Is trabecular bone permeability governed by molecular ordering-induced fluid viscosity gain? Arguments from re-evaluation of experimental data in the framework of homogenization theory.

It is generally agreed on that trabecular bone permeability, a physiologically important quantity, is governed by the material׳s (vascular or intertrabecular) porosity as well as by the viscosity of the pore-filling fluids. Still, there is less agreement on how these two key factors govern bone permeability. In order to shed more light onto this somewhat open issue, we here develop a random homogenization scheme for upscaling Poiseuille flow in the vascular porosity, up to Darcy-type permeability of the overall porous medium "trabecular bone". The underlying representative volume element of the macroscopic bone material contains two types of phases: a spherical, impermeable extracellular bone matrix phase interacts with interpenetrating cylindrical pore channel phases that are oriented in all different space directions. This type of interaction is modeled by means of a self-consistent homogenization scheme. While the permeability of the bone matrix equals to zero, the permeability of the pore phase is found through expressing the classical Hagen-Poiseuille law for laminar flow in the format of a "micro-Darcy law". The upscaling scheme contains pore size and porosity as geometrical input variables; however, they can be related to each other, based on well-known relations between porosity and specific bone surface. As two key results, validated through comprehensive experimental data, it appears (i) that the famous Kozeny-Carman constant (which relates bone permeability to the cube of the porosity, the square of the specific surface, as well as to the bone fluid viscosity) needs to be replaced by an again porosity-dependent rational function, and (ii) that the overall bone permeability is strongly affected by the pore fluid viscosity, which, in case of polarized fluids, is strongly increased due to the presence of electrically charged pore walls.

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.

Mathematical modeling of postmenopausal osteoporosis and its treatment by the anti-catabolic drug denosumab.

Denosumab, a fully human monoclonal antibody, has been approved for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab rests on its ability to inhibit osteoclast differentiation. Here, we present a computational approach on the basis of coupling a pharmacokinetics model of denosumab with a pharmacodynamics model for quantifying the effect of denosumab on bone remodeling. The pharmacodynamics model comprises an integrated systems biology-continuum micromechanics approach, including a bone cell population model, considering the governing biochemical factors of bone remodeling (including the action of denosumab), and a multiscale micromechanics-based bone mechanics model, for implementing the mechanobiology of bone remodeling in our model. Numerical studies of postmenopausal osteoporosis show that denosumab suppresses osteoclast differentiation, thus strongly curtailing bone resorption. Simulation results also suggest that denosumab may trigger a short-term bone volume gain, which is, however, followed by constant or decreasing bone volume. This evolution is accompanied by a dramatic decrease of the bone turnover rate by more than one order of magnitude. The latter proposes dominant occurrence of secondary mineralization (which is not anymore impeded through cellular activity), leading to higher mineral concentration per bone volume. This explains the overall higher bone mineral density observed in denosumab-related clinical studies.

Characterization of the deformation behavior of intermediate porosity interconnected Ti foams using micro-computed tomography and direct finite element modeling.

Under load-bearing conditions metal-based foam scaffolds are currently the preferred choice as bone/cartilage implants. In this study X-ray micro-computed tomography was used to discretize the three-dimensional structure of a commercial titanium foam used in spinal fusion devices. Direct finite element modeling, continuum micromechanics and analytical models of the foam were employed to characterize the elasto-plastic deformation behavior. These results were validated against experimental measurements, including ultrasound and monotonic and interrupted compression testing. Interrupted compression tests demonstrated localized collapse of pores unfavorably oriented with respect to the loading direction at many isolated locations, unlike the Ashby model, in which pores collapse row by row. A principal component analysis technique was developed to quantify the pore anisotropy which was then related to the yield stress anisotropy, indicating which isolated pores will collapse first. The Gibson-Ashby model was extended to incorporate this anisotropy by considering an orthorhombic, rather than a tetragonal, unit cell. It is worth noting that the natural bone is highly anisotropic and there is a need to develop and characterize anisotropic implants that mimic bone characteristics.

Emergency ambulance transport induces stress in patients with acute coronary syndrome.

