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Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures

Marina Rubert, Jolanda Rita Vetsch, Iina Lehtoviita, Marianne Sommer, Feihu Zhao Orcid Logo, André R. Studart, Ralph Müller, Sandra Hofmann

Tissue Engineering Part A, Volume: 27, Issue: 17-18, Pages: 1192 - 1204

Swansea University Author: Feihu Zhao Orcid Logo

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DOI (Published version): 10.1089/ten.tea.2020.0121

Abstract

Cells sense and respond to scaffold pore geometry and mechanical stimuli. Many fabrication methods used in bone tissue engineering render structures with poorly controlled pore geometries. Given that cell–scaffold interactions are complex, drawing a conclusion on how cells sense and respond to uncon...

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Published in: Tissue Engineering Part A
ISSN: 1937-3341 1937-335X
Published: Mary Ann Liebert Inc 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa58125
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first_indexed 2021-09-28T10:23:41Z
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spelling 2022-10-31T19:04:59.4658847 v2 58125 2021-09-28 Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures 1c6e79b6edd08c88a8d17a241cd78630 0000-0003-0515-6808 Feihu Zhao Feihu Zhao true false 2021-09-28 MEDE Cells sense and respond to scaffold pore geometry and mechanical stimuli. Many fabrication methods used in bone tissue engineering render structures with poorly controlled pore geometries. Given that cell–scaffold interactions are complex, drawing a conclusion on how cells sense and respond to uncontrolled scaffold features under mechanical loading is difficult. In this study, monodisperse templated scaffolds (MTSC) were fabricated and used as well-defined porous scaffolds to study the effect of dynamic culture conditions on bone-like tissue formation. Human bone marrow-derived stromal cells were cultured on MTSC or conventional salt-leached scaffolds (SLSC) for up to 7 weeks, either under static or dynamic conditions (wall shear stress [WSS] using spinner flask bioreactors). The influence of controlled spherical pore geometry of MTSC subjected to static or dynamic conditions on osteoblast cell differentiation, bone-like tissue formation, structure, and distribution was investigated. WSS generated within the two idealized geometrical scaffold features was assessed. Distinct response to fluid flow in osteoblast cell differentiation were shown to be dependent on scaffold pore geometry. As revealed by collagen staining and microcomputed tomography images, dynamic conditions promoted a more regular extracellular matrix (ECM) formation and mineral distribution in both scaffold types compared with static conditions. The results showed that regulation of bone-related genes and the amount and the structure of mineralized ECM were dependent on scaffold pore geometry and the mechanical cues provided by the two different culture conditions. Under dynamic conditions, SLSC favored osteoblast cell differentiation and ECM formation, whereas MTSC enhanced ECM mineralization. The spherical pore shape in MTSC supported a more trabecular bone-like structure under dynamic conditions compared with MTSC statically cultured or to SLSC under either static or dynamic conditions. These results suggest that cell activity and bone-like tissue formation is driven not only by the pore geometry but also by the mechanical environment. This should be taken into account in the future design of complex scaffolds, which should favor cell differentiation while guiding the formation, structure, and distribution of the engineered bone tissue. This could help to mimic the anatomical complexity of the bone tissue structure and to adapt to each bone defect needs. Journal Article Tissue Engineering Part A 27 17-18 1192 1204 Mary Ann Liebert Inc 1937-3341 1937-335X 1 9 2021 2021-09-01 10.1089/ten.tea.2020.0121 COLLEGE NANME Biomedical Engineering COLLEGE CODE MEDE Swansea University 2022-10-31T19:04:59.4658847 2021-09-28T10:43:38.0211787 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering Marina Rubert 1 Jolanda Rita Vetsch 2 Iina Lehtoviita 3 Marianne Sommer 4 Feihu Zhao 0000-0003-0515-6808 5 André R. Studart 6 Ralph Müller 7 Sandra Hofmann 8
title Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures
spellingShingle Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures
Feihu Zhao
title_short Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures
title_full Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures
title_fullStr Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures
title_full_unstemmed Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures
title_sort Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures
author_id_str_mv 1c6e79b6edd08c88a8d17a241cd78630
author_id_fullname_str_mv 1c6e79b6edd08c88a8d17a241cd78630_***_Feihu Zhao
author Feihu Zhao
author2 Marina Rubert
Jolanda Rita Vetsch
Iina Lehtoviita
Marianne Sommer
Feihu Zhao
André R. Studart
Ralph Müller
Sandra Hofmann
format Journal article
container_title Tissue Engineering Part A
container_volume 27
container_issue 17-18
container_start_page 1192
publishDate 2021
institution Swansea University
issn 1937-3341
1937-335X
doi_str_mv 10.1089/ten.tea.2020.0121
publisher Mary Ann Liebert Inc
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Biomedical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Biomedical Engineering
document_store_str 0
active_str 0
description Cells sense and respond to scaffold pore geometry and mechanical stimuli. Many fabrication methods used in bone tissue engineering render structures with poorly controlled pore geometries. Given that cell–scaffold interactions are complex, drawing a conclusion on how cells sense and respond to uncontrolled scaffold features under mechanical loading is difficult. In this study, monodisperse templated scaffolds (MTSC) were fabricated and used as well-defined porous scaffolds to study the effect of dynamic culture conditions on bone-like tissue formation. Human bone marrow-derived stromal cells were cultured on MTSC or conventional salt-leached scaffolds (SLSC) for up to 7 weeks, either under static or dynamic conditions (wall shear stress [WSS] using spinner flask bioreactors). The influence of controlled spherical pore geometry of MTSC subjected to static or dynamic conditions on osteoblast cell differentiation, bone-like tissue formation, structure, and distribution was investigated. WSS generated within the two idealized geometrical scaffold features was assessed. Distinct response to fluid flow in osteoblast cell differentiation were shown to be dependent on scaffold pore geometry. As revealed by collagen staining and microcomputed tomography images, dynamic conditions promoted a more regular extracellular matrix (ECM) formation and mineral distribution in both scaffold types compared with static conditions. The results showed that regulation of bone-related genes and the amount and the structure of mineralized ECM were dependent on scaffold pore geometry and the mechanical cues provided by the two different culture conditions. Under dynamic conditions, SLSC favored osteoblast cell differentiation and ECM formation, whereas MTSC enhanced ECM mineralization. The spherical pore shape in MTSC supported a more trabecular bone-like structure under dynamic conditions compared with MTSC statically cultured or to SLSC under either static or dynamic conditions. These results suggest that cell activity and bone-like tissue formation is driven not only by the pore geometry but also by the mechanical environment. This should be taken into account in the future design of complex scaffolds, which should favor cell differentiation while guiding the formation, structure, and distribution of the engineered bone tissue. This could help to mimic the anatomical complexity of the bone tissue structure and to adapt to each bone defect needs.
published_date 2021-09-01T04:14:24Z
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