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Biomechanics and Modeling in Mechanobiology

, Volume 11, Issue 7, pp 1015–1027 | Cite as

Passive and active contributions to generated force and retraction in heart valve tissue engineering

  • Marijke A. A. van VlimmerenEmail author
  • Anita Driessen-Mol
  • Cees W. J. Oomens
  • Frank P. T. Baaijens
Open Access
Original Paper

Abstract

In tissue engineered heart valves, cell-mediated stress development during culture results in leaflet retraction at time of implantation. This tissue retraction is partly active due to traction forces exerted by the cells and partly passive due to release of residual stress in the extracellular matrix and the cells. Within this study, we unraveled the passive and active contributions of cells and matrix to generated force and retraction in engineered heart valve tissues. Tissue engineered rectangular strips, fabricated from PGA/P4HB scaffolds and seeded with human myofibroblasts, were cultured for 4 weeks, after which the cellular contribution was changed at different levels. Elimination of the active cellular traction forces was achieved with Cytochalasin D and inhibition of the Rho-associated kinase pathway. Both active and passive cellular contributions were eliminated by lysation and/or decellularization of the tissue. Maximum cell activity was reached by increasing the fetal bovine serum concentration to 50%. The generated force decreased ~20% after elimination of the active cellular component, ~25% when the passive cellular component was removed as well and remained unaffected by increased serum concentrations. Passive retraction accounted for ~60% of total retraction, of which ~15% was residual stress in the matrix and ~45% was passive cell retraction. Cell traction forces accounted for the remainder ~40% of the retraction. Full activation of the cells increased retraction by ~45%. These results illustrate the importance of the cells in the process of tissue retraction, not only actively retracting the tissue, but also in a passive manner to a large extent.

Keywords

Heart valve tissue engineering Stress generation Passive and active retraction Extracellular matrix Myofibroblasts 

Notes

Acknowledgments

The authors gratefully acknowledge the support of the Smart Mix Program of the Netherlands Ministry of Economic Affairs and theNetherlands Ministry of Education, Culture and Science. The authors would like to thank Nicky de Jonge for the visualization of the actin staining and Linda Kock for performing the biochemical assays.

Open Access

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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Copyright information

© The Author(s) 2012

Authors and Affiliations

  • Marijke A. A. van Vlimmeren
    • 1
    Email author
  • Anita Driessen-Mol
    • 2
  • Cees W. J. Oomens
    • 3
  • Frank P. T. Baaijens
    • 4
  1. 1.Department of Biomedical Engineering, WH4.12Eindhoven University of TechnologyEindhovenThe Netherlands
  2. 2.Department Biomedical Engineering, WH4.111Eindhoven University of TechnologyEindhovenThe Netherlands
  3. 3.Department Biomedical Engineering, WH4.124Eindhoven University of TechnologyEindhovenThe Netherlands
  4. 4.Department Biomedical Engineering, WH4.137Eindhoven University of TechnologyEindhovenThe Netherlands

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