Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in Mice
Bone healing and remodeling are mechanically driven processes. While the generalized response to mechanical stimulation in bone is well-understood, much less is known about the mechanobiology-regulating tissue-scale bone formation and resorption during the reparative and remodeling phases of fractur...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.856204/full |
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| author | Graeme R. Paul Paul Vallaster Michelle Rüegg Ariane C. Scheuren Duncan C. Tourolle Gisela A. Kuhn Esther Wehrle Ralph Müller |
| author_facet | Graeme R. Paul Paul Vallaster Michelle Rüegg Ariane C. Scheuren Duncan C. Tourolle Gisela A. Kuhn Esther Wehrle Ralph Müller |
| author_sort | Graeme R. Paul |
| collection | DOAJ |
| description | Bone healing and remodeling are mechanically driven processes. While the generalized response to mechanical stimulation in bone is well-understood, much less is known about the mechanobiology-regulating tissue-scale bone formation and resorption during the reparative and remodeling phases of fracture healing. In this study, we combined computational approaches in the form of finite element analysis and experimental approaches by using a loaded femoral defect model in mice to investigate the role of mechanical stimulation in the microenvironment of bone. Specifically, we used longitudinal micro-computed tomography to observe temporal changes in bone at different densities and micro-finite element analysis to map the mechanics of the microenvironment to tissue-scale formation, quiescence (no change in bone presence between time points), and resorption dynamics in the late reparative and remodeling phases (post bridging). Increasing levels of effective strain led to increasing conditional probability of bone formation, while decreasing levels of effective strain led to increasing probability of bone resorption. In addition, the analysis of mineralization dynamics showed both a temporal and effective strain level-dependent behavior. A logarithmic-like response was displayed, where the conditional probability of bone formation or resorption increased rapidly and plateaued or fell rapidly and plateaued as mechanical strain increased. |
| first_indexed | 2024-04-14T04:39:26Z |
| format | Article |
| id | doaj.art-dfab17a43c7b4a1aade902e129c0d2ff |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-14T04:39:26Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-dfab17a43c7b4a1aade902e129c0d2ff2022-12-22T02:11:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-05-011010.3389/fcell.2022.856204856204Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in MiceGraeme R. PaulPaul VallasterMichelle RüeggAriane C. ScheurenDuncan C. TourolleGisela A. KuhnEsther WehrleRalph MüllerBone healing and remodeling are mechanically driven processes. While the generalized response to mechanical stimulation in bone is well-understood, much less is known about the mechanobiology-regulating tissue-scale bone formation and resorption during the reparative and remodeling phases of fracture healing. In this study, we combined computational approaches in the form of finite element analysis and experimental approaches by using a loaded femoral defect model in mice to investigate the role of mechanical stimulation in the microenvironment of bone. Specifically, we used longitudinal micro-computed tomography to observe temporal changes in bone at different densities and micro-finite element analysis to map the mechanics of the microenvironment to tissue-scale formation, quiescence (no change in bone presence between time points), and resorption dynamics in the late reparative and remodeling phases (post bridging). Increasing levels of effective strain led to increasing conditional probability of bone formation, while decreasing levels of effective strain led to increasing probability of bone resorption. In addition, the analysis of mineralization dynamics showed both a temporal and effective strain level-dependent behavior. A logarithmic-like response was displayed, where the conditional probability of bone formation or resorption increased rapidly and plateaued or fell rapidly and plateaued as mechanical strain increased.https://www.frontiersin.org/articles/10.3389/fcell.2022.856204/fullbonemechanobiologyfracture healingadaptive loadingreal-time finite element analysismicroenvironment |
| spellingShingle | Graeme R. Paul Paul Vallaster Michelle Rüegg Ariane C. Scheuren Duncan C. Tourolle Gisela A. Kuhn Esther Wehrle Ralph Müller Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in Mice Frontiers in Cell and Developmental Biology bone mechanobiology fracture healing adaptive loading real-time finite element analysis microenvironment |
| title | Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in Mice |
| title_full | Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in Mice |
| title_fullStr | Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in Mice |
| title_full_unstemmed | Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in Mice |
| title_short | Tissue-Level Regeneration and Remodeling Dynamics are Driven by Mechanical Stimuli in the Microenvironment in a Post-Bridging Loaded Femur Defect Healing Model in Mice |
| title_sort | tissue level regeneration and remodeling dynamics are driven by mechanical stimuli in the microenvironment in a post bridging loaded femur defect healing model in mice |
| topic | bone mechanobiology fracture healing adaptive loading real-time finite element analysis microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.856204/full |
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