Differential behaviour of cationic triphenylamine derivatives in fixed and living cells: triggering and imaging cell death.

Triphenylamines are on/off fluorescent DNA minor groove binders, allowing nuclear staining of fixed cells. By contrast, they accumulate in the cytoplasm of living cells and efficiently trigger cell apoptosis upon prolonged visible light irradiation. This process occurs concomitantly with their subcellular re-localization to the nucleus, enabling fluorescence imaging of apoptosis.

The biomechanics of plate fixation of periprosthetic femoral fractures near the tip of a total hip implant: cables, screws, or both?

Femoral shaft fractures after total hip arthroplasty (THA) remain a serious problem, since there is no optimal surgical repair method. Virtually all studies that examined surgical repair methods have done so clinically or experimentally. The present study assessed injury patterns computationally by developing three-dimensional (3D) finite element (FE) models that were validated experimentally. The investigation evaluated three different constructs for the fixation of Vancouver B1 periprosthetic femoral shaft fractures following THA. Experimentally, three bone plate repair methods were applied to a synthetic femur with a 5 mm fracture gap near the tip of a total hip implant. Repair methods were identical distal to the fracture gap, but used cables only (construct A), screws only (construct B), or cables plus screws (construct C) proximal to the fracture gap. Specimens were oriented in 15 degrees adduction to simulate the single-legged stance phase of walking, subjected to 1000 N of axial force, and instrumented with strain gauges. Computationally, a linearly elastic and isotropic 3D FE model was developed to mimic experiments. Results showed excellent agreement between experimental and FE strains, yielding a Pearson linearity coefficient, R2, of 0.92 and a slope for the line of best data fit of 1.06. FE-computed axial stiffnesses were 768 N/mm (construct A), 1023 N/mm (construct B), and 1102 N/mm (construct C). FE surfaces stress maps for cortical bone showed Von Mises stresses, excluding peaks, of 0-8 MPa (construct A), 0-15 MPa (construct B), and 0-20 MPa (construct C). Cables absorbed the majority of load, followed by the plates and then the screws. Construct A yielded peak stress at one of the empty holes in the plate. Constructs B and C had similar bone stress patterns, and can achieve optimal fixation.

The biomechanics of plate repair of periprosthetic femur fractures near the tip of a total hip implant: the effect of cable-screw position.

Optimal surgical positioning of cable-screw pairs in repairing periprosthetic femur fractures near the tip of a total hip implant still remains unclear. No studies in the literature to date have developed a fully three-dimensional finite element (FE) model that has been validated experimentally to assess these injury patterns. The aim of the present study was to evaluate the biomechanical performance of three different implant-bone constructs for the fixation of periprosthetic femoral shaft fractures following total hip arthroplasty. Experimentally, three bone-plate repair configurations were applied to the periprosthetic synthetic femur fractured with a 5 mm gap near the tip of a total hip implant. Constructs A, B, and C, respectively, had successively larger distances between the most proximal and the most distal cable-screw pairs used to affix the plate. Specimens were oriented in 15 degrees adduction, subjected to 1000 N of axial force to simulate the single-legged stance phase of walking, and instrumented with strain gauges. Computationally, a linearly elastic and isotropic three-dimensional FE model was developed to mimic the experimental setup. Results showed excellent agreement between experimental versus FE analysis strains, yielding a Pearson linearity coefficient, R2, of 0.90 and a slope for the line of best data fit of 0.96. FE axial stiffnesses were 601 N/mm (Construct A), 849 N/mm (Construct B), and 1359 N/mm (Construct C). FE surface stress maps for cortical bone showed maximum von Mises values of 74 MPa (Construct A), 102 MPa (Construct B), and 57 MPa (Construct C). FE stress maps for the metallic components showed minimum von Mises values for Construct C, namely screw (716MPa), cable (445MPa), plate (548MPa), and hip implant (154MPa). In the case of good bone stock, as modelled by the present synthetic femur model, optimal fixation can be achieved with Construct C.

