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Biomedical subjects

R A Brand

Publications and source records attributed to R A Brand.

At least 19 recordsLinked to original sources

Cartilage anlagen adapt in response to static deformation.

Connective tissue adaptation, including the development of cartilaginous anlagen into bones, is widely believed to be related to dynamic, intermittent load and stress histories. Static stresses, on the other hand, are generally believed deleterious in tissue adaptation. Using serial MRI in a natural human experiment (manipulation and corrective casting of infant clubfoot), we have observed casting produces two effects: (1) the well recognized change in relative positions of the hindfoot anlagen; (2) a newly recognized immediate shape change in the anlagen. These changes seemingly enhance the rate of growth of the anlagen and of the ossific nucleus. The shape change or deformation in the anlagen would occur as a result of alterations in the magnitudes and directions of loading from soft tissue attachments and muscle activity and would necessarily be associated with changes in the stress states within the anlagen and, when present, the ossific nuclei. Given the known role of load and stress history in tissue adaptation, we presume the reduced stress histories influence the enhanced growth rates. These observations contradict some current theories of tissue adaptation since static, rather than dynamic stresses play a crucial role in accelerating the growth and development of anlagen in the infant clubfoot.

Biomechanical Phenomena↗

Modeling deformation-induced fluid flow in cortical bone's canalicular-lacunar system.

To explore the potential role that load-induced fluid flow plays as a mechano-transduction mechanism in bone adaptation, a lacunar-canalicular scale bone poroelasticity model is developed and implemented. The model uses micromechanics to homogenize the pericanalicular bone matrix, a system of straight circular cylinders in the bone matrix through which bone fluids can flow, as a locally anisotropic poroelastic medium. In this work, a simplified two-dimensional model of a periodic array of lacunae and their surrounding systems of canaliculi is used to quantify local fluid flow characteristics in the vicinity of a single lacuna. When the cortical bone model is loaded, microscale stress, and strain concentrations occur in the vicinity of individual lacunae and give rise to microscale spatial variations in the pore fluid pressure field. Furthermore, loading of the bone matrix containing canaliculi generates fluid pressures in the contained fluids. Consequently, loading of cortical bone induces fluid flow in the canaliculi and exchange of fluid between canaliculi and lacunae. For realistic bone morphology parameters, and a range of loading frequencies, fluid pressures and fluid-solid drag forces in the canalicular bone are computed and the associated energy dissipation in the models compared to that measured in physical in vitro experiments on human cortical bone. The proposed model indicates that deformation-induced fluid pressures in the lacunar-canalicular system have relaxation times on the order of milliseconds as opposed to the much shorter times (hundredths of milliseconds) associated with deformation-induced pressures in the Haversian system.

Animals↗

Micromechanically based poroelastic modeling of fluid flow in Haversian bone.

To explore the hypothesis that load-induced fluid flow in bone is a mechano-transduction mechanism in bone adaptation, unit cell micro-mechanical techniques are used to relate the microstructure of Haversian cortical bone to its effective poroelastic properties. Computational poroelastic models are then applied to compute in vitro Haversian fluid flows in a prismatic specimen of cortical bone during harmonic bending excitations over the frequency range of 10(0) to 10(6) Hz. At each frequency considered, the steady state harmonic response of the poroelastic bone specimen is computed using complex frequency-domain finite element analysis. At the higher frequencies considered, the breakdown of Poisueille flow in Haversian canals is modeled by introduction of a complex fluid viscosity. Peak bone fluid pressures are found to increase linearly with loading frequency in proportion to peak bone stress up to frequencies of approximately 10 kHz. Haversian fluid shear stresses are found to increase linearly with excitation frequency and loading magnitude up until the breakdown of Poisueille flow. Tan delta values associated with the energy dissipated by load-induced fluid flow are also compared with values measured experimentally in a concurrent broadband spectral analysis of bone. The computational models indicate that fluid shear stresses and fluid pressures in the Haversian system could, under physiologically realistic loading, easily reach the level of a few Pascals, which have been shown in other works to elicit cell responses in vitro.

Adaptation, Physiological↗

Primary adult human bone cells do not respond to tissue (continuum) level strains.

