Mechanoregulation analysis of bone formation in tissue engineered constructs requires a volumetric method using time-lapsed micro-computed tomography.

Autor: Griesbach JK; Institute for Biomechanics, ETH Zürich, Gloriastrasse 37/39, 8092 Zürich, Switzerland., Schulte FA; Institute for Biomechanics, ETH Zürich, Gloriastrasse 37/39, 8092 Zürich, Switzerland., Schädli GN; Institute for Biomechanics, ETH Zürich, Gloriastrasse 37/39, 8092 Zürich, Switzerland., Rubert M; Institute for Biomechanics, ETH Zürich, Gloriastrasse 37/39, 8092 Zürich, Switzerland., Müller R; Institute for Biomechanics, ETH Zürich, Gloriastrasse 37/39, 8092 Zürich, Switzerland. Electronic address: ram@ethz.ch.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 Apr 15; Vol. 179, pp. 149-163. Date of Electronic Publication: 2024 Mar 16.
DOI: 10.1016/j.actbio.2024.03.008
Abstrakt: Bone can adapt its microstructure to mechanical loads through mechanoregulation of the (re)modeling process. This process has been investigated in vivo using time-lapsed micro-computed tomography (micro-CT) and micro-finite element (FE) analysis using surface-based methods, which are highly influenced by surface curvature. Consequently, when trying to investigate mechanoregulation in tissue engineered bone constructs, their concave surfaces make the detection of mechanoregulation impossible when using surface-based methods. In this study, we aimed at developing and applying a volumetric method to non-invasively quantify mechanoregulation of bone formation in tissue engineered bone constructs using micro-CT images and FE analysis. We first investigated hydroxyapatite scaffolds seeded with human mesenchymal stem cells that were incubated over 8 weeks with one mechanically loaded and one control group. Higher mechanoregulation of bone formation was measured in loaded samples with an area under the curve for the receiver operating curve (AUC formation ) of 0.633-0.637 compared to non-loaded controls (AUC formation : 0.592-0.604) during culture in osteogenic medium (p < 0.05). Furthermore, we applied the method to an in vivo mouse study investigating the effect of loading frequencies on bone adaptation. The volumetric method detected differences in mechanoregulation of bone formation between loading conditions (p < 0.05). Mechanoregulation in bone formation was more pronounced (AUC formation : 0.609-0.642) compared to the surface-based method (AUC formation : 0.565-0.569, p < 0.05). Our results show that mechanoregulation of formation in bone tissue engineered constructs takes place and its extent can be quantified with a volumetric mechanoregulation method using time-lapsed micro-CT and FE analysis. STATEMENT OF SIGNIFICANCE: Many efforts have been directed towards optimizing bone scaffolds for tissue growth. However, the impact of the scaffolds mechanical environment on bone growth is still poorly understood, requiring accurate assessment of its mechanoregulation. Existing surface-based methods were unable to detect mechanoregulation in tissue engineered constructs, due to predominantly concave surfaces in scaffolds. We present a volumetric approach to enable the precise and non-invasive quantification and analysis of mechanoregulation in bone tissue engineered constructs by leveraging time-lapsed micro-CT imaging, image registration, and finite element analysis. The implications of this research extend to diverse experimental setups, encompassing culture conditions, and material optimization, and investigations into bone diseases, enabling a significant stride towards comprehensive advancements in bone tissue engineering and regenerative medicine.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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