Simulated Physiological Loading Research Articles

Patient-specific finite element analysis of four different fixation methods for transversely unstable radial head fractures

Plate fixation is a common treatment option for radial head fractures (RHFs). Due to the benefits of less invasiveness and fewer complications of internal fixation, the application of small-diameter headless compression screws (HCSs) to treat RHFs has become a new trend. This study aimed to compare the mechanical stability of four distinct internal fixation protocols for transversely unstable RHFs via finite element analysis. Using computed tomography data from 10 patients, we developed 40 patient-specific FE models of transversely unstable RHFs fixed by parallel, crossed, and tripod HCSs and mini-T plate (MTP). Under simulated physiological loading of the elbow joint, the construct stiffness, displacement, and von Mises stresses were evaluated and verified by a biomechanical experiment. Under shear loading, the MTP group exhibited lower construct stiffness, larger displacement, and higher Von Mises stress than the HCSs group. The stiffness of tripod HCSs was greater than parallel and crossed screw fixation techniques. There was a strong relationship between apparent bone density and construct stiffness (R = 0.98 to 0.99). In the treatment of transversely unstable RHFs, HCSs have superior biomechanical stability than MTP. The tripod technique was also more stable than parallel and crossed fixation.

Experimental study on the biomechanical stability of complex acetabular fractures in the quadrilateral area: application of a dynamic anterior titanium-plate screw system

Background and objectiveComplex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens.Materials and methodsEight formal in-preserved cadaveric pelvises aged 30–50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations.ResultsAs the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p < 0.05). In the sitting position, the horizontal and longitudinal displacements of the quadrilateral areas were within 0.5 mm in group A and group B, and there was no significant difference between group A and group B (p > 0.05).ConclusionFor complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.

Mechanical evaluation of a threaded interference interlocking mechanism for angle-stable intramedullary nailing.

To assess the fatigue and load-to-failure mechanical characteristics of an intramedullary nail with a threaded interference design (TID) in comparison to a commercially available veterinary angle-stable nail with a Morse taper bolt design (I-Loc) of an equivalent size. 10 single interlocking screw/bolt constructs of TID and I-Loc implants were assembled using steel pipe segments and placed through 50,000 cycles of simulated, physiologic axial or torsional loading. Entry torque, postfatigue extraction torque, and 10th, 25,000th, and 50,000th cycle torsional toggle were assessed. Each construct was then loaded to failure in the same respective direction as fatigue testing. Four complete constructs of each design were then assessed using a synthetic bone analog with a 50-mm central defect via nondestructive torsional and axial loading followed by axial load to failure. All constructs were angle stable at all time points and withstood fatigue loading. Median insertional torque, extraction torque-to-insertion torque ratio, and torsional yield load were 33%, 33%, and 72.5% lower, respectively, for the TID interlocking screws. No differences in torsional peak load, torsional stiffness, axial yield load, axial stiffness, or axial peak load were identified. No differences in complete construct angle stability, torsional stiffness, axial peak load, axial stiffness, or axial yield load were identified. The TID had an inferior torsional yield load when compared to I-Loc implants but generated angle stability and sustained simulated physiologic fatigue loading. The TID may be a suitable mechanism for generating angle stability in interlocking nails.

Simulation of the Mechanical Behavior of the Degradation L4-L5 Lumbar Spine

Degenerative changes in the lumbar spine significantly reduce the quality of life of people. To fully understand the biomechanics of the affected spine, it is crucial to consider the biomechanical alterations caused by degeneration of the intervertebral disc (IVD). Therefore this study is aimed at the development of a discrete element model of the mechanical behavior of the L4-L5 spinal motion segment, which covers all the degeneration grades from healthy IVD to its severe degeneration, and numerical study of the influence of the IVD degeneration on stress state and biomechanics of the spine. To analyze the effects of IVD degeneration on spine biomechanics we simulated physiological loading conditions using compressive forces. The results of modeling showed that at the initial stages of degenerative changes, an increase in the amplitude and area of maximum compressive stresses in the disc is observed. At the late stages of disc degradation, a decrease in the value of intradiscal pressure and a shift in the maximum compressive stresses in the dorsal direction are observed. Such an influence of the degradation of the geometric and mechanical parameters of the tissues of the disc leads to the effect of bulging, which in turn will lead to the formation of an intervertebral hernia.