Computation of bone remodelling after Duracon knee arthroplasty using a thermodynamic-based model.

The present study utilizes a recently developed literature model for the bone remodelling process to predict the evolution of bone density following Duracon total knee arthroplasty (TKA). In this model, which is based on chemical kinetics and irreversible thermodynamics, bone is treated as a self-organizing system capable of exchanging matter, energy, and entropy with its surroundings. Unlike previous models in which mechanical loading is regarded as the only stimulus for bone remodelling, the present model establishes a unique coupling between mechanical loading and the chemical reactions involved in the process of bone remodelling. This model was incorporated into the finite element software ANSYS by means of a macro to compute density distribution in distal femoral bone both before and after TKA. Consistent with dual-energy X-ray absorptiometry (DEXA) scans reported in the literature, the results showed that the most severe bone loss occurs in the anterior region of the distal femur and that there is more bone resorption in the lateral than the medial condyle following TKA. Furthermore, the bone density distribution predicted using the present model showed a gradual and uniform pattern and thus a more realistic bone evolution contrary to the strain energy density model, where there is no gradual bone density evolution.

The biomechanical effect of changes in cancellous bone density on synthetic femur behaviour.

Biomechanical researchers increasingly use commercially available and experimentally validated synthetic femurs to mimic human femurs. However, the choice of cancellous bone density for these artificial femurs appears to be done arbitrarily. The aim of the work reported in this paper was to examine the effect of synthetic cancellous bone density on the mechanical behaviour of synthetic femurs. Thirty left, large, fourth-generation composite femurs were mounted onto an Instron material testing system. The femurs were divided evenly into five groups each containing six femurs, each group representing a different synthetic cancellous bone density: 0.08, 0.16, 0.24, 0.32, and 0.48 g/cm3. Femurs were tested non-destructively to obtain axial, lateral, and torsional stiffness, followed by destructive tests to measure axial failure load, displacement, and energy. Experimental results yielded the following ranges and the coefficient of determination for a linear regression (R2) with cancellous bone density: axial stiffness (range 2116.5-2530.6N/mm; R2 = 0.94), lateral stiffness (range 204.3-227.8N/mm; R2 = 0.08), torsional stiffness (range 259.9-281.5N/mm; R2 = 0.91), failure load (range 5527.6-11 109.3 N; R2 = 0.92), failure displacement (range 2.97-6.49 mm; R2 = 0.85), and failure energy (range 8.79-42.81 J; R2 = 0.91). These synthetic femurs showed no density effect on lateral stiffness and only a moderate influence on axial and torsional stiffness; however, there was a strong density effect on axial failure load, displacement, and energy. Because these synthetic femurs have previously been experimentally validated against human femurs, these trends may be generalized to the clinical situation. This is the first study in the literature to perform such an assessment.

The biomechanics of a validated finite element model of stress shielding in a novel hybrid total knee replacement.

This study proposes a novel hybrid total knee replacement (TKR) design to improve stress transfer to bone in the distal femur and, thereby, reduce stress shielding and consequent bone loss. Three-dimensional finite element (FE) models were developed for a standard and a hybrid TKR and validated experimentally. The Duracon knee system (Stryker Canada) was the standard TKR used for the FE models and for the experimental tests. The FE hybrid device was identical to the standard TKR, except that it had an interposing layer of carbon fibre-reinforced polyamide 12 lining the back of the metallic femoral component. A series of experimental surface strain measurements were then taken to validate the FE model of the standard TKR at 3000 N of axial compression and at 0 degreeof knee flexion. Comparison of surface strain values from FE analysis with experiments demonstrated good agreement, yielding a high Pearson correlation coefficient of R(2)= 0.94. Under a 3000N axial load and knee flexion angles simulating full stance (0O degree, heel strike (200 degrees, and toe off (600 degrees during normal walking gait, the FE model showed considerable changes in maximum Von Mises stress in the region most susceptible to stress shielding (i.e. the anterior region, just behind the flange of the femoral implant). Specifically, going from a standard to a hybrid TKR caused an increase in maximum stress of 87.4 per cent (O0 degree from 0.15 to 0.28 MPa), 68.3 per cent (200 degrees from 1.02 to 1.71 MPa), and 12.6 per cent (600 degrees from 2.96 to 3.33 MPa). This can potentially decrease stress shielding and subsequent bone loss and knee implant loosening. This is the first report to propose and biomechanically to assess a novel hybrid TKR design that uses a layer of carbon fibrereinforced polyamide 12 to reduce stress shielding.

