Ex vivo biomechanical evaluation of 2.4 mm LCP plate rod constructs versus 2.7 mm LCP applied to the feline tibia.

OBJECTIVE: To compare the stiffness and strength of three plate and rod fixation constructs applied to a feline tibial gap model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Thirty-three unpaired tibiae obtained from skeletally mature cats. METHODS: The tibiae were randomly divided into three groups. The following implants were then applied to the feline tibiae prior to the creation of a 10 mm diaphyseal gap. Group 1: 2.4 mm locking compression plate (LCP) and 1.0 mm intramedullary pin (IMP). Group 2: 2.4 mm LCP and 1.6 mm IMP. Group 3: 2.7 mm LCP. Subsequently, each specimen was tested for torsion, axial compression, and axial load until construct failure. Student's t-tests were used to compare the torsional and axial stiffness, yield load, and maximum axial force. RESULTS: Group 2 had higher axial stiffness than group 3 (p = .013). Group 1 showed a lower maximum axial force and yield point than groups 2 and 3 (p < .01; p < .05, respectively). There were no among-group differences in torsional stiffness. CONCLUSION: Constructs with a 2.4 mm LCP and 1.6 mm IMP provided the strongest and most rigid constructs in a feline tibia gap model. CLINICAL SIGNIFICANCE: A plate-rod construct combining a 2.4 mm LCP and a 1.6 mm IMP is appropriate for achieving high implant stiffness and resisting maximum axial force in treatment of tibial fractures in cats.

Physiological stretching induces a differential extracellular matrix gene expression response in acetabular labrum cells.

The acetabular labrum is a fibrocartilaginous ring surrounding the acetabulum and is important for hip stability and contact pressure dissipation through a sealing function. Injury of the labrum may contribute to hip-joint degeneration and development of secondary osteoarthritis. Understanding how extracellular matrix (ECM) production and remodelling is regulated is of key importance for successful tissue restoration. The present study hypothesised that physiological stretching enhanced the metabolic activity and altered the ECM gene expression in labrum cells. Primary bovine labrum cells were physiologically stretched for up to 5 d. 24 h after the last stretch cycle, changes in metabolic activity were measured using the PrestoBlue™ HS Cell Viability Reagent and ECM gene expression was examined using the quantitative polymerase chain reaction method. Targets of interest were further investigated using immunofluorescence and enzyme-linked immunosorbent assay. Metabolic activity was not affected by the stretching (0.9746 ± 0.0614, p > 0.05). Physiological stretching upregulated decorin (DCN) (1.8548 ± 0.4883, p = 0.002) as well as proteoglycan 4 (PRG4) (1.7714 ± 0.6600, p = 0.029) and downregulated biglycan (BGN) (0.7018 + 0.1567, p = 0.008), cartilage oligomeric matrix protein (COMP) (0.5747 ± 0.2650, p = 0.029), fibronectin (FN1) (0.5832 ± 0.0996, p < 0.001) and spondin 1 (SPON1) (0.6282 ± 0.3624, p = 0.044) gene expression. No difference in PRG4 and DCN abundance or release could be measured. The here identified mechanosensitive targets are known to play relevant roles in tissue organisation. Therefore, physiological stretching might play a role in labrum tissue homeostasis and regeneration.

Patient characteristics affect hip contact forces during gait.

OBJECTIVE: To examine hip contact force (HCF), calculated through multibody modelling, in a large total hip replacement (THR) cohort stratified by patient characteristics such as body mass index (BMI), age and function. METHOD: 132 THR patients undertook one motion capture session of gait analysis at a self-selected walking speed. HCFs were then calculated using the AnyBody Modelling System. Patients were stratified into three BMI groups, five age groups, and finally three functional groups determined by their self-selected gait speed. By means of statistical parametric mapping (SPM), statistical analyses of the 1-dimensional time series were performed to separately evaluate the influence of age, BMI and functionality on HCF. RESULTS: The mean predicted HCFs were comparable to HCFs measured with instrumented prostheses reported in the literature. The SPM analysis revealed a statistically significant positive linear correlation between BMI and HCF, indicating that obese patients are more likely to experience higher HCF during most of the stance phase, while a statistically significant negative correlation with age was found only during the late swing-phase. Patients with higher functional ability exhibited significantly increased peak HCF, while patients with lower functional ability demonstrated lower HCFs overall and a pathological flattening of the typical double hump force profile. CONCLUSION: HCFs experienced at the bearing surface are highly dependent on patient characteristics. BMI and functional ability were determined to have the biggest influence on contact forces. Current preclinical testing standards do not reflect this.

Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model.

Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

The role of endplate poromechanical properties on the nutrient availability in the intervertebral disc.

OBJECTIVE: To investigate the relevance of the human vertebral endplate poromechanics on the fluid and metabolic transport from and to the intervertebral disc (IVD) based on educated estimations of the poromechanical parameter values of the bony endplate (BEP). METHODS: 50 micro-models of different BEP samples were generated from µCTs of lumbar vertebrae and allowed direct determination of porosity values. Permeability values were calculated by using the micro-models, through the simulation of permeation via computational fluid dynamics. These educated ranges of porosity and permeability values were used as inputs for mechano-transport simulations to assess their effect on both the distributions of metabolites within an IVD model and the poromechanical calculations within the cartilaginous part of the endplate i.e., the cartilage endplate (CEP). RESULTS: BEP effective permeability was highly correlated to local variations of porosity (R(2) ≈ 0.88). Universal patterns between bone volume fraction and permeability arose from these results and from other experimental data in the literature. These variations in BEP permeability and porosity had negligible effects on the distributions of metabolites within the disc. In the CEP, the variability of the poromechanical properties of the BEP did not affect the predicted consolidation but induced higher fluid velocities. CONCLUSIONS: The present paper provides the first sets of thoroughly identified BEP parameter values that can be further used in patient-specific poromechanical studies. Representing BEP structural changes through variations in poromechanical properties did not affect the diffusion of metabolites. However, attention might be paid to alterations in fluid velocities and cell mechano-sensing within the CEP.

Epigallocatechin 3-gallate suppresses interleukin-1ß-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats.

Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1ß, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB.

Challenges and strategies in the repair of ruptured annulus fibrosus.

Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell- and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.

Osseointegration of biochemically modified implants in an osteoporosis rodent model.

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), peri-implant bone area (BA), bone volume/tissue volume (BV/TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

Nanofiber membranes as biomimetic and mechanically stable surface coatings.

Elastomers have been extensively exploited to study cell physiology in fields such as mechanobiology, however, their intrinsic high hydrophobicity renders their surfaces incompatible for prolonged cell adhesion and proliferation. Electrospun fiber networks on the other side provide a promising environment for enhanced cell adhesion and growth due to their architecture closely mimicking the structure of the extracellular matrix present within tissues of the human body. Here, we explored the stable integration of electrospun fibers onto the surfaces of elastomeric materials to promote cytocompatibility of these composites. Elastomers based on room temperature vulcanizing silicone (RTV), polydimethylsiloxane (PDMS) as well as functionalized PDMS-based materials were chosen as wafer substrates for attachment of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDFhfp) fibers, a well-known antithrombotic polymer. Electrospinning the fibers onto uncured interfaces acted as bonding agents on the wafers, enabling penetration and formation of a stable bond between the fibers surfaces and the elastomers after curing the interface. Dimensional analysis revealed a relationship between peeling force, intrusion depth and the elastic modulus of the wafers. A design parameter Πα was extrapolated to be used as a predictive tool of the peeling force when intrusion depth of PVDFhfp fibers and elastic modulus of the wafers are known. Cultivating fibroblasts on these hybrid membranes showed cell attachment and growth over 7 days regardless of the composition of the substrate, confirming high cytocompatibility for all composite materials. The presented approach opens avenues to establish nanofiber morphologies as a novel, stable surface texturing tool for tissue engineering, cell biology, medical devices and textiles.

Lateral stability in healthy proximal interphalangeal joints versus surface replacement and silicone arthroplasty: Results of a three-dimensional motion analysis study.

The objective of this study was to quantify the lateral stability of healthy proximal interphalangeal (PIP) joints using a three-dimensional motion capture system and compare it to affected joints after surface replacement or silicone arthroplasty. Three study groups comprised healthy participants, patients with PIP joint osteoarthritis treated with a surface replacing implant (CapFlex-PIP) and those with a silicone arthroplasty. All participants were matched on gender and finger, and the two patient groups were also matched on length of follow-up. An optical tracking system was used to measure lateral stability. Radial and ulnar stability of the PIP joint was measured as the maximal lateral deviation angle of the middle phalanx under loads of 40 g, 90 g and 170g at 0°, 20° and 45° PIP joint flexion. Measurement reliability was evaluated with a test-retest trial [intraclass correlation coefficient (ICC)]. A total of 30 joints were assessed with 5 index and 5 middle fingers per test group. Lateral deviation increased proportionally with applied weight. Silicone arthroplasty joints had a higher median lateral deviation angle of 5.1° (range 0.7-7.9) than healthy [3.0° (0.5-11.0)] and surface replacement joints [3.3° (0.3-7.4)] at 45° flexion and under 170g load. Test-retest reliability was high with an ICC of 0.93. Lateral PIP joint stability is highly variable in both healthy participants and patients after PIP joint arthroplasty. PIP joint surface replacement arthroplasty tends to achieve better anatomical stability compared to flexible silicone implants.

