Micromotion-induced peri-prosthetic fluid flow around a cementless femoral stem

Micromotion-induced interstitial fluid flow at the bone-implant interface has been proposed to play an important role in aseptic loosening of cementless implants. High fluid velocities are thought to promote aseptic loosening through activation of osteoclasts, shear stress induced control of mesenchymal stem cells differentiation, or transport of molecules. In this study, our objectives were to characterize and quantify micromotion-induced fluid flow around a cementless femoral stem using finite element modeling. With a 2D model of the bone-implant interface and full-factorial design, we first evaluated the relative influence of material properties, and bone-implant micromotion and gap on fluid velocity. Transverse sections around a femoral stem were built from computed tomography images, while boundary conditions were obtained from experimental measurements on the same femur. In a second step, a 3D model was built from the same data-set to estimate the shear stress experienced by cells hosted in the peri-implant tissues. The full-factorial design analysis showed that local micromotion had the most influence on peak fluid velocity at the interface. Remarkable variations in fluid velocity were observed in the macrostructures at the surface of the implant in the 2D transverse sections of the stem. The 3D model predicted peak fluid velocities extending up to 2.2 mm/s in the granulation tissue and to 3.9 mm/s in the trabecular bone. Peak shear stresses on the cells hosted in these tissues ranged from 0.1 to 12.5 Pa. These results offer insight into mechanical stimuli encountered at the bone-implant interface.     

The genome as a life-history character: why rate of molecular evolution varies between mammal species

DNA sequences evolve at different rates in different species. This rate variation has been most closely examined in mammals, revealing a large number of characteristics that can shape the rate of molecular evolution. Many of these traits are part of the mammalian life-history continuum: species with small body size, rapid generation turnover, high fecundity and short lifespans tend to have faster rates of molecular evolution. In addition, rate of molecular evolution in mammals might be influenced by behaviour (such as mating system), ecological factors (such as range restriction) and evolutionary history (such as diversification rate). I discuss the evidence for these patterns of rate variation, and the possible explanations of these correlations. I also consider the impact of these systematic patterns of rate variation on the reliability of the molecular date estimates that have been used to suggest a Cretaceous radiation of modern mammals, before the final extinction of the dinosaurs.     

The influence of different surface treatments on the primary stability of cementless acetabular cups: an in vitro study]

INTRODUCTION: Long-term stability of cementless acetabular cups depends on osseointegration, which requires primary stability of the implant. The aim of this study was to determine the influence of different surface treatments on the primary stability of press-fit acetabular cups. Mechanical lever-out tests were performed to quantify the stability in vitro. MATERIALS AND METHODS: A hemispherical press-fit cup design with a flattened pole was used and different surface modifications were applied: smooth, corundum-blasted, titanium plasma spray, rough titan plasma spray, and titanium plasma spray with a rim. The outer diameter of all cups was kept constant. Polyurethane foam was selected as the test material and cup insertion was performed with a maximal force of 6000 N. The excess length between the cup and the surface of the foam blocks was measured. The maximum lever-out force was measured and the lever-out torque was calculated. RESULTS: The excess length of cups with a smooth surface was significantly less (p<0.001) than for the other cups, with no significant differences among the other surface modifications. The lever-out torque for cups with a smooth surface was significantly less (p<0.001) than for the other cups, with no significant differences among the other surface modifications. CONCLUSION: Only the cup with a smooth surface showed significant differences for excess length and lever-out torque. The other surface modifications exhibited the same stability. As long as a rough surface is chosen, cup design seems to have a greater influence on stability than surface modification. Although the study did not mimic real in vivo conditions and the lever-out-torques cannot be transferred to clinical situations, initial stability before bony ingrowth occurred could be clearly analysed.     

A new technique to measure micromotion distribution around a cementless femoral stem

The interfacial micromotion is closely associated to the long-term success of cementless hip prostheses. Various techniques have been proposed to measure them, but only a few number of points over the stem surface can be measured simultaneously. In this paper, we propose a new technique based on micro-Computer Tomography (μCT) to measure locally the relative interfacial micromotions between the metallic stem and the surrounding femoral bone. Tantalum beads were stuck at the stem surface and spread at the endosteal surface. Relative micromotions between the stem and the endosteal bone surfaces were measured at different loading amplitudes. The estimated error was 10 μm and the maximal micromotion was 60 μm, in the loading direction, at 1400 N. This pilot study provided a local measurement of the micromotions in the 3 direction and at 8 locations on the stem surface simultaneously. This technique could be easily extended to higher loads and a much larger number of points, covering the entire stem surface and providing a quasi-continuous distribution of the 3D interfacial micromotions around the stem. The new measurement method would be very useful to compare the induced micromotions of different stem designs and to optimize the primary stability of cementless total hip arthroplasty.     