Impact of bone health on the mechanics of plate fixation for Vancouver B1 periprosthetic femoral fractures

BackgroundCondyle-spanning plate-screw constructs have shown potential to lower the risks of femoral refractures after the healing of a primary Vancouver type B1 periprosthetic femoral fracture. Limited information exists to show how osteoporosis (a risk factor for periprosthetic femoral fractures) may affect the plate fixation during activities of daily living. MethodsUsing total hip arthroplasty and plate-implanted finite element models of three osteoporotic femurs, this study simulated physiological loads of three activities of daily living, as well as osteoporosis associated muscle weakening, and compared the calculated stress/strain, load transfer and local stiffness with experimentally validated models of three healthy femurs. Two plating systems and two construct lengths (a diaphyseal construct and a condyle-spanning construct) were modeled. FindingsOsteoporotic femurs showed higher bone strain (21.9%) and higher peak plate stress (144.3%) as compared with healthy femurs. Compared with shorter diaphyseal constructs, condyle-spanning constructs of two plating systems reduced bone strains in both healthy and osteoporotic femurs (both applying ‘the normal’ and ‘the weakened muscle forces’) around the most distal diaphyseal screw and in the distal metaphysis, both locations where secondary fractures are typically reported. The lowered resultant compressive force and the increased local compressive stiffness in the distal diaphysis and metaphysis may be associated with strain reductions via condyle-spanning constructs. InterpretationStrain reductions in condyle-spanning constructs agreed with the clinically reported lowered risks of femoral refractures in the distal diaphysis and metaphysis. Multiple condylar screws may mitigate the concentrated strains in the lateral condyle, especially in osteoporotic femurs.

Development of a Computational Model of the Mechanical Behavior of the L4-L5 Lumbar Spine: Application to Disc Degeneration.

Degenerative changes in the lumbar spine significantly reduce the quality of life of people. In order to fully understand the biomechanics of the affected spine, it is crucial to consider the biomechanical alterations caused by degeneration of the intervertebral disc (IVD). Therefore, this study is aimed at the development of a discrete element model of the mechanical behavior of the L4–L5 spinal motion segment, which covers all the degeneration grades from healthy IVD to its severe degeneration, and numerical study of the influence of the IVD degeneration on stress state and biomechanics of the spine. In order to analyze the effects of IVD degeneration on spine biomechanics, we simulated physiological loading conditions using compressive forces. The results of modeling showed that at the initial stages of degenerative changes, an increase in the amplitude and area of maximum compressive stresses in the disc is observed. At the late stages of disc degradation, a decrease in the value of intradiscal pressure and a shift in the maximum compressive stresses in the dorsal direction is observed. Such an influence of the degradation of the geometric and mechanical parameters of the tissues of the disc leads to the effect of bulging, which in turn leads to the formation of an intervertebral hernia.

Load Sharing in the Femur Using Strut Allografts: A Biomechanical Study.

BackgroundFemoral strut allografts are used in revision hip arthroplasty for management of bone loss associated with implant failure or periprosthetic fractures. They have also been used to treat unremitting thigh pain in well-fixed cementless femoral stems, to address the differential in structural stiffness between the stem and femoral shaft. Our study used an in vitro biomechanical model to measure the effect of placement of allografts on femoral strains, to determine their load-sharing capacity.Material and methodsThree rosette strain gauges were applied to the femoral surface of each of 6 cadaveric femurs, at the stem tip level on anterior, medial, and lateral cortices. After stem implantation, cortical strut allografts were applied to the lateral femoral shaft and secured with 4 Dall-Miles cables. A fourth gauge was placed on the midpoint of the allograft. Strains were recorded in the intact femur, then the implanted femur with and without the allograft under simulated physiologic loading in a load frame.ResultsReduction in distal femoral principal strains, between 12% and 59%, was seen in all cortices following placement of the allograft. Under axial loading, 30% of the strain in the lateral cortex was borne by the allograft. Greater reductions in strain, by as much as 59%, occurred under axial load and torque.ConclusionThe results of this biomechanical model indicate that by placement of an allograft, cortical strains can be reduced to levels approaching those in an intact femur, supporting this technique for treatment of unremitting thigh pain in well-fixed prostheses.