Differences in endplate deformation of the adjacent and augmented vertebra following cement augmentation.

Vertebral cement augmentation can restore the stiffness and strength of a fractured vertebra and relieve chronic pain. Previous finite element analysis, biomechanical tests and clinical studies have indirectly associated new adjacent vertebral fractures following augmentation to altered loading. The aim of this repeated measures in situ biomechanical study was to determine the changes in the adjacent and augmented endplate deformation following cement augmentation of human cadaveric functional spine units (FSU) using micro-computed tomography (micro-CT). The surrounding soft tissue and posterior elements of 22 cadaveric human FSU were removed. FSU were assigned to two groups, control (n = 8) (loaded on day 1 and day 2) and augmented (n = 14) (loaded on day 1, augmented 20% cement fill, and loaded on day 2). The augmented group was further subdivided into a prophylactic augmentation group (n = 9), and vertebrae which spontaneously fractured during loading on day 1 (n = 5). The FSU were axially loaded (200, 1,000, 1,500-2,000 N) within a custom made radiolucent, saline filled loading device. At each loading step, FSUs were scanned using the micro-CT. Endplate heights were determined using custom software. No significant increase in endplate deformation following cement augmentation was noted for the adjacent endplate (P > 0.05). The deformation of the augmented endplate was significantly reduced following cement augmentation for both the prophylactic and fracture group (P < 0.05, P < 0.01, respectively). Endplate deformation of the controls showed no statistically significant differences between loading on day 1 and day 2. A linear relationship was noted between the applied compressive load and endplate deflection (R (2) = 0.58). Evidence of significant endplate deformation differences between unaugmented and augmented FSU, while evident for the augmented endplate, was not present for the adjacent endplate. This non-invasive micro-CT method may also be useful to investigate endplate failure, and parameters that predict vertebral failure.

Contrasting routes of c-type cytochrome assembly in mitochondria, chloroplasts and bacteria.

The biogenesis of bacterial c-type cytochromes generally involves many gene products--some of which may also have roles in other processes--and their interaction with the disulphide-bond-forming system of the bacterial periplasm. However, in some bacteria a simpler process appears to operate that might be related to the formation of c-type cytochromes in thylakoids of photosynthetic cells. The corresponding process in fungal mitochondria is distinct.

Biofidelic finite element models for accurately classifying hip fracture in a retrospective clinical study of elderly women from the AGES Reykjavik cohort.

Clinical retrospective studies have only reported limited improvements in hip fracture classification accuracy using finite element (FE) models compared to conventional areal bone mineral density (aBMD) measurements. A possible explanation is that state-of-the-art quasi-static models do not estimate patient-specific loads. A novel FE modeling technique was developed to improve the biofidelity of simulated impact loading from sideways falling. This included surrogate models of the pelvis, lower extremities, and soft tissue that were morphed based on subject anthropometrics. Hip fracture prediction models based on aBMD and FE measurements were compared in a retrospective study of 254 elderly female subjects from the AGES-Reykjavik study. Subject fragility ratio (FR) was defined as the ratio between the ultimate forces of paired biofidelic models, one with linear elastic and the other with non-linear stress-strain relationships in the proximal femur. The expected end-point value (EEV) was defined as the FR weighted by the probability of one sideways fall over five years, based on self-reported fall frequency at baseline. The change in maximum volumetric strain (ΔMVS) on the surface of the femoral neck was calculated between time of ultimate femur force and 90% post-ultimate force in order to assess the extent of tensile tissue damage present in non-linear models. After age-adjusted logistic regression, the area under the receiver-operator curve (AUC) was highest for ΔMVS (0.72), followed by FR (0.71), aBMD (0.70), and EEV (0.67), however the differences between FEA and aBMD based prediction models were not deemed statistically significant. When subjects with no history of falling were excluded from the analysis, thus artificially assuming that falls were known a priori with no uncertainty, a statistically significant difference in AUC was detected between ΔMVS (0.85), and aBMD (0.74). Multivariable linear regression suggested that the variance in maximum elastic femur force was best explained by femoral head radius, pelvis width, and soft tissue thickness (R2 = 0.79; RMSE = 0.46 kN; p < 0.005). Weighting the hip fracture prediction models based on self-reported fall frequency did not improve the models' sensitivity, however excluding non-fallers lead to significant differences between aBMD and FE based models. These findings suggest that an accurate assessment of fall probability is necessary for accurately identifying individuals predisposed to hip fracture.

