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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

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.

Explore the source record for details and available documents.

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↗

Pelvic muscle and acetabular contact forces during gait.

Locations, magnitudes, and directions of pelvic muscle and acetabular contact forces are important to model the effects of abnormal conditions (e.g., deformity, surgery) of the hip accurately. Such data have not been reported previously. We computed the three-dimensional locations of all pelvic muscle and acetabular contact forces during level gait. The approach first required computation of the intersegmental joint resultant forces and moments using limb displacement history, foot-floor forces, and estimated limb inertial properties from one subject. The intersegmental resultant moments were then distributed to the muscles using a 47-element muscle model and a non-linear optimization scheme. Muscle forces were vectorally subtracted from the intersegmental resultants to compute the acetabular contact forces. While the peak joint force magnitudes are similar to those reported previously for the femur, the directions of pelvic contact forces and muscle forces varied considerably over the gait cycle. These variations in contact force directions and three-dimensional forces could be as important as the contact force magnitudes in performing experimental or theoretical studies of loads and stresses in the periacetabular region.

Acetabulum↗

Sensory innervation of the cat knee articular capsule and cruciate ligament visualised using anterogradely transported wheat germ agglutinin-horseradish peroxidase.

Wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) was injected into the dorsal root ganglia (L5-S1) of the cat and used as an anterograde tracer substance for intra-axonal labelling of peripheral nerve endings in joint capsule and cranial (anterior) cruciate ligament (CCL). We believed that the high specificity of WGA-HRP for neural tissue along with the high visibility of its reaction product could help resolve controversies concerning the sensory innervation of the cruciate ligaments. Substantial amounts of WGA-HRP were transported in tibial nerve axons to the level of the knee. However, using standard HRP histochemistry we found that the capsular tissue and ligament synovia disintegrated during the incubation reaction. This problem was avoided by air drying the tissue slices on glass slides prior to reaction. Abundant labelling occurred in the posterior capsule with dense filling of axons and terminal endings. Sensory endings displayed features consistent with Ruffini endings and pacinian corpuscles. Sensory endings were located throughout the CCL in its sagittal plane, in the subsynovial layers and between collagen fascicles. In each CCL we observed 5-17 ovoid and elongated endings with dense terminal arborisations. These endings were between 100 and 150 microns long, were encapsulated, and gave rise to 1 or 2 axons. Large (up to 1.5 mm in maximum extent) elongated regions of dense, inhomogeneous labelling were found in the body of several CCLs. These resembled Golgi tendon-like endings, with the exception of their large size. We conclude that anterograde transport of HRP to the knee is a useful technique for labelling mechanoreceptors and axons in knee tissue. However, recently developed immunohistochemical analysis of peripheral tissue using protein gene product 9.5 appears to be the method of choice and should be employed for further study of human and animal cruciate ligament innervation.

Animals↗

Popliteus function in ACL-deficient patients.

Anterior cruciate ligament (ACL) injuries commonly result in anterolateral rotary instability and a 'pivot shift' phenomenon. Since popliteus muscle stimulation causes a pivot shift, some postulate the popliteus muscle plays a role in causing pivot shifts. To see if patients with pivot shifts exhibited excessive popliteus muscle activity, we studied fine-wire EMGs of the popliteus in 16 normal subjects and 10 ACL-deficient subjects. Subjects performed six activities (level walking and jogging, ascending walking and jogging, and descending walking and jogging). Except for minor timing differences in ascending treadmill and ascending jogging, the signals were similar for injured and uninjured limbs; similar variance ratios suggested similar pattern variability. Thus, we observed only minor popliteus EMG signal differences in this group of patients. We conclude that the popliteus muscle does not actively contribute to instability in the studied activities.

Anterior Cruciate Ligament Injuries↗

A cell strain system for small homogeneous strain applications.

A cell culture system has been developed that enables application of well characterized, homogeneously distributed cyclic strains to monolayer cell cultures. Optically clear silicone culture dishes atop Plexiglas base plates are deformed by four-point bending of flexible silicone culture wells driven in user specified strain cycle patterns using computer controlled electromagnetic linear actuators. Cyclic mechano-transduction can be induced in amplitudes of 0 to 3000 mustrain, in frequencies of 0 to 30 Hz and in any specified strain cycle pattern. The cell culture system, which contains six simultaneously driven culture wells, has been mechanically characterized by holographic interferometry, laser displacement sensor recordings of the dish surfaces, strain gauge monitoring of the base plates, and finite element modeling of the dishes on the base plates. The standard deviation of the strain amplitudes among the six simultaneously stimulated culture wells is less than 5%. The cell culture system allows accurate generation of small magnitudes of well characterized, homogeneous strain, easy handling of the culture wells, flexible setting of cyclic strain pattern parameters, simultaneous stimulation of 6 culture wells, and light microscopic observation of the cell cultures.

Animals↗