BACKGROUND: Trials with healthy volunteers have shown that emergency ambulance transportation induces stress, which becomes evident by an increase in heart rate, blood pressure and plasma levels of stress hormones such as adrenaline, noradrenaline, cortisol and prolactin. A study was undertaken to test the hypothesis that emergency ambulance transportation may also lead to stress in patients with acute coronary syndrome. METHODS: Venous plasma levels of epinephrine, norepinephrine and lactate as well as visual analogue scale (VAS) scores for pain and anxiety were measured in 32 patients with defined clinical signs of acute coronary syndrome before and after transportation. Heart rate, blood pressure and transcutaneous oxygen saturation levels were recorded every 3 min. RESULTS: Mean (SD) plasma levels of epinephrine and norepinephrine increased significantly (p<0.01) during transportation (159.29 (55.34) ng/l and 632.53 (156.32) ng/l before transportation vs 211.03 (70.12) ng/l and 782.93 (173.95) ng/l after transportation), while lactate levels, heart rate and mean blood pressure remained almost stable. There was no significant change in mean (SD) VAS scores for pain and anxiety (3.79 (3.70) and 2.89 (3.01) vs 2.13 (3.30) and 1.57 (2.78)). CONCLUSION: Emergency ambulance transportation induces a rise in plasma catecholamine levels and therefore stress in patients with acute coronary syndrome, but does not result in cardiac shock as lactate levels and haemodynamic parameters remain normal.

Finite element simulation of the human mandible: the role of (natural) teeth.

INTRODUCTION: Individual bone quality depends on genetic, biological, and mechanical influencing factors, where the latter is accessible via Finite Element Simulation. This work is part of an interdisciplinary research project with the purpose of stepwise refinement towards anatomical reality. This approach opened the door for many interrelated applications such as atrophy of the jaw bone, periodontology, implantology, or TMJ disorders. This lecture is dedicated to the influence of dental anatomy on mandibular biomechanics. MATERIALS AND METHODS: In general, biomechanical simulation requires reconstruction of the individual anatomy, implementation of the inhomogeneous and anisotropic material law of bone, and realization of the load case due to tooth, muscle and joint forces. The simulation chain ranges from image processing of CT data up to specifically adapted post-processing of the simulation results. In spite of ongoing research, there is still a fundamental difference of dental implants compared to natural teeth: the periodontal ligament (PDL) present at the interface between teeth and mandibular corpus. Due to its thickness of about 0.2 mm, the PDL was introduced to the simulation model by a special semiautomatic procedure. RESULTS: Simulations "with and without PDL" proved remarkable force absorption due to the PDL, as well as qualitative changes of the stress/strain profiles of the alveolar ridge. Concerning the simulation without PDL, the observed high compressive strains at the adjacent bone were in agreement with regions of frequent implant failure. CONCLUSION: The PDL is essential for the structural behavior of the human mandible. Based on the mechanical adaptation of bone, the comparison of the simulation with and without PDL provided special insight to the changes due to dental implants, in particular implant loss and bone resorption. Finally, the simulation will serve as a virtual platform for further evaluation (a) of implant design (b) of implant placement.

Mandibular finite element simulation as a tool for trauma surgery.

PURPOSE: Despite remarkable progress within the last decade, the treatment of mandibular fractures is still a highly discussed topic in oral and cranio-maxillofacial surgery. The possible traumatologic scenarios are characterized by high variability. A current project is focused on "resimulation" of traumatologic cases given by clinical radiographs by means of finite element method. METHODS: The applied finite element model of the mandible is very refined, providing detailed dental anatomy especially of the periodontal ligament. The mandible was modelled as inhomogeneous and anisotropic. The temporomandibular joints were realized as simplified joint capsules, wherein the mandibular condyles are freely mobile with certain limitations. The user has the choice of 5 regions on the mandibular surface where the virtual injury can be inflicted. Power and direction of the impact force vector can be set at will. The masticatoy system including the digastrics and the mylohyoid muscles can be activated. RESULTS: The situations given by radiographs could be "reproduced" by a simulation scenario characterized by high compressive strain at the location of fractures. If masticatory muscles were activated and teeth clenched, the stress/strain profiles were qualitatively changed. DISCUSSION: The approach may be of benefit for optimized behavior with regard to certain sports or vocations. For forensic analysis, the method will contribute by elimination of scenarios not matching the given fracture locations. Nevertheless, the immediate purpose of our approach is a better understanding of the injured organ's condition. Fractures of bone as an adaptive biological tissue differ fundamentally from mechanical failure in engineering. Many of our trauma simulations showed elevated stress/strain around the fracture, leading to the suggestion of weakened bone there. This finding was confirmed by surgical observation.

