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A Dual-Mode Bioreactor System for Tissue Engineered Vascular Models

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Abstract

In the past decades, vascular tissue engineering has made great strides towards bringing engineered vascular tissues to the clinics and, in parallel, obtaining in-lab tools for basic research. Herein, we propose the design of a novel dual-mode bioreactor, useful for the fabrication (construct mode) and in vitro stimulation (culture mode) of collagen-based tubular constructs. Collagen-based gels laden with smooth muscle cells (SMCs) were molded directly within the bioreactor culture chamber. Based on a systematic characterization of the bioreactor culture mode, constructs were subjected to 10% cyclic strain at 0.5 Hz for 5 days. The effects of cyclic stimulation on matrix re-arrangement and biomechanical/viscoelastic properties were examined and compared vs. statically cultured constructs. A thorough comparison of cell response in terms of cell localization and expression of contractile phenotypic markers was carried out as well. We found that cyclic stimulation promoted cell-driven collagen matrix bi-axial compaction, enhancing the mechanical strength of strained samples with respect to static controls. Moreover, cyclic strain positively affected SMC behavior: cells maintained their contractile phenotype and spread uniformly throughout the whole wall thickness. Conversely, static culture induced a noticeable polarization of cell distribution to the outer rim of the constructs and a sharp reduction in total cell density. Overall, coupling the use of a novel dual-mode bioreactor with engineered collagen-gel-based tubular constructs demonstrated to be an interesting technology to investigate the modulation of cell and tissue behavior under controlled mechanically conditioned in vitro maturation.

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Acknowledgments

NB was awarded of a Ph.D. Scholarship from the Italian Ministry of Education, completed with a mobility scholarship from the InterPolytechnic Doctoral School. This work was partially funded by the Natural Science and Engineering Research Council of Canada, the Canadian Institute for Health Research, the Heart and Stroke Foundation of Canada, the Canadian Foundation for Innovation, and the CHU de Quebec Research Center.

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  1. μBS Lab, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133, Milan, Italy

    N. Bono, M. Soncini, M. Piola & Gianfranco Beniamino Fiore

  2. Laboratory for Biomaterials and Bioengineering (CRC-I), Department of Min-Met-Materials & CHU de Québec Research Center, Laval University, Pavillon Pouliot, Quebec City, QC, G1V 0A6, Canada

    N. Bono, S. Meghezi & D. Mantovani

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  1. N. Bono
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  2. S. Meghezi
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Bono, N., Meghezi, S., Soncini, M. et al. A Dual-Mode Bioreactor System for Tissue Engineered Vascular Models. Ann Biomed Eng 45, 1496–1510 (2017). https://doi.org/10.1007/s10439-017-1813-9

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