Apparent elastic modulus of ex vivo trabecular bovine bone increases with dynamic loading

Vivanco, Juan; Garcia, Sylvana; Ploeg, Heidi‐Lynn; Alvarez, Gwen; Cullen, D. M.; Smith, Everett L.

doi:10.1177/0954411913486855

Cited by 27 publications

(34 citation statements)

References 28 publications

(38 reference statements)

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“…The application of simulated jumping strains resulted in increased bone formation parameters in some samples, and most importantly, architectural changes in the trabecular bone tissue [82]. Furthermore, application of load resulted in changes in the apparent stiffness of the bone samples [83]. Similar results were reported in a rabbit trabecular bone explant model cultured in a perfusion/loading system, where mechanical loading resulted in new bone deposition demonstrated by osteoid formation and the presence of double fluorochrome labelled surfaces [84].…”

Section: A Three-dimensional Trabecular Bone Explant Model Of Bone Adsupporting

confidence: 68%

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems

Brown¹,

Sattler²

2016

Interface Focus.

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Despite advancements in technology and science over the last century, the mechanisms underlying Wolff's law—bone structure adaptation in response to physical stimuli—remain poorly understood, limiting the ability to effectively treat and prevent skeletal diseases. A challenge to overcome in the study of the underlying mechanisms of this principle is the multiscale nature of mechanoadaptation. While there exist in silico systems that are capable of studying across these scales, experimental studies are typically limited to interpretation at a single dimension or time point. For instance, studies of single-cell responses to defined physical stimuli offer only a limited prediction of the whole bone response, while overlapping pathways or compensatory mechanisms complicate the ability to isolate critical targets in a whole animal model. Thus, there exists a need to develop experimental systems capable of bridging traditional experimental approaches and informing existing multiscale theoretical models. The purpose of this article is to review the process of mechanoadaptation and inherent challenges in studying its underlying mechanisms, discuss the limitations of traditional experimental systems in capturing the many facets of this process and highlight three multiscale experimental systems which bridge traditional approaches and cover relatively understudied time and length scales in bone adaptation.

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Section: A Three-dimensional Trabecular Bone Explant Model Of Bone Adsupporting

confidence: 68%

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems

Brown¹,

Sattler²

2016

Interface Focus.

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“…20 In vitro studies of trabecular bone explants have previously been used to examine bone formation in response to compression of the bone matrix. 14,15,17,24,29,44 Greater bone growth attributed to bone strain was found in samples exposed to the mechanical loading compared to control static samples, 14,29 reproducing the in vivo effects of mechanical strain on bone growth.…”

Section: Introductionmentioning

confidence: 79%

“…14,15,17,24,29,44 The objective was to examine whether the shear stress generated in trabecular bone marrow due to physiological compression of bone was of a sufficient magnitude to generate an anabolic response in the bone. l-CT scans of experimental bone explants were used to generate the meshes for computational analysis.…”

Section: Introductionmentioning

confidence: 99%

An Experimental and Computational Investigation of Bone Formation in Mechanically Loaded Trabecular Bone Explants

et al. 2015

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Understanding how bone marrow multipotent stromal cells (MSCs) contribute to new bone formation and remodeling in vivo is of principal importance for informing the development of effective bone tissue engineering strategies in vitro. However, the precise in situ stimuli that MSCs experience have not been fully established. The shear stress generated within the bone marrow of physiologically loaded samples has never been determined, but could be playing an important role in the generation of sufficient stimulus for MSCs to undergo osteogenic differentiation. In this study fluid structure interaction (FSI) computational models were used in conjunction with a bioreactor which physiologically compresses explanted trabecular bone samples to determine whether MSCs can be directly stimulated by mechanical cues within the bone marrow. Experimentally loaded samples were found to have greater osteogenic activity, as verified by bone histomorphometry, compared to control static samples. FSI models demonstrated a linear relationship between increasing shear stress and decreasing bone volume. The FSI models demonstrated that bone strain, not marrow shear stress, was likely the overall driving mechanical signal for new bone formation during compression. However, the shear stress generated in the models is within the range of values which has been shown previously to generate an osteogenic response in MSCs.

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“…The concentration of big ET1 used in the current experiment was approximately equivalent to the lowest published concentration of active ET1 used in cell culture experiments [29]. Cores in the LC and LE treatment groups were loaded (−2000 με, 120 cycles daily, “jump” waveform) through the bioreactors’ sapphire pistons using ZETOS Bone Loading and Bioreactor System (ZETOS) [9–13, 30–32]. Bone formation in the cores was assessed with ΔE app , static and dynamic histomorphometry, and PGE2 secretion.…”

Section: Methodsmentioning

confidence: 99%

“…He postulated the existence of a strain set point; with ambient strains below it eliciting bone resorption and ambient strains above it eliciting bone formation [7, 8]. Studies by the authors and others on ex vivo cultured trabecular bone cores exposed to mechanical bulk strains of −2,000 to −4,000 με found, in comparison to controls, increased percent change in apparent elastic modulus ( ΔE app ), histological and biological markers of bone formation, demonstrating that bone’s response to load can be recapitulated in an organ culture system [9–14]. Ex vivo testing provides a controlled environment, without systemic effects, to investigate mechanotransduction in live bone.…”

Section: Introductionmentioning

confidence: 99%

Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis

Meyer

Johnson

Cullen

et al. 2016

Bone

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Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-1 (big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2×2 factorial trial of daily mechanical loading (−2000 με, 120 cycles daily, “jump” waveform) and big ET1 (25 ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23 days. The bone cores’ response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (ΔEapp), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher’s LSD test found no significant treatment effects on ΔEapp (p=0.25 and 0.51 for load and big ET1, respectively). The ΔEapp in the “no load + big ET1” (CE, 13±12.2%, p=0.56), “load + no big ET1” (LC, 17±3.9%, p=0.14) and “load + big ET1” (LE, 19±4.2%, p=0.13) treatment groups were not statistically different than the control group (CC, 3.3%±8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (p=0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (p=0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (p=0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (p=0.037, p=0.055 respectively) and MAR (p=0.0040, p=0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (p=0.019) and LC (p=0.074) than CC. The PGE2 levels were elevated at 8 days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15, 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses.

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Apparent elastic modulus of ex vivo trabecular bovine bone increases with dynamic loading

Cited by 27 publications

References 28 publications

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems

An Experimental and Computational Investigation of Bone Formation in Mechanically Loaded Trabecular Bone Explants

Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis

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