Bone adapts to its mechanical environment, and, since the late 1800s, investigators have presumed that this adaptation relates to strain magnitude. Indeed, overwhelming evidence supports the view that either strain or some strain-related quantity stimulates bone adaptation or remodeling. Virtually all investigators, implicitly or explicitly, assume that the level of strain magnitude responsible for bone adaptation is that measured by strain gauges in vivo (i.e., 100-2500 microstrain) and that bone cells are directly deformed by strained matrix. We present evidence that bone cell deformation in this range does not cause bone adaptation. First, bone cells in vitro typically do not respond to average (continuum) levels of strain magnitude. Second, bone cells in vitro do respond to fluid flow-induced shear stresses in these ostensible physiological ranges. Third, in vivo strain magnitudes presumed to stimulate remodeling reflect only averages, and not local peaks, which are 2-15 times higher. Thus, we hypothesize that sensing cells do not respond to levels of strain presumed to be physiological.

Adaptation, Physiological↗

Cell alignment is induced by cyclic changes in cell length: studies of cells grown in cyclically stretched substrates.

Many types of cells, when grown on the surface of a cyclically stretched substrate, align away from the stretch direction. Although cell alignment has been described as an avoidance response to stretch, the specific deformation signal that causes a cell population to become aligned has not been identified. Planar surface deformation is characterized by three strains: two normal strains describe the length changes of two initially perpendicular lines and one shear strain describes the change in the angle between the two lines. The present study was designed to determine which, if any, of the three strains was the signal for cell alignment. Human fibroblasts and osteoblasts were grown in deformable, rectangular, silicone culture dishes coated with ProNectin, a biosynthetic polymer containing the RGD ligand of fibronectin. 24 h after plating the cells, the dishes were cyclically stretched at 1 Hz to peak dish stretches of 0% (control), 4%, 8%, and 12%. After 24 h of stretching, the cells were fixed, stained, and their orientations measured. The cell orientation distribution was determined by calculating the percent of cells whose orientation was within each of eighteen 5 degrees angular intervals. We found that the alignment response was primarily driven by the substrate strain which tended to lengthen the cell (axial strain). We also found that for each cell type there was an axial strain limit above which few cells were found. The axial strain limit for fibroblasts, 4.2 +/- 0.4%, (mean +/- 95% confidence), was lower than for osteoblasts, 6.4 +/- 0.6%. We suggest that the fibroblasts are more responsive to stretch because of their more highly developed actin cytoskeleton.

Adolescent↗

Venous thromboembolic disease management patterns in total hip arthroplasty and total knee arthroplasty patients: a survey of the AAHKS membership.

The American Association of Hip and Knee Surgeons (AAHKS) distributed a survey to its members exploring practice patterns implemented to prevent venous thromboembolic disease (VTED) in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Of 720 (33%) members, 236 responded. Prophylaxis was prescribed for 100% of patients during the course of hospitalization for THA and TKA. Warfarin was the commonest pharmacologic treatment used for THA (66%) and TKA (59%) patients. Low-molecular-weight heparin was used in 16% of THA patients and 18% of TKA patients. The most commonly employed mechanical modality was pneumatic devices in THA (51%) and TKA (50%). Universal acceptance of the need for prophylaxis administration for patients undergoing THA and TKA is shown. The method and duration remain highly variable; although the survey illustrates such variation, it suggests there is no one best method of prophylaxis.

Anticoagulants↗

A broadband viscoelastic spectroscopic study of bovine bone: implications for fluid flow.

To explore the hypothesis that mechanical excitation-induced fluid flow and/or fluid pressure are potential mechanical transduction mechanisms in bone adaptation, a complementary experimental and analytical modeling effort has been undertaken. Experimentally, viscoelastic tan delta properties of saturated cortical bovine bone were measured in both torsion and bending, and significant tan delta values in the 10(0)-10(5) Hz range were observed, although the nature of the damping is not consistent with a fluid pressure hypothesis. Analytically, micromechanically based poroelasticity models were exercised to quantify energy dissipation associated with load-induced fluid flow in large scale channels. The modeling results indicate that significant damping due to fluid flow occurs only above 1 MHz frequencies. Together, the experimental and analytical results indicate that at excitation frequencies presumed to be physiological (1-100 Hz), mechanical loading of bone generates extremely small pore fluid pressures, making the hypothesized fluid-pressure transduction mechanism upon osteocytes untenable.

