of the data. A.K. supervised the work and conceived of the idea. All authors read and wrote the paper.

  • Jae Hong Park and Bong Geun Chung equally contributed to this work.

Abstract

In this article, we describe an approach to generate microporous cell-laden hydrogels for fabricating biomimetic tissue engineered constructs. Micropores at different length scales were fabricated in cell-laden hydrogels by micromolding fluidic channels and leaching sucrose crystals. Microengineered channels were created within cell-laden hydrogel precursors containing agarose solution mixed with sucrose crystals. The rapid cooling of the agarose solution was used to gel the solution and form micropores in place of the sucrose crystals. The sucrose leaching process generated homogeneously distributed micropores within the gels, while enabling the direct immobilization of cells within the gels. We also characterized the physical, mechanical, and biological properties (i.e., microporosity, diffusivity, and cell viability) of cell-laden agarose gels as a function of engineered porosity. The microporosity was controlled from 0% to 40% and the diffusivity of molecules in the porous agarose gels increased as compared to controls. Furthermore, the viability of human hepatic carcinoma cells that were cultured in microporous agarose gels corresponded to the diffusion profile generated away from the microchannels. Based on their enhanced diffusive properties, microporous cell-laden hydrogels containing a microengineered fluidic channel can be a useful tool for generating tissue structures for regenerative medicine and drug discovery applications. Biotechnol. Bioeng. 2010; 106: 138–148. © 2010 Wiley Periodicals, Inc.

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