The effects of titanium mesh cage size on the biomechanical responses of cervical spine after anterior cervical corpectomy and fusion: A finite element study

BackgroundDue to the lack of sufficient studies focusing on titanium mesh cage size, there exists a puzzle among surgeons about how to determine the optimal size of cage to provide surgical segments an adequate distraction. MethodsThe biomechanical responses of cervical spine after the implantation of cages with different heights and trimmed angles were analyzed using the finite element method. Twenty Anterior Cervical Corpectomy and Fusion models, of which the surgical segment was C5, were developed corresponding to the combinations of 4-different-heights and 5-different-trimmed angle cages. Biomechanical parameters were calculated under simulated physiological load of cervical spine. A rating scale was designed to assess the biomechanical performances of titanium mesh cages with different heights and trimmed angles comprehensively, assisting to select the most appropriate combination of cage height and trimmed angle. FindingsIt was indicated that in the single-level Anterior Cervical Corpectomy and Fusion at C5 segment, a cage with a height fitting with the space between C4 and C6 as well as a trimmed angle 2° lower than the sagittal angle of C4 inferior endplate would provide adequate biomechanical environment for cervical spine to resist cage subsidence and reduce the impact to adjacent segments. InterpretationThe biomechanical responses of cervical spine are affected significantly by the height and trimmed angles of titanium mesh cage. The results of this study would provide quantitative guidance for surgeons to determine the optimal height and trimmed angle of titanium mesh cage for a specific patient in order to achieve favorable clinical outcomes.

Bone Mineralization and Spinal Fusion Evaluation of a Truss-based Interbody Fusion Device: Ovine Finite Element Analysis with Confirmatory In Vivo Outcomes.

Finite element analysis (FEA) and in vivo ovine spinal interbody fusion study. To determine comparative load-induced strain amplitudes, bone mineralization and fusion outcomes associated with different diameter struts in a truss-based interbody fusion device. Additive manufacturing technology has been employed to develop implants that actively participate in the fusion process. The truss device enables the optimal transfer of compressive and tensile stresses via the struts. Mechanobiologic principles postulate that strut diameter can be regulated to allow different magnitudes of strain distribution within the struts which may affect fusion rates. Modeling of strain distributions as a function of strut diameter (0.75, 1.0, 1.25, and 1.5 mm) employed FEA that simulated physiologic loading conditions. A confirmatory in vivo ovine lumbar spinal interbody fusion study compared fusion scores and bone histomorphometric variables for cages with 0.75 and 1.5 mm strut diameters. Outcomes were compared at 3-, 6-, and 12-month follow-up intervals. FEA showed an inverse association between strut diameter and peak strain amplitude. Cages with 1.0, 1.25, and 1.5 mm struts had peak strain values that were 36%, 60%, and 73% lower than the 0.75 mm strut strain value. In vivo results showed the mean fusion score for the 0.75 mm diameter strut cage was significantly greater by 3-months versus the 1.5 mm strut cage, and remained significantly higher at each subsequent interval (P < 0.001 for all comparisons). Fusion rates were 95%, 100%, and 100% (0.75 mm) and 72.7%, 86.4%, and 95.8% (1.5 mm) at 3, 6, and 12 months. Thinner struts had greater mineralized bone tissue and less fibrous/chondral tissue than the thicker struts at each follow-up. Validating FEA estimates, cages with smaller diameter struts exhibited more rapid fusion consolidation and more aggressive osseointegration compared with cages with larger diameters struts.Level of Evidence: 4.