Animals↗

Primary human bone cultures from older patients do not respond at continuum levels of in vivo strain magnitudes.

Osteoporosis is characterized by excessive loss of bone mass, while exercise is believed to maintain or enhance bone mass. Since exercise marginally affects osteoporosis, we wondered whether bone cells from osteoporotic patients would fail to respond to strain. Primary human bone-like cultures were obtained from females over age 60 with hip arthroplasty procedures performed for either osteoporotic fracture (n = 8) or non-osteoporotic osteoarthrosis (n = 5). Cultures (96,000 cell/cm2) were strained in rectangular optically clear silastic wells. Three periods of uniaxial substratum strain (1000 micro-strain, 1 Hz, 10,000 cycles, sine wave) were provided every 24 h using a four-point bending, computer-controlled device. Results at a frequency of 1 Hz were compared to cultures exposed to 20 Hz with bone cells derived from one osteoarthritic subject. Alterations in protein level expression of bone-related proteins were determined using a semi-quantitative confocal approach along with enzyme (alkaline phosphatase) activity and enzyme mRNA copy number using cRNA RT-PCR. Strain did not alter levels of bone-related protein levels, enzyme activity, or steady state copy number per cell in response to strain in either group. Strained cultures from osteoporotic patients exhibited little variation from unstrained controls, while individual cultures from osteoarthritic patients exhibited increases in one protein or the other. The results suggest that bone cells from older individuals may not be responsive to continuum levels of strain anticipated with vigorous activity.

Aged↗

Cell mechanics.

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Biomechanical Phenomena↗

Mathematical modelling of stress in the hip during gait.

A mathematical model is developed for calculating the contact stress distribution in the hip for a known resultant hip force and characteristic geometrical parameters. Using a relatively simple single nonlinear algebraic equation, the model can be readily applied in clinical practice to estimate the stress distribution in the most frequent body positions of everyday activities. This is demonstrated by analyzing the data on the resultant hip force obtained from laboratory observations where a stance period of gait is considered.

Acetabulum↗

Toward an understanding of implant occlusion and strain adaptive bone modeling and remodeling.

STATEMENT OF PROBLEM: Dental implant failure rates for osseointegration are greater in the highly atro-phic maxilla. Presuming higher failure rates relate to strain-driven adaptation, an enhanced understanding of formative bone response to loading (modeling) and maintenance of an integrated state (remodeling) should improve treatment. PURPOSE: To understand the role of occlusal loading on long-term osseointegration in areas of compromised cancellous bone, a review of the salient features of adaptive bone modeling and remodeling is presented with an emphasis on cancellous bone responses. CONCLUSIONS: The ability for dental implants to maintain a long-term stable interface in the maxilla lies in the ability of trabecular bone to maintain adequate local material (strength) and architectural (connectivity) properties. In this discussion, an emphasis has been placed on understanding how trabecular bone can respond to the mastication-induced loading environment on an implant.

Adaptation, Physiological↗

Testing the daily stress stimulus theory of bone adaptation with natural and experimentally controlled strain histories.

Theories of bone adaptation generally consider that a departure in some feature of the normal homeostatic mechanical stimulus governs mechanical adaptation. Specifically, the 'daily stress stimulus' theory commonly used in computational models of bone adaptation suggests that the mechanical stimulus arises from a synthesis of the peak magnitudes from each loading event during a day. In this study, the homeostatic daily strain history of the adult turkey ulna was established by categorizing and counting the natural wing activities of adult male turkeys over a full 24h period. Strain signals were recorded in vivo for each activity type at three mid-diaphysis sites using stacked rosette strain gages. Following surgical isolation and transverse metaphyseal pinning of the ulnae, additional strain signals were recorded during controlled axial and torsional loading regimens associated with documented maintenance, loss, or addition of bone mass. When the present data were incorporated into the daily stress stimulus formulation, the theory did not consistently discriminate maintenance versus formation regimens, i.e., some maintenance regimens were associated with a substantially higher daily stimulus than some regimens causing bone formation.

Adaptation, Physiological↗