Predicting the subject-specific primary stability of cementless implants during pre-operative planning: preliminary validation of subject-specific finite-element models

Pre-operative planning help the surgeon in taking the proper clinical decision. The ultimate goal of this work is to develop numerical models that allow the surgeon to estimate the primary stability during the pre-operative planning session. The present study was aimed to validate finite-element (FE) models accounting for patient and prosthetic size and position as planned by the surgeon. For this purpose, the FE model of a cadaveric femur was generated starting from the CT scan and the anatomical position of a cementless stem derived by a skilled surgeon using a pre-operative CT-based planning simulation software. In-vitro experimental measurements were used as benchmark problem to validate the bone-implant relative micromotions predicted by the patient-specific FE model. A maximum torque in internal rotation of 11.4 Nm was applied to the proximal part of the hip stem. The error on the maximum predicted micromotion was 12% of the peak micromotion measured experimentally. The average error over the entire range of applied torques was only 7% of peak measurement. Hence, the present study confirms that it is possible to accurately predict the level of primary stability achieved for cementless stems using numerical models that account for patient specificity and surgical variability.     

Stair climbing is more critical than walking in pre-clinical assessment of primary stability in cementless THA in vitro

Pre-clinical testing of hip endoprostheses is a mandatory requirement before clinical release. Inadequate loading conditions may lead to lower elastic and plastic interface movements than those occurring post-operatively in vivo. This study investigated the influence of patient activity on the primary stability of cementless prostheses with a special emphasis on active simulation of muscle forces. A loading setup, based on validated musculo-skeletal analyses, was used to generate the hip contact force during walking and stair climbing by transmitting muscle forces through the femur. In addition, a loading configuration which only generated the hip contact force occurring during stair climbing at the prosthesis head was simulated. CLS prostheses were implanted in 18 composite femora and subjected to cyclical loading. The relative micro-movements at the bone-prosthesis interface were determined and appeared to be extremely sensitive to the specific patient activity. Compared to walking, stair climbing generated higher micro-movements, with pronounced axial and rotational components. Stair climbing with the femur loaded by the resultant hip contact force only exhibited a characteristic valgus tilt of the stem with significantly lower interface micro-movements than under active simulation of muscle forces. The analyses suggest that stair climbing induced the highest mechanical instability at the bone-prosthesis interface, a level which may compromise the necessary osseointegration process. Active simulation of muscle forces considerably affects the primary stability of cementless hip endoprostheses. Pre-clinical in vitro tests should therefore simulate stair climbing and include muscle activity in the assessment of initial implant stability, otherwise micro-movements may be underestimated and the primary stability overestimated.     

Shape optimization of a cementless hip stem for a minimum of interface stress and displacement

The primary stem stability is an essential factor for success of cementless hip stems. A correct choice of the stem geometry can improve the stem stability and, consequently, increase the life time of a hip implant. In this work, it is proposed a computational model for shape optimization of cementless hip stems. The optimization problem is formulated by the minimization of relative displacement and stress on bone/stem interface using a multi-criteria objective function. Also multiple loads are considered to incorporate several daily life activities. Design variables are parameters that characterize the geometry of selected cross sections, which are subject to geometric constraints to ensure a clinically admissible shape. The stem/bone set is considered a structure in equilibrium with contact conditions on interface. The contact formulation allows us to analyze different lengths of porous coating. The optimization problem is solved numerically by a steepest descent method. The interface stress and relative displacement are obtained solving the contact problem by the finite element method. Numerical examples are presented for a two-dimensional model of a hip stem, however, the formulation is general and can be applied to the three-dimensional case. The model gives indications about the relation between shape, porous coating and prosthesis stability.     

