Mechanics & Materials
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Osteocyte bone cell deformation: Advanced displacement and strain mapping techniques are used to quantify the deformation of individual osteocyte bone cells subjected to fluid flow and substrate stretching.
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SwRI custom-designed micromechanical testing device is designed to operate within upright or inverted optical and laser scanning confocal microscopes. Load is applied to the specimen in the center of the device using two opposing digital stepper motors. The device can be operated using the motors synchronously, thus applying equal and opposite loads to the specimen to keep it centered under the microscope objective.
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Atomic force microscopy image of a lightly etched polished surface of cortical bone reveals the collagen organization in and around an osteocyte lacuna.
The bone mechanics research program is focused on understanding the relationship between bone mechanical and biological functions, advanced characterization of bone tissue material and mechanical properties, and developing and applying advanced engineering methods to predict an individual's risk of bone fracture.
Micromechanics of Osteocyte Deformation
A major goal of this program is to determine osteocyte function in response to mechanical loading. To accomplish this goal it will be necessary to relate osteocyte deformation and/or strain in bone tissue to the expression and function of different molecules expressed by osteocytes in response to mechanical loading.
Well-defined in vitro, ex vivo and in vivo mechanical loading systems are of paramount importance in understanding the role that mechanical strain plays in osteocyte biology. This project will provide support to conduct in vivo and in vitro loading of bones and bone cells, as well as the capability to image cells in vitro and ex vivo during application of mechanical stimuli enabling the quantification of individual cell deformations. In addition, important questions regarding cell deformation in response to mechanical stimulation will be investigated. Understanding the physical deformation of osteocytes due to different mechanical stimulation will provide needed insight into differences observed in cell response.
Data from our laboratory suggest that the hypothesis that bone cells do not respond to bone matrix strain may be incorrect. We have shown that local peri-lacunar bone matrix strain can be up to 15,000 microstrain, an order of magnitude greater than in vivo bone surface strains measured using a strain gage, and, on average the local tissue strain is 4,000 to 7,000 microstrain when macroscopic strains of 2,000 microstrain are applied to bone. We have shown that in vitro osteocyte cell deformation due to this level of shear stress can be between approximately 5,000 and 50,000 microstrain with a concomitant biological response measured as an increase in PGE2 production.
The research goals of this project are to quantify osteocyte deformation in vitro resulting from both fluid flow generated shear stress and substrate stretching. Furthermore, to extend our current research findings, we will measure osteocyte deformation ex vivo in mice long bones due to globally applied structural bending loads. We will also begin to characterize the osteocyte microenvironment, which is integral in transmitting global structural loads and deformations to the osteocyte, by atomic force microscopy, nanoindentation, and direct Raman imaging.
Non-Invasive Characterization of Bone Microdamage
Humans experience an age-related increase in the incidence of skeletal fractures and this increase may be due to a variety of factors including a decrease in bone mineral density, impaired balance and reflexes, changes in the shape and size of bones, changes in bone porosity and microarchitecture, alterations in bone mineral and organic constituents, and microdamage accumulation. The latter three factors, often referred to as "bone quality," are increasingly recognized as important determinants of fracture risk, especially for osteoporotic patients. The current National Institutes of Health Consensus Statement describes bone strength as an integration of two main features: bone density and bone quality. Bone mineral density (BMD) measurements are widely used for determining bone strength, especially in women, and can account for 70% of bone strength. Nonetheless, a more accurate overall measurement of bone strength is still needed. For example, recent studies involving the use of antiresorptive drugs have shown that increases in BMD due to antiresorptive therapy only account for 4% of the reduction in fracture risk; the remaining 96% is left unexplained.
Quantification of measures of bone quality such as microdamage accumulation and other microstructural characteristics may lead to a more accurate measure of bone strength and therefore fracture risk. It has been shown that age related increases in bone porosity without significant changes in bone mineral density result in a decrease in bone strength. Bone fracture toughness is also significantly correlated to changes in porosity, microarchitecture, osteonal morphology, collagen integrity, and microdamage, all of which are measures of bone quality. Furthermore, microdamage accumulation increases significantly with age, more dramatically in women than in men, and may be a significant contributor to osteoporotic bone fragility.
Unfortunately, current technology does not allow the nondestructive and non-invasive detection of bone microdamage or other measures of bone quality including microporosity; currently accepted techniques require serial sectioning and microscopic examination of bone specimens. On the other hand, nuclear magnetic resonance (NMR) proton spin-spin (T2) or spin-lattice (T1) relaxation time measurements and analytical processing techniques have been used to determine microstructural characteristics of various types of fluid-filled porous materials. This method has been used to quantify the porosity, pore size distribution, and permeability in oil reservoirs where the pores in the rock structure range in size from sub micron to sub millimeter. Since bone is also a fluid filled porous material, we propose to develop a rapid, nondestructive and non-invasive technique based on low field pulsed NMR to detect and quantify bone microdamage and porosity and relate these measurements to measures of bone mechanical properties. This new information may then be used in combination with or replace existing methods (BMD measurements) to more accurately assess fracture risk.
