Modulating and modeling aggregation of cell-seeded microcarriers in stirred culture system for macrotissue engineering.

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  • Author(s): Mei Y;Mei Y; Luo H; Tang Q; Ye Z; Zhou Y; Tan WS
  • Source:
    Journal of biotechnology [J Biotechnol] 2010 Nov; Vol. 150 (3), pp. 438-46. Date of Electronic Publication: 2010 Oct 01.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8411927 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4863 (Electronic) Linking ISSN: 01681656 NLM ISO Abbreviation: J Biotechnol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Science Publishers, c1984-
    • Subject Terms:
      Bioreactors* ; Cell Aggregation* ; Tissue Engineering*/instrumentation ; Tissue Engineering*/methods; Tissue Culture Techniques/*instrumentation; Cells, Cultured ; Fibroblasts ; Humans ; Microscopy, Electron, Scanning ; Reproducibility of Results ; Tissue Scaffolds
    • Abstract:
      A recently developed protocol, "microtissue assembly" holds great promise to address the issue of limited mass transfer within engineered large tissue replacements (macrotissues), wherein small "building blocks" (microtissues) are prepared and then assembled into macrotissues. Previous studies suggested that aggregation behavior of microcarrier-based microtissues were very important for macrotissue engineering. However, a systematic study on the aggregation behavior of microtissues is still missing. In this study, to examine the aggregation behavior of microtissues, effects of key operation parameters in dynamic culture including cell seeding density, microcarrier concentration, L-ascorbic acid 2-phosphate (V(c)) and agitating speed were investigated. The aggregation process could be divided into three phases (i.e., lag, growth and stable). Aggregation efficiency (S) was found to be modulated by cell seeding density, microcarrier concentration, addition of V(c) and agitating speed. A mathematical model correlating the operation parameters with S at different phases of aggregation was developed and experimentally proved to be able to predict S with varied operation parameters. In the end, a cylindrical macrotissue (diameter × height: 2.0 cm × 0.8 cm) with fairly good integrity and cellularity and uniform cell distribution was successfully engineered through perfusion assembling microtissues with controlled S under selected culture conditions. Our study showed that aggregation of microtissues could be precisely modulated, which would definitely facilitate engineering macrotissues with high quality.
      (Copyright © 2010 Elsevier B.V. All rights reserved.)
    • Publication Date:
      Date Created: 20101005 Date Completed: 20110303 Latest Revision: 20101115
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.jbiotec.2010.09.953
    • Accession Number:
      20888876