Influence of structural and material property uncertainties on biomechanics of intervertebral discs - Implications for disc tissue engineering

This study investigated how variations of structural and material properties of human intervertebral discs (IVDs) affect the biomechanical responses of the IVDs under simulated physiological loading conditions using a stochastic finite element (SFE) model. An SFE method, which combined an anatomic FE model of human lumbar L3-4 segment and probabilistic analysis of its structural and material properties, was used to generate a dataset of 500 random disc samples with varying structural and material properties. The sensitivity of the biomechanical responses, including intervertebral displacements/rotations, intradiscal pressures (IDP), fiber stresses and matrix strains of annulus fibrosus (AF), were systematically quantified under various physiological loading conditions, including a 500N compression and 7.5Nm moments in the 3 primary rotations. Significant variations of the IDPs, IVD displacements/rotations, and stress/strain distributions were found using the dataset of 500 ramdom disc samples. Under all the loading conditions, the IDPs were positively correlated with the Poisson's ratio of the NP (r=0.46 to 0.75, p=0.004-0.001) and negatively with the Young's modulus of the annulus matrix (r=-0.48 to -0.65, p=0.003-0.001). The primary intervertebral rotations were significantly affected by the Young's modulus of the annulus matrix (r=-0.44 to -0.71, p=0.001-0.032) and the orientations of the annular fibers (r=-0.45 to -0.69, p=0.001-0.029). The heterogeneity of structures and material properties of the IVD had distinct effects on the biomechanical performances of the IVD. These data could help improve our understanding of the intrinsic biomechanics of the IVD and provide references for optimal design of tissue engineered discs by controlling structural and material properties of the disc components.

The biomechanical effects of Ti versus PEEK used in the PLIF surgery on lumbar spine: a finite element analysis

Titanium (Ti) and polyetheretherketone (PEEK) are commonly used in posterior lumbar interbody fusion (PLIF). The study investigated biomechanical effects of Ti versus PEEK used as materials of cage and rods on the lumbar spine. Four different configurations of PLIF were constituted. Stiff Ti rods provided satisfactory initial stability but increased the stress on rods significantly under simulated physiological load conditions. Ti cage increased the stress on bone endplates significantly. Materials of cage and rods had insignificant effects on the nucleus pressure and facet joint force of non-instrumented segments. Further clinical studies and follow-up observations are essential for corroborating these findings.

Modelling the catabolic environment of the moderately degenerated disc with a caprine ex vivo loaded disc culture system.

Low-back pain affects 80 % of the world population at some point in their lives and 40 % of the cases are attributed to intervertebral disc (IVD) degeneration. Over the years, many animal models have been developed for the evaluation of prevention and treatment strategies for IVD degeneration. Ex vivo organ culture systems have also been developed to better control mechanical loading and biochemical conditions, but a reproducible ex vivo model that mimics moderate human disc degeneration is lacking. The present study described an ex vivo caprine IVD degeneration model that simulated the changes seen in the nucleus pulposus during moderate human disc degeneration. Following pre-load under diurnal, simulated physiological loading (SPL) conditions, lumbar caprine IVDs were degenerated enzymatically by injecting collagenase and chondroitinase ABC (cABC). After digestion, IVDs were subjected to SPL for 7 d. No intervention and phosphate-buffered saline injection were used as controls. Disc deformation was continuously monitored to assess disc height recovery. Histology and immunohistochemistry were performed to determine the histological grade of degeneration, matrix expression, degrading enzyme and catabolic cytokine expression. Injection of collagenase and cABC irreversibly affected the disc mechanical properties. A decrease in extracellular matrix components was found, along with a consistent increase in degradative enzymes and catabolic proteins [interleukin (IL)-1β, -8 and vascular endothelial growth factor (VEGF)]. The changes observed were commensurate with those seen in moderate human-IVD degeneration. This model should allow for controlled ex vivo testing of potential biological, cellular and biomaterial treatments of moderate human-IVD degeneration.