We have developed a nondestructive technique to assess bone quality by quantifying microdamage, porosity, and pore size distribution in cortical bone. Non-invasive NMR relaxation time measurements are used to characterize cortical bone microdamage, porosity, and pore size distribution (measures of bone quality) and can subsequently augment or replace traditional bone mineral measurements to predict cortical bone mechanical properties. Specifically, we have shown that cortical bone microdamage results in an alteration of the NMR spin-spin (T2) relaxation time signal due to the creation of new internal surfaces (microfractures) in the bone matrix compared to undamaged bone. This signal is further processed to produce a T2 relaxation distribution spectrum related to both the size distribution of microdamage and pore size distribution in cortical bone. We have also shown that the NMR spin-spin relaxation time (T2) spectrum derived parameters can be used as descriptions of bone quality (e.g. matrix microdamage and porosity size distributions) and, alone or in combination with current techniques (bone mineral density measurements), more accurately predict bone mechanical properties.
Determining the Probability of Vertebral Failure
This project aims to develop and investigate a novel means of determining the risk of fracture of skeletal systems. The problem of increased risk of fracture as a result of bone mass loss due to aging or disease is a major clinical concern, and has been the focus of a substantial research effort. Although some correlative relationships have been established between fracture risk and various imaging and biochemical data, these methods remain nonspecific and have low sensitivity for predicting fracture risk. Clearly, an accurate means of predicting risk of fracture for an individual subject would have tremendous clinical benefit.
Experimental vs. predicted cumulative distribution function (CDF) of the maximum stress attained during a probabilistically simulated tensile test of cortical bone.
We are combining several analysis techniques that have not been used together before to produce a rigorously verified and validated, physics based approach to quantify the probability or risk of bone fracture. Namely, probabilistic finite element methods will provide a framework for accounting for uncertainty and randomness inherently involved in the mechanics of skeletal structures, and a recently developed constitutive model will describe the time-dependent, permanent, and stiffness degradation behavior of bone. Models of vertebral trabecular bone specimens and whole vertebrae will be produced using geometry and material property descriptions based on high-resolution micro-CT imaging data, allowing quantitative evaluation of predictive accuracy for specimen-level and whole-bone level failure, and for determining the probability of structural failure with respect to loading history.
Although, initially applied to models to vertebral fractures, these methods have tremendous potential for providing individualized interpretive models to predict fracture risk for the discrete patient with a higher degree of accuracy than large population statistical correlations can provide. Further, this exploratory study will provide important information to guide diagnostic imaging and constitutive model refinements, in order to fully utilize the inherent potential of these probabilistic imaging-based methods.
To develop successful dental restorative materials, a number of material properties and characteristics will be thoroughly evaluated throughout the project. The materials testing core will provide personnel and equipment needed to measure these critical properties. The newly developing resin composites will be based on low shrinkage Bis-acrylate and -methacrylate terminated nematic liquid crystal monomers (NLCM) and a nanofiller which consists of different combinations of silica and metal oxides (Ta2O5, ZrO2). Commercially available materials, which have demonstrated success in in vivo clinical trials, will be used as performance standards, and these will include bis-GMA matrix, and barium silicate particles.
The goal of the materials testing core is to evaluate multiple formulations of the commercially available and newly developing particles and matrices. The NLCM, nanofillers and formulations of the newly developed and commercially available resin composite will be delivered to the testing area labeled with a code known only to the investigator in the research and development core. The tests will be performed in a blind manner in the testing area. The ultimate criteria for selecting NLCM, nanofiller particles, and the newly formulated resin composite will be that properties tested in the developing material formulations must produce results equal to or greater than 80% of a commercially available resin composite. The only exception to this criteria is that polymerization shrinkage must have less than 80% shrinkage of a commercially available resin composite. If the results do not exceed the threshold, the NCLM, nanofiller particles or the newly formulated resin composite and the raw data will be returned to be reformulated. This materials testing core will function as a testing facility only. Thus, the objective of the materials testing core is to guide the evolution, refinement, and fabrication of materials used to develop a novel restorative system throughout its various stages of development.
biomechanics • mechanics and materials • structural integrity • reliability assessment • mechanical behavior • mechanical characterization, fatigue life characterization • crack growth • corrosion fatigue • probabilistic mechanics • uncertainty modeling • bone fracture • bone properties