Quality of intertrochanteric cancellous bone as predictor of femoral stem RSA migration in cementless total hip arthroplasty

In cementless total hip arthroplasty, osteoporosis may jeopardize the achievement of immediate stability and lead to migration of anatomically shaped femoral stems. Poor quality of proximal cancellous bone per se may also affect the rate of osseointegration. In a selected group of female total hip arthroplasty patients (mean age 64 years) with unremarkable medical history, intertrochanteric cancellous bone biopsy was taken from the site of stem implantation. Local bone quality, determined by structural μCT imaging and destructive compression testing of the biopsy tissue, was used as the predictor of three-dimensional stem migration determined by radiostereometric analysis (RSA) up to 24 months. The patients exhibited major differences in mechanical properties of the intertrochanteric cancellous bone, which were closely related to the structural parameters calculated from μCT data. Unexpectedly, the major differences observed in the quality of trochanteric cancellous bone had only minor reflections in the RSA migration of the femoral stems. In statistical analysis, the μCT-based bone mineral density quartile (low, middle, high) was the only significant predictor for stem translation at 24 months (p=0.022) but only a small portion (R(2)=0.16) of the difference in translation could be explained by changes in bone mineral density quartile. None of the other parameters investigated predicted stem migration in translation or rotation. In conclusion, poor quality of intertrochanteric cancellous bone seems to contribute to the risk of implant migration less than expected. Probably also the importance of surgical preservation of intertrochanteric cancellous bone has been over-emphasized for osseointegration of cementless stem.     

Cementless stem fixation and primary stability under physiological-like loads in vitro.

Primary stability and in consequence osteointegration are commonly related to the stem anchorage but also to the complex musculoskeletal loading of the hip region. This study investigated the influence of metaphyseal and meta-diaphyseal anchorage on the primary stability of cementless stems under physiological-like loading in vitro. Metaphyseal and meta-diaphyseal anchoring stems (n=6 each) were implanted into composite femora. Musculoskeletal loads, validated by in vivo data (peak joint force 2348 N), were applied using a mechanical set-up. Interface movements were recorded by seven displacement transducers and primary stability was compared. Both stems exhibited similar movement patterns and principally moved distally with a retroversional twist. Although elastic movements were comparable, the metaphyseal stem exhibited higher plastic deformations than the meta-diaphyseal stem, particularly for the metaphyseal, medio-lateral and antero-posterior components. Under physiological-like loading, the metaphyseal stem allowed higher interface movements and tended to initially migrate faster than the meta-diaphyseal stem and then stabilized. Elastic movements were comparable and seemed to be less influenced by the anchoring concept than by the mechanical properties of the bone. The analyses emphasize the importance of metaphyseal bone in proximal anchorage and the necessity of an accurate canal preparation to prevent excessive initial migration.     

The stem state: mesenchymal plasticity as a paradigm

The mesenchyme is a remarkably plastic tissue in the embryo. Recent studies have led to the discovery of mesenchymal cells in the adult organism that can differentiate in vitro into unexpected directions, beyond the well-known ability of the mesenchyme to give rise to mesodermal derivatives. These studies highlighted the plastic nature of the mesenchyme, also beyond the embryonic developmental stage. This review discusses the possible functions of the mesenchyme in the adult and the reason for the maintenance of plasticity throughout mammalian life. The properties of the mesenchymal cells clearly exemplify the stem state concept; cells, whether early or late in the differentiation cascade, may assume a stem state that entails high plasticity.     

The pharmacist as a provider of primary care.

A survey was undertaken to document the primary health care role of the pharmacist in London, Ont. Of particular interest was the volume of primary contacts, the type of problem handled and the advice given by the pharmacist. The contribution of pharmacists in primary health care was found to be large, with neighbourhood pharmacies being the most active. Eighty percent of all problems were handled by recommending an over-the-counter drug. The pharmacist appears to be comfortable in this function, although a conflict may exist between his professional and merchant roles.     

Relative fitness of alternative male reproductive tactics in a mammal varies between years