Molecular genetics of the genus Paracoccus: metabolically versatile bacteria with bioenergetic flexibility.

Paracoccus denitrificans and its near relative Paracoccus versutus (formerly known as Thiobacilllus versutus) have been attracting increasing attention because the aerobic respiratory system of P. denitrificans has long been regarded as a model for that of the mitochondrion, with which there are many components (e.g., cytochrome aa3 oxidase) in common. Members of the genus exhibit a great range of metabolic flexibility, particularly with respect to processes involving respiration. Prominent examples of flexibility are the use in denitrification of nitrate, nitrite, nitrous oxide, and nitric oxide as alternative electron acceptors to oxygen and the ability to use C1 compounds (e.g., methanol and methylamine) as electron donors to the respiratory chains. The proteins required for these respiratory processes are not constitutive, and the underlying complex regulatory systems that regulate their expression are beginning to be unraveled. There has been uncertainty about whether transcription in a member of the alpha-3 Proteobacteria such as P. denitrificans involves a conventional sigma70-type RNA polymerase, especially since canonical -35 and -10 DNA binding sites have not been readily identified. In this review, we argue that many genes, in particular those encoding constitutive proteins, may be under the control of a sigma70 RNA polymerase very closely related to that of Rhodobacter capsulatus. While the main focus is on the structure and regulation of genes coding for products involved in respiratory processes in Paracoccus, the current state of knowledge of the components of such respiratory pathways, and their biogenesis, is also reviewed.

Determination of vertebral endplate deformation under load using micro-computed tomography.

Endplate strength plays an important role in preventing vertebral failure of normal vertebrae and in cases where surgical intervention has replaced the disc with an implant or has altered the vertebral loading. We have developed a non-contact method based on the principles of image guided failure analysis, mechanical testing, and micro-computed tomography analysis, which allows for in vitro quantification of endplate deformation under axial load. The method allows for the implementation of a repeated measures experimental design, each specimen acting as its own control. Our methodology was validated using cadaveric functional spine units, loaded stepwise from 200 N to a maximum of 2000 N. The loading protocol was repeated over two days, allowing time for recovery of the disc mechanical properties. We found no meaningful difference in measured force, stiffness, and endplate deformation between day 1 and day 2. The mean fiducial registration error was less than 0.015 mm for all three axes. Endplate deformation could be reproducibly estimated. The root mean squared error was 0.03 mm, which is the effective precision of the method. Using this micro-CT based method, the effect of interbody implants, grafts, disc replacement strategies, and surgical procedures such as nucleotomy and vertebral cement augmentation on endplate mechanical behaviour can be ascertained.

Larger vertebral endplate concavities cause higher failure load and work at failure under high-rate impact loading of rabbit spinal explants.

Vertebral fractures are among the most common of all osteoporosis related fracture types and its risk assessment is largely based on bone quality measures. Morphometric parameters are not yet considered, although endplate thickness and concavity shape were found to be important in fracture prediction in low-rate tests. We hypothesized that, under high-rate impact loading, the shape and size of the central endplate concavity are of key importance for fracture prediction. Therefore, we tested rabbit spinal segment explants in vitro under high-rate impact loading. With a combination of microCT to describe endplate morphometry, high-speed video imaging, and impact force measurement, endplate morphometry was correlated to the mechanical response. We found that endplate concavity shape and volume were important in describing the mechanical response: larger concavities caused higher failure load. We suggest a model for the fracture mechanism under high-rate impact loading, considering the morphometry of the endplates: wider and more voluminous concavities are protective whereas steeper slopes of the concavity edges and increasing bone volume fraction of the central endplate moiety are disadvantageous. Therefore, the shape and size of endplate morphometry are important in vertebral fracture prediction and should be considered included in vertebral fracture risk assessment.

Correlating diameter, mechanical and structural properties of poly(l-lactide) fibres from needleless electrospinning.

