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.
published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal.If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User
The transition in the field of bone tissue engineering from bone regeneration to three-dimensional in vitro models has come with the challenge of recreating a dense and anisotropic bone-like extracellular matrix with cell culture. The creation of such an organized bone-like extracellular matrix has received little attention thus far. Although the mechanism by which bone extracellular matrix gains its structure is not fully understood, curvature (especially concavities), mechanical loading due to deformations or directional fluid flow, and osteocyte signaling have been identified as potential contributors. Here, guided by computational simulations, we evaluated three-dimensional cell and bone-like tissue growth and organization in a concave channel with and without directional fluid flow stimulation. Human bone-marrow derived mesenchymal stromal cells were seeded on donut-shaped silk fibroin scaffolds and stimulated to undergo osteogenic differentiation for 42 days statically or in a flow perfusion bioreactor. Constructs were investigated for cell distribution, and tissue growth and organization on day 14, 28, and 42. As a result, directional fluid flow was able to improve bone-like tissue growth but not organization. After 28 days of culture, when osteogenic differentiation was likely accomplished, cells tended to have a small preference for orientation in the tangential (i.e., circumferential) direction of the channel. Based on our results, we suggest that three-dimensional bone-like tissue anisotropy might be guided by curvature, while extracellular matrix production can be increased through the application of fluid shear stress. With this study, an initial attempt in three-dimensions was made to improve the resemblance of in vitro produced bone-like extracellular matrix to the physiological bone extracellular matrix.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.