Fatigue behavior of subchondral bone under simulated physiological loads of equine athletic training

Fatigue-induced subchondral bone (SCB) injuries are prevalent among athletes due to the repetitive application of high magnitude loads on joints during intense physical training. Existing fatigue studies on bone utilize a standard fatigue test approach by applying loads of a constant magnitude and frequency even though physiological/realistic loading is a combination of various load magnitudes and frequencies. Metal materials in implant and aerospace applications have been studied for fatigue behavior under physiological or realistic loading, however, no such study has been conducted on biological materials like bones. In this study, we investigated fatigue behavior of SCB under the range of loads likely to occur during a fast-workout of an equine athlete in training.A loading protocol was developed by simulating physiological loads occurring during a fast-workout of a racehorse in training, which consisted of a sequence of compression-compression load cycles, including a warm-up (32, 54, 61 MPa) and cool-down (61, 54, 32 MPa) before and after the slow/fast/slow gallop phase of training, also referred to as a training loop. This loading protocol/training loop was applied at room temperature in load-control mode to cylindrical SCB specimens (n = 12) harvested from third metacarpal medial condyles (MCIII) of twelve thoroughbred racehorses and repeated until fatigue failure. The mean ± standard deviation for total time-to-failure (TTF) was 76,393 ± 64,243 s (equivalent to 18.3 ± 15.7 training workouts) for n = 12 specimens. We observed the highest relative energy loss (REL, hysteresis loss normalized to energy absorbed in a load cycle) under loads equivalent to gallop speeds and all specimens failed under these gallop loads. This demonstrates the importance of the gallop speeds in the development of SCB injury, consistent with observations made in live racehorses. Moreover, specimens with higher mean REL and lower mean stiffness during the first loop had a shorter fatigue life which further confirms the detrimental effect of high energy loss in SCB. Further studies are required to reconcile our results with fatigue injuries among equine athletes and understand the influence of different training programs on the fatigue behavior of subchondral bone.

Non-invasive Electroarthrography Measures Load-Induced Cartilage Streaming Potentials via Electrodes Placed on Skin Surrounding an Articular Joint.

We aimed to demonstrate that electroarthrography (EAG) measures streaming potentials originating in the cartilage extracellular matrix during load bearing through electrodes adhered to skin surrounding an articular joint. Equine metacarpophalangeal joints were subjected to simulated physiological loads while (1) replacing synovial fluid with immersion buffers of different electrolyte concentrations and (2) directly degrading cartilage with trypsin. An inverse relationship between ionic strength and EAG coefficient was detected. Compared to native synovial fluid, EAG coefficients increased (P < 0.05) for 5 of 6 electrodes immersed in 0.1X phosphate-buffered saline (PBS) (0.014 M NaCl), decreased (P < 0.05) for 4 of 6 electrodes in 1X PBS (0.14 M NaCl), and decreased (P < 0.05) for all 6 electrodes in 10X PBS (1.4 M NaCl). This relationship corresponds to similar studies where streaming potentials were directly measured on cartilage. EAG coefficients, obtained after trypsin degradation, were reduced (P < 0.05) in 6 of 8, and 7 of 8 electrodes, during simulated standing and walking, respectively. Trypsin degradation was confirmed by direct cartilage assessments. Streaming potentials, measured by directly contacting cartilage, indicated lower cartilage stiffness (P < 10-5). Unconfined compression data revealed reduced Em, representing proteoglycan matrix stiffness (P = 0.005), no change in Ef, representing collagen network stiffness (P = 0.15), and no change in permeability (P = 0.24). Trypsin depleted proteoglycan as observed by both dimethylmethylene blue assay (P = 0.0005) and safranin-O stained histological sections. These data show that non-invasive EAG detects streaming potentials produced by cartilage during joint compression and has potential to become a diagnostic tool capable of detecting early cartilage degeneration.