The development and application of nanofibres requires a thorough understanding of the mechanical properties on a single fibre level including respective modelling tools for precise fibre analysis. This work presents a mechanical and morphological study of poly-l-lactide nanofibres developed by needleless electrospinning. Atomic force microscopy (AFM) and micromechanical testing (MMT) were used to characterise the mechanical response of the fibres within a diameter range of 200-1400 nm. Young's moduli E determined by means of both methods are in sound agreement and show a strong increase for thinner fibres below a critical diameter of 800 nm. Similar increasing trends for yield stress and hardening modulus were measured by MMT. Finite element analyses show that the common practice of modelling three-point bending tests with either double supported or double clamped beams is prone to significant bias in the determined elastic properties, and that the latter is a good approximation only for small diameters. Therefore, an analytical formula based on intermediate boundary conditions is proposed that is valid for the whole tested range of fibre diameters, providing a consistently low error in axial Young's modulus below 10%. The analysis of fibre morphology by differential scanning calorimetry and 2D wide-angle X-ray scattering revealed increasing polymer chains alignment in the amorphous phase and higher crystallinity of fibres for decreasing diameter. The combination of these observations with the mechanical characterisation suggests a linear relationship between Young's modulus and both crystallinity and molecular orientation in the amorphous phase. STATEMENT OF SIGNIFICANCE: Fibrous membranes have rapidly growing use in various applications, each of which comes with specific property requirements. However, the development and production of nanofibre membranes with dedicated mechanical properties is challenging, in particular with techniques suitable for industrial scales such as needleless electrospinning. It is therefore a key step to understand the mechanical and structural characteristics of single nanofibres developed in this process, and to this end, the present work presents changes of internal fibre structure and mechanical properties with diameter, based on dedicated models. Special attention was given to the commonly used models for analyzing Young's modulus of single nanofibers in three-point bending tests, which are shown to be prone to large errors, and an improved robust approach is proposed.

On the Failure Initiation in the Proximal Human Femur Under Simulated Sideways Fall.

The limitations of areal bone mineral density measurements for identifying at-risk individuals have led to the development of alternative screening methods for hip fracture risk including the use of geometrical measurements from the proximal femur and subject specific finite element analysis (FEA) for predicting femoral strength, based on quantitative CT data (qCT). However, these methods need more development to gain widespread clinical applications. This study had three aims: To investigate whether proximal femur geometrical parameters correlate with obtained femur peak force during the impact testing; to examine whether or not failure of the proximal femur initiates in the cancellous (trabecular) bone; and finally, to examine whether or not surface fracture initiates in the places where holes perforate the cortex of the proximal femur. We found that cortical thickness around the trochanteric-fossa is significantly correlated to the peak force obtained from simulated sideways falling (R 2 = 0.69) more so than femoral neck cortical thickness (R 2 = 0.15). Dynamic macro level FE simulations predicted that fracture generally initiates in the cancellous bone compartments. Moreover, our micro level FEA results indicated that surface holes may be involved in primary failure events.

Material mapping strategy to improve the predicted response of the proximal femur to a sideways fall impact.

Sideways falls are largely responsible for the highly prevalent osteoporotic hip fractures in today's society. These injuries are dynamic events, therefore dynamic FE models validated with dynamic ex vivo experiments provide a more realistic simulation than simple quasi-static analysis. Drop tower experiments using cadaveric specimens were used to identify the material mapping strategy that provided the most realistic mechanical response under impact loading. The present study tested the addition of compression-tension asymmetry, tensile bone damage, and cortical-specific strain rate dependency to the material mapping strategy of fifteen dynamic FE models of the proximal femur, and found improved correlations and reduced error for whole bone stiffness (R2 = 0.54, RSME = 0.87kN/mm) and absolute maximum force (R2 = 0.56, RSME =0.57kN), and a high correlation in impulse response (R2 = 0.82, RSME =12.38kg/s). Simulations using fully bonded nodes between the rigid bottom plate and PMMA cap supporting the femoral head had higher correlations and less error than simulations using a frictionless sliding at this contact surface. Strain rates over 100/s were observed in certain elements in the femoral neck and trochanter, indicating that additional research is required to better quantify the strain rate dependencies of both trabecular and cortical bone at these strain rates. These results represent the current benchmark in dynamic FE modeling of the proximal femur in sideways falls. Future work should also investigate improvements in experimental validation techniques by developing better displacement measurements and by enhancing the biofidelity of the impact loading wherever possible.

Proton transfer: it's a stringent process.

Proton transfer into and out of proteins is important, both for many enzyme reaction mechanisms and proton pumping across membranes. Recent work on several proteins has revealed stringent requirements for amino-acid side chains and subtle reorganisation of hydrogen-bond networks involving bound water molecules.