Consideration of anisotropic elasticity minimizes volumetric rather than shear deformation in human mandible.

This article is focused on the role of anisotropic elasticity in the simulation of the load distribution in a human mandible, due to a lateral bite on the leftmost premolar. Based on experimental evidence, orthotropy of the elastic properties of the bone tissue has been adopted. The trajectories of anisotropic elasticity are reconstructed from (i) the organ's geometry and (ii) from coherent structures which can be recognized from the spatial distribution of the grey values coming from computer tomography (CT). A sensitivity analysis comprising various three-dimensional (3D) finite element (FE) simulations reveals the relevance of elastic anisotropy for the load carrying behavior of a human mandible: comparison of the load distributions in isotropic and anisotropic simulations indicates that anisotropy seems to "spare" the mandible from loading. Moreover, a maximum degree of anisotropy leads to kind of load minimization of the mandible, expressed by a minimum of different norms of local volumetric strain, evaluated throughout the organ. The observed optimization with respect to volumetric rather than shear strain seems to confirm the frequently emphazised role of volumetric-strain-induced fluid flow for the stimulation of cellular activity.

Average hydroxyapatite concentration is uniform in the extracollagenous ultrastructure of mineralized tissues: evidence at the 1-10-microm scale.

At the ultrastructural observation scale of fully mineralized tissues (l=1-10 mum), transmission electron micrographs (TEM) reveal that hydroxyapatite (HA) is situated both within the fibrils and extrafibrillarly, and that the majority of HA lies outside the fibrils. The extrafibrillar amount of HA varies from tissue to tissue. By means of mathematical modeling, we here provide strong indications that there exists a physical quantity that is the same inside and outside the fibrils, for all different fully mineralized tissues. This quantity is the average mineral concentration in the non-collagenous space. This space is the sum of the extrafibrillar volume and of the volume of the fibrils that is not occupied by collagen molecules. Two independent sets of experimental observations covering a large range of tissue mass densities establish the relevance of our proposition: (i) mass density measurements and diffraction spacing measurements, re-analyzed through a dimensionally consistent packing model; (ii) optical density measurements of TEMs. The aforementioned average uniform HA-concentration in the extracollagenous space of the ultrastructure may emphasize the putative role played by a number of non-collagenous organic molecules in providing the chemical boundary conditions for mineralization of HA in the extracollagenous space. The probable existence of an average uniform extracollagenous HA concentration has far-reaching consequences for the mechanical behavior of mineralized tissues.

[The efficacy of oral betamimetics using an oxytocin-stimulated puerperal model (author's transl)]. / Uber die Wirksamkeit oral applizierter Betamimetika am oxytocinstimulierten puerperalen Modell.

Puerperal uteri were stimulated by oxytocin, the uterine motility was recorded by transcervical catheter techniques, maternal pulse and blood-pressure were recorded continuously or intermittently. Oral tocolytics as Gynipral (Hexoprenaline), Partusisten (Fenoterol), Spiropent (Clenbuterol) and Prepar (Ritodrine) were administered orally in single or double dose. The inhibitory effect of these drugs were recorded, evaluated from the records and calculated statistically concerning their significant differences. It could be demonstrated that only Hexoprenaline in a three time higher dose than used usually and Partusisten in a dose of 10 and 20 mg were able to reduce uterine motility for more than 50%. All other substances definitely had an inhibitory effect on the puerperal uterus, but inhibition was not stronger than 30%. Cardiovascular side-effects were discussed. The question, if oral given betamimetics are effective in the treatment of threatening premature labour could not be answered definitively, but there are doubts according this study concerning the dose and the repetition of it for this purpose.