The effect of cortex thickness on intact femur biomechanics: a comparison of finite element analysis with synthetic femurs.

Biomechanical studies on femur fracture fixation with orthopaedic implants are numerous in the literature. However, few studies have compared the mechanical stability of these repair constructs in osteoporotic versus normal bone. The present aim was to examine how changes in cortical wall thickness of intact femurs affect biomechanical characteristics. A three-dimensional, linear, isotropic finite element (FE) model of an intact femur was developed in order to predict the effect of bicortical wall thickness, t, relative to the femur's mid-diaphyseal outer diameter, D, over a cortex thickness ratio range of 0 < or = t/D < or = 1. The FE model was subjected to loads to obtain axial, lateral, and torsional stiffness. Ten commercially available synthetic femurs were then used to mimic 'osteoporotic' bone with t/D = 0.33, while ten synthetic left femurs were used to simulate 'normal' bone with t/D = 0.66. Axial, lateral, and torsional stiffness were measured for all femurs. There was excellent agreement between FE analysis and experimental stiffness data for all loading modes with an aggregate average percentage difference of 8 per cent. The FE results for mechanical stiffness versus cortical thickness ratio (0 < or = t/D < or = 1) demonstrated exponential trends with the following stiffness ranges: axial stiffness (0 to 2343 N/mm), lateral stiffness (0 to 62 N/mm), and torsional stiffness (0 to 198 N/mm). This is the first study to characterize mechanical stiffness over a wide range of cortical thickness values. These results may have some clinical implications with respect to appropriately differentiating between older and younger human long bones from a mechanical standpoint.

The effect of the screw pull-out rate on cortical screw purchase in unreamed and reamed synthetic long bones.

Orthopaedic fracture fixation constructs are typically mounted on to human long bones using cortical screws. Biomechanical studies are increasingly employing commercially available synthetic bones. The aim of this investigation was to examine the effect of the screw pull-out rate and canal reaming on the cortical bone screw purchase strength in synthetic bone. Cylinders made of synthetic material were used to simulate unreamed (foam-filled) and reamed (hollow) human long bone with an outer diameter of 35 mm and a cortex wall thickness of 4 mm. The unreamed and reamed cylinders each had 56 sites along their lengths into which orthopaedic cortical bone screws (major diameter, 3.5 mm) were inserted to engage both cortices. The 16 test groups (n = 7 screw sites per group) had screws extracted at rates of 1 mm/ min, 5 mm/min, 10 mm/min, 20 mm/min, 30 mm/min, 40 mm/min, 50 mm/min, and 60 mm/ min. The failure force and failure stress increased and were highly linearly correlated with pull-out rate for reamed (R2 = 0.60 and 0.60), but not for unreamed (R2 = 0.00 and 0.00) specimens. The failure displacement and failure energy were relatively unchanged with pull-out rate, yielding low coefficients for unreamed (R2 = 0.25 and 0.00) and reamed (R2 = 0.27 and 0.00) groups. Unreamed versus reamed specimens were statistically different for failure force (p = 0.000) and stress (p = 0.000), but not for failure displacement (p = 0.297) and energy (0.054 < p < 1.000). This is the first study to perform an extensive investigation of the screw pull-out rate in unreamed and reamed synthetic long bone.

