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Cyclic Stretch and Perfusion Bioreactor for Conditioning Large Diameter Engineered Tissue Tubes

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Abstract

A cyclic stretch and perfusion bioreactor was designed to culture large diameter engineered tissue tubes for heart valve applications. In this bioreactor, tubular tissues consisting of dermal fibroblasts in a sacrificial fibrin gel scaffold were placed over porated latex support sleeves and mounted in a custom bioreactor. Pulsatile flow of culture medium into the system resulted in cyclic stretching as well as ablumenal, lumenal, and transmural flow (perfusion). In this study, lumenal remodeling, composition, and mechanical strength and stiffness were compared for tissues cyclically stretched in this bioreactor on either the porated latex sleeves or solid latex sleeves, which did not permit lumenal or transmural flow. Tissues cyclically stretched on porated sleeves had regions of increased lumenal remodeling and cellularity that were localized to the columns of pores in the latex sleeve. A CFD model was developed with COMSOL Multiphysics® to predict flow of culture medium in and around the tissue, and the predictions suggest that the enhanced lumenal remodeling was likely a result of elevated shear stresses and transmural velocity in these regions. This work highlights the beneficial effects of increased nutrient transport and flow stimulation for accelerating in vitro tissue remodeling.

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Abbreviations

CFD:

Computational fluid dynamics

Pe:

Peclet number

TEHV:

Tissue-engineered heart valve

UTS:

Ultimate tensile strength

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Acknowledgments

The authors thank Alex Weston, Naomi Ferguson, Sandra Johnson, Susan Saunders, Jay Reimer, and Zeeshan Syedain for technical assistance and the University of Minnesota Supercomputing Institute for computing resources. This study was funded by an NSF Graduate Research Fellowship (J.B.S.) and NIH R01 HL107572 (R.T.T.).

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Authors and Affiliations

  1. Department of Chemical Engineering & Materials Science, University of Minnesota, Minneapolis, MN, USA

    Jillian B. Schmidt & Robert T. Tranquillo

  2. Department of Biomedical Engineering, University of Minnesota, 7-114 Nils Hasselmo Hall, 312 Church St. SE, Minneapolis, MN, 55455, USA

    Robert T. Tranquillo

Authors
  1. Jillian B. Schmidt
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Correspondence to Robert T. Tranquillo.

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Associate Editor Kent Leach oversaw the review of this article.

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Schmidt, J.B., Tranquillo, R.T. Cyclic Stretch and Perfusion Bioreactor for Conditioning Large Diameter Engineered Tissue Tubes. Ann Biomed Eng 44, 1785–1797 (2016). https://doi.org/10.1007/s10439-015-1437-x

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  • DOI: https://doi.org/10.1007/s10439-015-1437-x

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