An In Vivo Ovine Model of Bone Tissue Alterations in Simulated Microgravity Conditions

McGilvray

Easley

et al. 2017

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The use of shock wave therapy (SWT) and low‐intensity pulsed ultrasound (LIPUS) as countermeasures to the inhibited fracture healing experienced during mechanical unloading was investigated by administering treatment to the fracture sites of mature, female, Rambouillet Columbian ewes exposed to partial mechanical unloading or full gravitational loading. The amount of fracture healing experienced by the treatment groups was compared to controls in which identical surgical and testing protocols were administered except for SWT or LIPUS treatment. All groups were euthanized after a 28‐day healing period. In vivo mechanical measurements demonstrated no significant alteration in fixation plate strains between treatments within either partial unloading group. Similarly, DXA BMD and 4‐point bending stiffness were not significantly altered following either treatment. μCT analyses demonstrated lower callus bone volume for treated animals (SWT and LIPUS, p < 0.01) in the full gravity group but not between reduced loading groups. Callus osteoblast numbers as well as mineralized surface and bone formation rate were significantly elevated to the level of the full gravity groups in the reduced loading groups following both SWT and LIPUS. Although no increase in 4‐week mechanical strength was observed, it is possible that an increase in the overall rate of fracture healing (i.e., callus strength) may be experienced at longer time points under partial loading conditions given the increase in osteoblast numbers and bone formation parameters following SWT and LIPUS. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:921–929, 2018.

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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An investigation of shock wave therapy and low‐intensity pulsed ultrasound on fracture healing under reduced loading conditions in an ovine model

McGilvray

Easley

et al. 2017

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“…The effects of simulated hypogravity on bone remodeling and fracture healing were previously investigated in two large animal (sheep) studies . Animal use approval was granted by the Colorado State University Animal Care and Use Committee (Approval #11‐2938A).…”

Section: Methodsmentioning

confidence: 99%

“…Model predictions at the proximal metaphysis, distal metaphysis, and the mid‐diaphysis were compared to their corresponding in vivo metatarsal bone strains at pre‐determined GRFs from the previously described animal study (for single‐limb vertical GRFs up to 300 N; n = 5 animals per group) . Previously established correlations between bone and orthopaedic plate strains were utilized to calculate the corresponding strains . Linear regression analyses were performed ( α = 0.05) to demonstrate the level of agreement between model predictions and experimental strain data for 100, 200, and 300 N standing GRFs (SigmaPlot, Systat Software, Inc., San Jose, CA).…”

Section: Methodsmentioning

confidence: 99%

Computational characterization of fracture healing under reduced gravity loading conditions

Lerner

Browning

et al. 2016

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ABSTRACT:The literature is deficient with regard to how the localized mechanical environment of skeletal tissue is altered during reduced gravitational loading and how these alterations affect fracture healing. Thus, a finite element model of the ovine hindlimb was created to characterize the local mechanical environment responsible for the inhibited fracture healing observed under experimental simulated hypogravity conditions. Following convergence and verification studies, hydrostatic pressure and strain within a diaphyseal fracture of the metatarsus were evaluated for models under both 1 and 0.25 g loading environments and compared to results of a related in vivo study. Results of the study suggest that reductions in hydrostatic pressure and strain of the healing fracture for animals exposed to reduced gravitational loading conditions contributed to an inhibited healing process, with animals exposed to the simulated hypogravity environment subsequently initiating an intramembranous bone formation process rather than the typical endochondral ossification healing process experienced by animals healing in a 1 g gravitational environment. The literature is deficient with regard to the specific alterations in the localized mechanical environment of skeletal tissue during the reduced gravitational loading characteristic of spaceflight and how these alterations affect fracture healing in Haversian systems. Additionally, investigations that have attempted to link the direct role of these reduced gravitational forces to fracture healing have been limited primarily to rodent studies. [1][2][3][4] The in vivo studies that have been reported have consistently demonstrated that weight-bearing maintains skeletal integrity, and ultimately, accelerates the healing of long bone fractures by promoting rapid callus formation.5 However, the lack of mechanical loading experienced during weightlessness leads to the inhibition of fracture healing. [1][2][3][4] More specifically, these studies have demonstrated decreased chondrogenesis, mechanical strength, callus size, osteoblast activity, and bone formation rates in animals that healed in reduced loading environments as compared to those that healed in a full Earth gravity loading condition.1-4 Despite the limited number of studies directly investigating fracture healing in reduced gravitational loading environments, numerous ground-based studies have examined the effect of fixation rigidity on subsequent fracture healing on Earth. A large number of these studies relied on external fixation devices that allowed predefined amounts of axial movement in order to investigate the magnitude of interfragmentary motion necessary to alter fracture healing in both animal models and human patient cohorts. [6][7][8][9][10][11][12] It has also been demonstrated that rigid fixation has a deleterious impact on the fracture healing cascade while improved fracture healing occurred when axial micromotion is delivered to the fracture site. [13][14][15] While these studies provide valuable insight ab...

Modulating tibiofemoral contact force in the sheep hind limb via treadmill walking: Predictions from an opensim musculoskeletal model

Lerner

Ipson

et al. 2015

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Sheep are a predominant animal model used to study a variety of orthopedic conditions. Understanding and controlling the in-vivo loading environment in the sheep hind limb is often necessary for investigations relating to bone and joint mechanics. The purpose of this study was to develop a musculoskeletal model of an adult sheep hind limb and investigate the effects of treadmill walking speed on muscle and joint contact forces. We constructed the skeletal geometry of the model from computed topography images. Dual-energy x-ray absorptiometry was utilized to establish the inertial properties of each model segment. Detailed dissection and tendon excursion experiments established the requisite muscle lines of actions. We used OpenSim and experimentally-collected marker trajectories and ground reaction forces to quantify muscle and joint contact forces during treadmill walking at 0. 5 Since mechanical stimuli affect the biosynthesis, remodeling, and degradation of biological tissues, proper investigation of many such orthopedic conditions requires knowledge, and standardization of the loading environment in the sheep hind limb.6-9 The combination of treadmill locomotion and musculoskeletal modeling may allow researchers to modulate and quantify muscle and joint contact forces in-vivoIn humans, peak compressive and anterior-posterior tibiofemoral contact forces are proportional to walking speed. 10 This suggests that treadmill walking at set speeds may be a way to manipulate in-vivo loading in the sheep hind limb. However, it is unknown how walking speed alters sheep hind limb loading. Joint contact forces have only been reported for self-selected over-ground walking speeds in sheep and are therefore highly variable with standard deviations of AE50% of body weight (BW) at peak loading.11,12 Furthermore, sheep may be noncompliant and erratic during treadmill walking, and since quadrupeds have the ability to unweight and vary loading within individual limbs to a greater extent than bipeds, 13 the variability of loading during treadmill locomotion at set speeds in sheep is unknown.Musculoskeletal models and analysis software offer a method to non-invasively estimate the mechanical loads (i.e., muscle and joint contact forces) in weightbearing limbs during locomotor activites.14-16 However, while there are many open-source musculoskeletal models available to estimate muscle and joint contact forces in humans, 17 we are not aware of a freelyavailable model of the sheep hind limb.This study had two aims. The first aim was to develop a freely-available musculoskeletal model of the sheep hind limb for use in OpenSim. 16 The second aim was to determine how treadmill walking speed alters estimates of in-vivo joint loading in the sheep hind limb. This was accomplished by quantifying tibiofemoral contact forces from the musculoskeletal model while the animal walked on a treadmill at 0.25m• s À1 and 0.75m• s À1. The tibiofemoral joint was identified as the focus of this study due to the ease of translation between sheep...