Biomechanical analysis of combination Ti/PEEK fusion cage designed with topology optimization

Fusion cage has been used in lumbar fusion procedure to treat degenerative disc disorders for decades. To address the drawback of Titanium (Ti) and polyetheretherketone (PEEK) cage, a combination Ti/PEEK cage was proposed in present study. Topology optimization was performed to tailor the topological structure of Ti/PEEK cage. The biomechanical performance was comprehensively assessed using finite element method under simulated physiological load conditions. The volume of optimized cage was reduced by 9.7%. The increased volume for bone graft might improve the fusion performance. The lower peak stress was observed on superior and inferior bone endplates of Ti/PEEK cage model, which reduced the risk of cage subsidence. Meanwhile, Ti/PEEK cage effectively reduced the stress shielding effect associated with over-stiffness of Ti cage. In conclusion, the combination Ti/PEEK cage might be a better choice for fusion surgery in relation to Ti or PEEK cage.

The Effects of Hind Limb Suspension and Cast Mediated Immobilization on Bone Strength Properties.

Astronauts and patients on bedrest are subject to a combination of bone strength losses and muscle atrophy due to microgravity and unloading. In this study, mice were subject to both hind limb suspension and cast mediated immobilization. Pre-treatment and post-treatment microCT scans were utilized to create finite element models. Both pre-treatment and posttreatment scans were then cropped, rotated and threedimensional image registration was performed to eliminate inconsistency in alignment. A hexahedral finite element mesh was then generated from this 3D data. Finite element analysis was conducted to perform simulated physiological loading of the femoral neck to assess bone strength through bone structural morphology. Hind limb suspension combined with Cast Mediated Immobilization caused a 7.9% decrease in bone FEA stiffness compared to the in-vivo pre-treatment control. No differences were found in bone volume or structural efficiency.

Modeling Space Radiation Induced Bone Changes in Rat Femurs through Finite Element Analysis.

As the duration of manned missions outside of the Earth's protective shielding increase, astronauts are at risk for exposure to space radiation. Various organ systems may be damaged due to exposure. This study investigates the bone strength changes using finite element modeling of Long Evans rats (n=85) subjected to graded, head-only proton (0, 10, 25, and 100 cGy, 150 MeV/n) and 28silicon (0, 10, 25, and 50 cGy, 300 MeV/n) radiation. The strength of the femoral neck will be examined due its clinical relevance to hip fractures. It has been shown in previous studies that bone mineral density was not reduced at the site of fracture. These findings question whether measurements of bone mineral density may be used to assess risk of hip fracture. The mechanisms leading to the irregular relationship between bone density and strength are still uncertain within literature and investigated to greater extent in clinical applications. Finite element analysis within this study simulated physiological loading of the femoral neck. No significant changes in femoral neck strength were found across doses of proton or 28silicon head-only radiation. Future work includes performing mechanical testing of the bone samples. Moving from mouse to larger animal models may also provide the increased lifespan for assessing the long-term outcomes of radiation exposure.

Changes in Intervertebral Disk Mechanical Behavior During Early Degeneration.

Intervertebral disk (IVD) degeneration is commonly described by loss of height and hydration. However, in the first stage of IVD degeneration, this loss has not yet occurred. In the current study, we use an ex vivo degeneration model to analyze the changes in IVDs mechanical behavior in the first phase of degeneration. We characterize these changes by stretched-exponential fitting, and suggest the fitted parameters as markers for early degeneration. Enzymatic degeneration of healthy lumbar caprine IVDs was induced by injecting 100 μL of Chondroïtinase ABC (Cabc) into the nucleus. A no-intervention and phosphate buffered saline (PBS) injected group were used as controls. IVDs were cultured in a bioreactor for 20 days under diurnal, simulated-physiological loading (SPL) conditions. Disk deformation was continuously monitored. Changes in disk height recovery behavior were quantified using stretched-exponential fitting. Disk height, histological sections, and water- and glycosaminoglycan (GAG)-content measurements were used as gold standards for the degenerative state. Cabc injection caused significant GAG loss from the nucleus and had detrimental effects on poro-elastic mechanical properties of the IVDs. These were progressive over time, with a propensity toward more linear recovery behavior. On histological sections, both PBS and Cabc injected IVDs showed moderate degeneration. A small GAG loss yields changes in IVD recovery behavior, which can be quantified with stretched-exponential fitting. Parameters changed significantly compared to control. Studies on disk degeneration and biomaterial engineering for degenerative disk disease (DDD) could benefit from focusing on IVD biomechanical behavior rather than height and water-content, as a marker for early disk degeneration.

