A finite element inverse analysis to assess functional improvement during the fracture healing process

Weis, Jared A.; Miga, Michael I.; Granero‐Moltó, Froilán; Spagnoli, Anna

doi:10.1016/j.jbiomech.2009.09.051

Cited by 18 publications

(32 citation statements)

References 29 publications

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“…In previous work, the approach was reported using a linear Hookean elastic model of the callus [1]. It analyzed the 10-day and 14-day healing time point data reported here and found that the inverse-based metric was the only metric to show statistical significance.…”

Section: Introductionmentioning

confidence: 84%

“…The process is iterative until the relative error between iterations converges below a set tolerance or until no improvement in objective function is noted. With respect to reporting the values in this paper, the Lame' constants were reported but they were also converted to Young's modulus and Poisson's ratio for the purpose of comparing with the more traditional metrics and the results from [1].…”

Section: Geometric Nonlinear Approach To An Inverse Elasticity Analysismentioning

confidence: 99%

“…Using this methodology, a preliminary study (n=6) was conducted where there were no differences in treatment post tibia fracture except that half of the mice were allowed to heal 4 days longer (10 day, and 14 day healing respectively) [1]. Intuitively, mice allowed to heal longer should have a more stabilized callus (i.e.…”

Section: Experimental Murine Systemmentioning

confidence: 99%

“…Figure 2 is an example of a microCT volume of data from this preliminary fracture/callus healing study [1]. These microCT reconstructions were then used for subsequent FE analysis and volume measurements.…”

Section: Experimental Murine Systemmentioning

confidence: 99%

“…Displacement and force data were recorded until failure. Reproduced from [1], Figure 3 shows the data from all 6 subjects. While distinction among the two groups can be seen visually, there is a significant amount of spread within each group.…”

Section: Experimental Murine Systemmentioning

confidence: 99%

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Quantifying mechanical properties in a murine fracture healing system using inverse modeling: preliminary work

et al. 2010

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Understanding bone remodeling and mechanical property characteristics is important for assessing treatments to accelerate healing or in developing diagnostics to evaluate successful return to function. The murine system whereby mid-diaphaseal tibia fractures are imparted on the subject and fracture healing is assessed at different time points and under different therapeutic conditions is a particularly useful model to study. In this work, a novel inverse geometric nonlinear elasticity modeling framework is proposed that can reconstruct multiple mechanical properties from uniaxial testing data. To test this framework, the Lame' constants were reconstructed within the context of a murine cohort (n=6) where there were no differences in treatment post tibia fracture except that half of the mice were allowed to heal 4 days longer (10 day, and 14 day healing time point, respectively). The properties reconstructed were a shear modulus of G=511.2 ± 295.6 kPa, and 833.3± 352.3 kPa for the 10 day, and 14 day time points respectively. The second Lame' constant reconstructed at λ=1002.9 ±42.9 kPa, and 14893.7 ± 863.3 kPa for the 10 day, and 14 day time points respectively. An unpaired Student t-test was used to test for statistically significant differences among the groups. While the shear modulus did not meet our criteria for significance, the second Lame' constant did at a value p<0.0001. Traditional metrics that are commonly used within the bone fracture healing research community were not found to be statistically significant.

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Section: Introductionmentioning

confidence: 84%

Section: Geometric Nonlinear Approach To An Inverse Elasticity Analysismentioning

confidence: 99%

Section: Experimental Murine Systemmentioning

confidence: 99%

Section: Experimental Murine Systemmentioning

confidence: 99%

Section: Experimental Murine Systemmentioning

confidence: 99%

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Quantifying mechanical properties in a murine fracture healing system using inverse modeling: preliminary work

et al. 2010

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Replacement, refinement, and reduction: Necessity of standardization and computational models for long bone fracture repair in animals

