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VascuTrainer: A Mobile and Disposable Bioreactor System for the Conditioning of Tissue-Engineered Vascular Grafts

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Abstract

In vitro tissue engineering of vascular grafts requires dynamic conditioning in a bioreactor system for in vitro tissue maturation and remodeling to receive a mechanically adequate and hemocompatible implant. The goal of the current work was to develop a bioreactor system for the conditioning of vascular grafts which is (i) able to create a wide range of flow, pressure and frequency conditions, including physiological ones; (ii) compact and easy to assemble; (iii) transportable; (iv) disposable. The system is driven by a small centrifugal pump controlled via a custom-made control unit, which can also be operated on batteries to allow for autonomous transportation. To show the potential of the newly developed bioreactor system small-caliber vascular composite grafts (n = 5, internal diameter = 3 mm, length = 12.5 cm) were fabricated using a fibrin scaffold embedding human umbilical artery smooth muscle cells and a polyvinylidene fluoride warp-knitted macroporous mesh. Subsequently, the vascular grafts were endothelialized and mounted in the bioreactor system for conditioning. The conditioning parameters remained within the predefined range over the complete conditioning period and during operation on batteries as tested for up to 25 h. Fabrication and pre-conditioning under arterial pressure and shear stress conditions resulted in robust and hemocompatible tissue-engineered vascular grafts. Analysis of immunohistochemical stainings against extracellular matrix and cell-specific proteins revealed collagen I and collagen III deposition. The luminal surface was confluently covered with endothelial cells. The developed bioreactor system showed cytocompatibility and pH, pO2, pCO2, glucose and lactate stayed constant. Sterility was maintained during the complete fabrication process of the vascular grafts. The potential of a versatile and mobile system and its functionality by conditioning tissue-engineered vascular grafts under physiological pressure and flow conditions could be demonstrated.

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Acknowledgments

Funded by the Excellence Initiative of the German federal and state governments in the framework of the i3tm Seed Fund projects (Funding Number: SF_16-6-01) and Step2Projects. We thank Dennis Faßbaender, Institute of Applied Medical Engineering, for his valuable contributions to the development of the pump controller.

Conflict of interest

The authors declare that no competing financial or other interests have influenced this study. None of the authors is financially affiliated with any of the companies mentioned.

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Authors and Affiliations

  1. Department of Biohybrid & Medical Textiles (BioTex), AME-Helmholtz Institute for Biomedical Engineering & Institut für Textiltechnik (ITA), RWTH Aachen University, Pauwelsstraße 20, 52074, Aachen, Germany

    Frederic Wolf, Diana M. Rojas González, Stefan Jockenhoevel & Petra Mela

  2. AMIBM-Aachen-Maastricht-Institute for Biobased Materials, Maastricht University, Maastricht, The Netherlands

    Frederic Wolf, Diana M. Rojas González, Stefan Jockenhoevel & Petra Mela

  3. Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Pauwelsstraße 20, 52074, Aachen, Germany

    Ulrich Steinseifer & Thomas Schmitz-Rode

  4. Laboratory of Machine Tools and Production Engineering, Department of Automation & Control, RWTH Aachen University, Steinbachstraße 19, 52074, Aachen, Germany

    Markus Obdenbusch, Werner Herfs & Christian Brecher

Authors
  1. Frederic Wolf
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  2. Diana M. Rojas González
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  3. Ulrich Steinseifer
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  4. Markus Obdenbusch
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  6. Christian Brecher
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  7. Stefan Jockenhoevel
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  8. Petra Mela
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  9. Thomas Schmitz-Rode
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Corresponding author

Correspondence to Petra Mela.

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Associate Editor Peter E. McHugh oversaw the review of this article.

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Wolf, F., Rojas González, D.M., Steinseifer, U. et al. VascuTrainer: A Mobile and Disposable Bioreactor System for the Conditioning of Tissue-Engineered Vascular Grafts. Ann Biomed Eng 46, 616–626 (2018). https://doi.org/10.1007/s10439-018-1977-y

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