Supraphysiological loading induces osteocyte-mediated osteoclastogenesis in a novel in vitro model for bone implant loosening.

We aimed to develop an in vitro model for bone implant loosening, allowing analysis of biophysical and biological parameters contributing to mechanical instability-induced osteoclast differentiation and peri-implant bone loss. MLO-Y4-osteocytes were mechanically stimulated for 1 h by fluid shear stress using regimes simulating: (i) supraphysiological loading in the peri-prosthetic interface (2.9 ± 2.9 Pa, 1 Hz, square wave); (ii) physiologic loading in the cortical bone (0.7 ± 0.7 Pa, 5 Hz, sinusoidal wave); and (iii) stress shielding. Cellular morphological parameters, membrane-bound RANKL expression, gene expression influencing osteoclast differentiation, nitric oxide release and caspase 3/7-activity were determined. Either Mouse bone marrow cells were cultured on top of loaded osteocytes or osteocyte-conditioned medium was added to bone marrow cells. Osteoclast differentiation was assessed after 6 days. We found that osteocytes subjected to supraphysiological loading showed similar morphology and caspase 3/7-activity compared to simulated physiological loading or stress shielding. Supraphysiological stimulation of osteocytes enhanced osteoclast differentiation by 1.9-fold compared to physiological loading when cell-to-cell contact was permitted. In addition, it enhanced the number of osteoclasts using conditioned medium by 1.7-fold, membrane-bound RANKL by 3.3-fold, and nitric oxide production by 3.2-fold. The stimulatory effect of supraphysiological loading on membrane-bound RANKL and nitric oxide production was higher than that achieved by stress shielding. In conclusion, the in vitro model developed recapitulated the catabolic biological situation in the peri-prosthetic interface during instability that is associated with osteoclast differentiation and enhanced RANKL expression. The model thus provides a platform for pre-clinical testing of pharmacological interventions with potential to stop instability-induced bone implant loosening. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1425-1434, 2018.

Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation.

IntroductionLumbar hernias occur mostly in the posterolateral region of IVDs and mechanical loading is an important risk factor. Studies show that dynamic and static overloading affect the nucleus and annulus of the IVD differently. We hypothesize there is also variance in the effect of overloading on the IVD’s anterior, lateral and posterior annulus, which could explain the predilection of herniations in the posterolateral region. We assessed the regional mechanical and cellular responses of lumbar caprine discs to dynamic and static overloading.Material and methodsIVDs (n = 125) were cultured in a bioreactor and subjected to simulated-physiological loading (SPL), high dynamic (HD), or high static (HS) overloading. The effect of loading was determined in five disc regions: nucleus, inner-annulus and anterior, lateral and posterior outer-annulus. IVD height loss and external pressure transfer during loading were measured, cell viability was mapped and quantified, and matrix integrity was assessed.ResultsDuring culture, overloaded IVDs lost a significant amount of height, yet the distribution of axial pressure remained unchanged. HD loading caused cell death and disruption of matrix in all IVD regions, whereas HS loading particularly affected cell viability and matrix integrity in the posterior region of the outer annulus.ConclusionAxial overloading is detrimental to the lumbar IVD. Static overloading affects the posterior annulus more strongly, while the nucleus is relatively spared. Hence, static overloading predisposes the disc for posterior herniation. These findings could have implications for working conditions, in particular of sedentary occupations, and the design of interventions aimed at prevention and treatment of early intervertebral disc degeneration.