The biomechanics of the T2 femoral nailing system: a comparison of synthetic femurs withfinite element analysis.

Intramedullary nails are commonly used to repair femoral fractures. Fractures in normal healthy bone often occur in the young during motor vehicle accidents. Although clinically beneficial, bone refracture and implant failure persist. Large variations in human femur quality and geometry have motivated recent experimental use of synthetic femurs that mimic human tissue and the development of increasingly sophisticated theoretical models. Four synthetic femurs were fitted with a T2 femoral nailing system (Stryker, Mahwah, New Jersey, USA). The femurs were not fractured in order to simulate post-operative perfect union. Six configurations were created: retrograde nail with standard locking (RS), retrograde nail with advanced locking 'off' (RA-off), retrograde nail with advanced locking 'on' (RA-on), antegrade nail with standard locking (AS), antegrade nail with advanced locking 'off' (AA-off), and antegrade nail with advanced locking 'on' (AA-on). Strain gauges were placed on the medial side of femurs. A 580 N axial load was applied, and the stiffness was measured. Strains were recorded and compared with results from a three-dimensional finite element (FE) model. Experimental axial stiffnesses for RA-off (771.3 N/mm) and RA-on (681.7 N/mm) were similar to intact human cadaveric femurs from previous literature (757 + 264 N/mm). Conversely, experimental axial stiffnesses for AS (1168.8N/mm), AA-off (1135.3N/mm), AA-on (1152.1 N/mm), and RS (1294.0 N/mm) were similar to intact synthetic femurs from previous literature (1290 +/- 30 N/mm). There was better agreement between experimental and FE analysis strains for RS (average percentage difference, 11.6 per cent), RA-on (average percentage difference, 11.1 per cent), AA-off (average percentage difference, 13.4 per cent), and AA-on (average percentage difference, 16.0 per cent), than for RA-off (average percentage difference, 33.5 per cent) and AS (average percentage difference, 32.6 per cent). FE analysis was more predictive of strains in the proximal and middle sections of the femur-nail construct than the distal. The results mimicked post-operative clinical stability at low static axial loads once fracture healing begins to occur.

Cancellous bone screw purchase: a comparison of synthetic femurs, human femurs, and finite element analysis.

Biomechanical assessments of orthopaedic fracture fixation constructs are increasingly using commercially available analogues such as the fourth-generation composite femur (4GCF). The aim of this study was to compare cancellous screw purchase directly between these surrogates and human femurs, which has not been done previously. Synthetic and human femurs each had one orthopaedic cancellous screw (major diameter, 6.5 mm) inserted along the femoral neck axis and into the spongy bone of the femoral head to a depth of 30 mm. Screws were removed to obtain pull-out force, shear stress, and energy values. The three experimental study groups (n = 6 femurs each) were the 4GCF with a 'solid' cancellous matrix, the 4GCF with a 'cellular' cancellous matrix, and human femurs. Moreover, a finite element model was developed on the basis of the material properties and anatomical geometry of the two synthetic femurs in order to assess cancellous screw purchase. The results for force, shear stress, and energy respectively were as follows: 4GCF solid femurs, 926.47 +/- 66.76 N, 2.84 +/- 0.20 MPa, and 0.57 +/- 0.04 J; 4GCF cellular femurs, 1409.64 +/- 133.36 N, 4.31 +/- 0.41 MPa, and 0.99 +/- 0.13 J; human femurs, 1523.29 +/- 1380.15N, 4.66 +/- 4.22 MPa, and 2.78 +/- 3.61J. No statistical differences were noted when comparing the three experimental groups for pull-out force (p = 0.413), shear stress (p = 0.412), or energy (p = 0.185). The 4GCF with either a 'solid' or 'cellular' cancellous matrix is a good biomechanical analogue to the human femur at the screw thread-bone interface. This is the first study to perform a three-way investigation of cancellous screw purchase using 4GCFs, human femurs, and finite element analysis.