Reifenrath

Angrisani

Lalk

et al. 2013

J Biomedical Materials Res

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In the field of fracture healing it is essential to know the impacts of new materials. Fracture healing of long bones is studied in various animal models and extrapolated for use in humans, although there are differences between the micro- and macrostructure of human versus animal bone. Unfortunately, recommended standardized models for fracture repair studies do not exist. Many different study designs with various animal models are used. Concerning the general principles of replacement, refinement and reduction in animal experiments (three "Rs"), a standardization would be desirable to facilitate better comparisons between different studies. In addition, standardized methods allow better prediction of bone healing properties and implant requirements with computational models. In this review, the principles of bone fracture healing and differences between osteotomy and artificial fracture models as well as influences of fixation devices are summarized. Fundamental considerations regarding animal model choice are discussed, as it is very important to know the limitations of the chosen model. In addition, a compendium of common animal models is assembled with special focus on rats, rabbits, and sheep as most common fracture models. Fracture healing simulation is a basic tool in reducing the number of experimental animals, so its progress is also presented here. In particular, simulation of different animal models is presented. In conclusion, a standardized fracture model is of utmost importance for the best adaption of simulation to experimental setups and comparison between different studies. One of the basic goals should be to reach a consensus for standardized fracture models.

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BMP2 Regulation of CXCL12 Cellular, Temporal, and Spatial Expression Is Essential During Fracture Repair

Myers

Longobardi

Willcockson

et al. 2015

Journal of Bone and Mineral Research

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The cellular and humoral responses that orchestrate fracture healing are still elusive. Here we report that bone morphogenic protein 2 (BMP2)-dependent fracture healing occurs through a tight control of chemokine C-X-C motif-ligand-12 (CXCL12) cellular, spatial, and temporal expression. We found that the fracture repair process elicited an early site-specific response of CXCL12+-BMP2+ endosteal cells and osteocytes that was not present in unfractured bones and gradually decreased as healing progressed. Absence of a full complement of BMP2 in mesenchyme osteoprogenitors (BMP2cKO/+) prevented healing and led to a dysregulated temporal and cellular upregulation of CXCL12 expression associated with a deranged angiogenic response. Healing was rescued when BMP2cKO/+ mice were systemically treated with AMD3100, an antagonist of CXCR4 and agonist for CXCR7 both receptors for CXCL12. We further found that mesenchymal stromal cells (MSCs), capable of delivering BMP2 at the endosteal site, restored fracture healing when transplanted into BMP2cKO/+ mice by rectifying the CXCL12 expression pattern. Our in vitro studies showed that in isolated endosteal cells, BMP2, while inducing osteoblastic differentiation, stimulated expression of pericyte markers that was coupled with a decrease in CXCL12. Furthermore, in isolated BMP2cKO/cKO endosteal cells, high expression levels of CXCL12 inhibited osteoblastic differentiation that was restored by AMD3100 treatment or coculture with BMP2-expressing MSCs that led to an upregulation of pericyte markers while decreasing platelet endothelial cell adhesion molecule (PECAM). Taken together, our studies show that following fracture, a CXCL12+-BMP2+ perivascular cell population is recruited along the endosteum, then a timely increase of BMP2 leads to downregulation of CXCL12 that is essential to determine the fate of the CXCL12+-BMP2+ to osteogenesis while departing their supportive role to angiogenesis. Our findings have far-reaching implications for understanding mechanisms regulating the selective recruitment of distinct cells into the repairing niches and the development of novel pharmacological (by targeting BMP2/CXCL12) and cellular (MSCs, endosteal cells) interventions to promote fracture healing.

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A finite element inverse analysis to assess functional improvement during the fracture healing process

Cited by 18 publications

References 29 publications

Quantifying mechanical properties in a murine fracture healing system using inverse modeling: preliminary work

Quantifying mechanical properties in a murine fracture healing system using inverse modeling: preliminary work

Replacement, refinement, and reduction: Necessity of standardization and computational models for long bone fracture repair in animals

BMP2 Regulation of CXCL12 Cellular, Temporal, and Spatial Expression Is Essential During Fracture Repair

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