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Characterization of three-dimensional bone-like tissue growth and organization under influence of directional fluid flow
Authors:Bregje W M de Wildt  Feihu Zhao  Iris Lauwers  Bert van Rietbergen  Keita Ito  Sandra Hofmann
Institution:1. Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands;2. Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands

Biomedical Engineering, Zienkiewicz Centre for Computational Engineering, Faculty of Science and Engineering, Swansea University, Swansea, UK;3. Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands

Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands

Abstract:The transition in the field of bone tissue engineering from bone regeneration to in vitro models has come with the challenge of recreating a dense and anisotropic bone-like extracellular matrix (ECM). Although the mechanism by which bone ECM gains its structure is not fully understood, mechanical loading and curvature have been identified as potential contributors. Here, guided by computational simulations, we evaluated cell and bone-like tissue growth and organization in a concave channel with and without directional fluid flow stimulation. Human mesenchymal stromal cells were seeded on donut-shaped silk fibroin scaffolds and osteogenically stimulated for 42 days statically or in a flow perfusion bioreactor. After 14, 28, and 42 days, constructs were investigated for cell and tissue growth and organization. As a result, directional fluid flow was able to improve organic tissue growth but not organization. Cells tended to orient in the tangential direction of the channel, possibly attributed to its curvature. Based on our results, we suggest that organic ECM production but not anisotropy can be stimulated through the application of fluid flow. With this study, an initial attempt in three-dimensions was made to improve the resemblance of in vitro produced bone-like ECM to the physiological bone ECM.
Keywords:bone tissue engineering  cell and tissue organization  computational fluid dynamics model  extracellular matrix  in vitro model
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