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Article

Microporous cell-laden hydrogels for engineered tissue constructs†‡

  1. Jae Hong Park1,2,3,
  2. Bong Geun Chung1,2,4,
  3. Won Gu Lee1,2,
  4. Jinseok Kim1,2,§,
  5. Mark D. Brigham1,2,
  6. Jaesool Shim1,2,5,
  7. Seunghwan Lee1,2,
  8. Chang Mo Hwang1,2,
  9. Naside Gozde Durmus6,
  10. Utkan Demirci1,2,
  11. Ali Khademhosseini1,2,*

Article first published online: 20 JAN 2010

DOI: 10.1002/bit.22667

Issue

Biotechnology and Bioengineering

Biotechnology and Bioengineering

Volume 106, Issue 1, pages 138–148, 1 May 2010

Additional Information

How to Cite

Park, J. H., Chung, B. G., Lee, W. G., Kim, J., Brigham, M. D., Shim, J., Lee, S., Hwang, C. M., Durmus, N. G., Demirci, U. and Khademhosseini, A. (2010), Microporous cell-laden hydrogels for engineered tissue constructs. Biotechnol. Bioeng., 106: 138–148. doi: 10.1002/bit.22667

Author Information

  1. 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. 2

    Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

  3. 3

    National Nano Fab Center (NNFC), Daejon, Korea

  4. 4

    Department of Bionano Engineering, Hanyang University, Ansan, Korea

  5. 5

    Department of Mechanical Engineering, Yeungnam University, Gyeongsan, Korea

  6. 6

    Department of Biomedical Engineering, Boston University, Massachusetts

  1. §

    Nanobio Center, Korea Institute of Science and Technology (KIST), Korea.

*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.

  1. †

    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.

  2. ‡

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

Publication History

  1. Issue published online: 19 MAR 2010
  2. Article first published online: 20 JAN 2010
  3. Accepted manuscript online: 20 JAN 2010 12:00AM EST
  4. Manuscript Accepted: 30 DEC 2009
  5. Manuscript Revised: 17 DEC 2009
  6. Manuscript Received: 24 AUG 2009

Funded by

  • The National Institutes of Health. Grant Numbers: DE019024, HL092836, EB007249
  • US Army Core of Engineers
  • The Charles Stark Draper Laboratory
  • Korea Research Foundation Grant (MOEHRD). Grant Number: KRF-2007-357-D00101

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Keywords:

  • microporous;
  • agarose;
  • cell-laden hydrogel;
  • tissue engineering

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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