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Tissue-Engineered Tubular Heart Valves Combining a Novel Precontraction Phase with the Self-Assembly Method

  • The Pursuit of Engineering the Ideal Heart Valve Replacement or Repair
  • Published:
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Abstract

Recently, the tubular shape has been suggested as an effective geometry for tissue-engineered heart valves, allowing easy fabrication, fast implantation, and a minimal crimped footprint from a transcatheter delivery perspective. This simple design is well suited for the self-assembly method, with which the only support for the cells is the extracellular matrix they produce, allowing the tissue to be completely free from exogenous materials during its entire fabrication process. Tubular constructs were produced by rolling self-assembled human fibroblast sheets on plastic mandrels. After maturation, the tubes were transferred onto smaller diameter mandrels and allowed to contract freely. This precontraction phase thickened the tissue and prevented further contraction, while improving fusion between the self-assembled layers and aligning the cells circumferentially. When mounted in a pulsed-flow bioreactor, the valves showed good functionality with large leaflets coaptation and opening area. Although physiological aortic flow conditions were not reached, the leaflets could withstand a 1 Hz pulsed flow with a 300 mL/s peak flow rate and a 70 mmHg peak transvalvular pressure. This study shows that the self-assembly method, which has already proven its potential for the production of small diameter vascular grafts, could also be used to achieve functional tubular heart valves.

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Acknowledgments

This research was funded by the Fonds de recherche du Québec—Nature et technologies (FRQNT), the Fonds de Recherche du Québec—Santé (FRQS) and ThéCell Network: Réseau de thérapie cellulaire et tissulaire du FRQS, the Canadian Institute for Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC). M.P.D. and C.T. were the recipients of scholarships from the NSERC and worked under the direction of J.R. and F.A.A. The authors would also like to thank Véronique Laterreur, Dan Lacroix, Cindy Perron and Maxime Tondreau for their generous time and knowledge contributions on tissue engineering and Marc-André Plourde-Campagna, Jean-Claude Gariépy and Pierre Carrier for their essential technical assistance on mechanical design and fabrication.

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Authors and Affiliations

  1. Département de génie mécanique, Faculté des sciences et de génie, Université Laval, Pavillon Adrien-Pouliot, 1065, av. de la Médecine, local 1504, Québec, QC, G1V 0A6, Canada

    Maxime Picard-Deland, Jean Ruel & Catherine Tremblay

  2. Centre de recherche en organogénèse expérimentale/LOEX, CMDGT/LOEX Aile-R, Centre de recherche du CHU de Québec, Université Laval, Hôpital Enfant-Jésus, 1401, 18e rue, Québec, QC, G1J 1Z4, Canada

    Maxime Picard-Deland, Todd Galbraith, Catherine Tremblay, Fabien Kawecki, Lucie Germain & François A. Auger

  3. Département de chirurgie, Faculté de médecine, Université Laval, Pavillon Ferdinand-Vandry, 1050, ave de la Médecine, bureau 4633, Québec, QC, G1V 0A6, Canada

    Fabien Kawecki, Lucie Germain & François A. Auger

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  1. Maxime Picard-Deland
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  2. Jean Ruel
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Correspondence to Jean Ruel.

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Associate Editor Lakshmi Prasad Dasi oversaw the review of this article.

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Picard-Deland, M., Ruel, J., Galbraith, T. et al. Tissue-Engineered Tubular Heart Valves Combining a Novel Precontraction Phase with the Self-Assembly Method. Ann Biomed Eng 45, 427–438 (2017). https://doi.org/10.1007/s10439-016-1708-1

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