1. In many species, males can use different behavioural tactics to achieve fertilization, so-called alternative reproductive tactics (ARTs). Few field studies have measured fitness consequences of ARTs under varying environmental conditions. 2. Here, we describe fitness consequences of three phenotypically plastic ARTs in the African striped mouse (Rhabdomys pumilio) and show that relative fitness of ARTs differs between years. Each year represents a different generation. 3. For the generation living under high population density, tactics differed in relative fitness in accordance with the theory of conditional strategies, with highly successful territorial breeding males having 10 times higher success than solitary roaming males and 102 times higher success than adult natally philopatric males. 4. For the generation living under intermediate population density, the territorial breeding and roaming tactics yielded similar fitness, which would be in agreement with the theory of mixed strategies. No philopatric males occurred. 5. For the generation living under low population density, roaming was the only tactic used and some roamers had very high fitness. 6. The main prediction of status-dependent selection for conditional strategies is a correlation between fitness and status, often measured as body mass, but we did not find this correlation within tactics when more than one tactic was expressed in the population. 7. Female distribution seems to have an effect on which reproductive tactics male chose: female defence polygyny when females are clumped (interference competition), but a searching tactic when females are dispersed (scramble competition). In contrast to predictions arising from theory on scramble competition, male body mass was important in determining fitness only in the year when females were dispersed, but not in other years. 8. Our results indicate that the differentiation between conditional and mixed strategies is not an absolute one. In many other species, environmental conditions might fluctuate temporally and spatially so that the normally suboptimal tactic yields similar fitness to the (usually) dominant tactic or that only a single tactic prevails. 9. We suggest the term single strategy, independent of current fitness consequences, for systems where tactics are not genetically determined, in contrast to genetically determined alternative strategies.     

Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence

Statistical analysis of 12 unstable and 32 stable proteins revealed that there are certain dipeptides, the occurrence of which is significantly different in the unstable proteins compared with those in the stable ones. Based on the impact of these dipeptides on the unstable proteins over the stable ones, a weight value of instability is assigned to each of the dipeptides. For a given protein the summation of these weight values normalized to the length of its sequence helps to distinguish between unstable and stable proteins. Results suggest that the in vivo instability of proteins is possibly determined by the order of certain amino acids in its sequence. An attempt is made to correlate metabolic stability of proteins with features of their primary sequence where weight values of instability for a protein of known sequence could thus be used as an index for predicting its stability characteristics.     

The evolution of population stability as a by-product of life-history evolution

Proposed mechanisms for the evolution of population stability include group selection through longterm persistence, individual selection acting directly on stability determining the demographic parameters, and the evolution of stability as a by-product of life-history evolution. None of these hypotheses currently has clear empirical support. Using two sets of Drosophila melanogaster populations, we provide experimental evidence of stability evolving as a correlated response to selection on traits not directly related to demography. Four populations (FEJs) were selected for faster development and early reproduction for 125 generations, and the other four (JBs) were ancestral controls. All FEJ and JB populations have been maintained on discrete generations at moderate density, thus eliminating differential selection on stability determining demographic parameters. We derived eight small populations from each FEJ and JB population, and subjected four small populations each to either stabilizing or destabilizing food regimes. Census data on these 64 small populations over 20 generations clearly showed that the FEJ populations have significantly less temporal fluctuations in their numbers in both food regimes compared to their controls. This greater stability of the FEJ populations is probably a by-product of the evolution of reduced fecundity and pre-adult survivorship, as a correlated response to selection for rapid development.     

The content of bone morphogenetic proteins in platelets varies greatly between different platelet donors

Platelet derivates and platelet rich plasma have been used to stimulate bone formation and wound healing because of the rich content of potent growth factors. However, not all reports have been conclusive since some have not been able to demonstrate a positive effect. We investigated the interindividual variation of bone morphogenetic proteins (BMPs) in platelets from healthy donors, and the pH-dependent effect on the release of BMPs in preparations of lysed platelets in buffer (LPB). Platelet concentrates from 31 healthy donors were prepared in pH 4.3 and pH 7.4 buffers and investigated with respect to BMP-2, -4, -6, and -7. BMP-2 and BMP-4 were significantly more common in acidic LPBs in comparison with neutral preparations. We also observed a considerable variation among platelet donors with respect to the release of BMPs at pH 4.3 and 7.4. In conclusion, a considerable variation was found among platelet donors, which may be of importance considering the ambiguous results previously reported on osteoblast proliferation and differentiation.     

Experimental method for the in vitro testing of the initial stability of cementless hip prostheses

Micromotions at the interface between bone and prosthesis are believed to induce bone resorption and ultimately lead to loosening of the implant. Thus the initial stability achieved by a hip prosthesis is an important factor for the long-term function of the implant. Knowing the biological consequences of the mechanical conditions, it appears to be mandatory to measure the extent of these three-dimensional movements. An in vitro dynamic method for measurement of the micromotion of the femoral component of hip prostheses has been developed. Tests in cemented prostheses have confirmed that the use of cement reduces sinkage and rotation manyfold and have yielded reference values for stability. Comparison with two types of cementless prostheses has shown that certain cementless implants may achieve stability comparable to cemented ones in some load directions.