Radiative transfer equation modeling by streamline diffusion modified continuous Galerkin method.

Optical tomography has a wide range of biomedical applications. Accurate prediction of photon transport in media is critical, as it directly affects the accuracy of the reconstructions. The radiative transfer equation (RTE) is the most accurate deterministic forward model, yet it has not been widely employed in practice due to the challenges in robust and efficient numerical implementations in high dimensions. Herein, we propose a method that combines the discrete ordinate method (DOM) with a streamline diffusion modified continuous Galerkin method to numerically solve RTE. Additionally, a phase function normalization technique was employed to dramatically reduce the instability of the DOM with fewer discrete angular points. To illustrate the accuracy and robustness of our method, the computed solutions to RTE were compared with Monte Carlo (MC) simulations when two types of sources (ideal pencil beam and Gaussian beam) and multiple optical properties were tested. Results show that with standard optical properties of human tissue, photon densities obtained using RTE are, on average, around 5% of those predicted by MC simulations in the entire/deeper region. These results suggest that this implementation of the finite element method-RTE is an accurate forward model for optical tomography in human tissues.

Measurement of lacunar bone strains and crack formation during tensile loading by digital volume correlation of second harmonic generation images.

The maintenance of healthy bone tissue depends upon the ability of osteocytes to respond to mechanical cues on the cellular level. The combination of digital volume correlation and second harmonic generation microscopy offers the opportunity to investigate the mechanical microenvironment of intact bone on the scale of individual osteocytes. Adult human femurs were imaged under tensile loads of 5 and 15MPa and volumes of approximately 492×429×31µm(3) were analyzed, along with an image of a bone microcrack under the same loading conditions. Principal strains were significantly higher in three-dimensional digital volume correlation when compared to two-dimensional digital image correlation. The average maximum principal strain magnitude was 5.06-fold greater than the applied global strain, with peak strains of up to 23.14-fold over global strains measured at the borders of osteocyte lacunae. Finally, a microcrack that initiated at an osteocyte lacunae had its greatest tensile strain magnitudes at the crack expansion front in the direction of a second lacunae, but strain at the crack border was reduced to background strain magnitudes upon breaching the second lacunae. This serveed to demonstrate the role of lacunae in initiating, mediating and terminating microcrack growth.

Stimulation of osteoblast differentiation with guided ultrasound waves.

BACKGROUND: Ultrasound induces mechanical vibration and heat, causing differentiation and proliferation in osteoblasts. All known in vitro evaluations of ultrasound are, however, performed with longitudinal ultrasound waves. We addressed a question: Do other forms of ultrasound waves, such as guided waves (longitudinal and guided flexural) transduced at a remote location, enhance differentiation of osteoblast cells? METHODS: In this study, we employed guided Lamb waves that were induced in a borosilicate glass slide (cortical bone mimic). An average energy of 10-30 mW/cm(2) for 20 min per day was applied to MC3T3 osteoblast-like cells, which were placed 30-75 mm distant from the transducer. RESULTS: The result revealed that guided waves significantly stimulated the differentiation and mineralization of MC3T3 cells. In particular, guided waves elevated mRNA expression levels of bone formation-related genes such as alkaline phosphatase, osteopontin, osteocalcin, osteoprotegerin, and bone sialoprotein on days 8 and 16. In addition, the amount of mineralization found via Alizarin red staining was increased by 157 % (p = 0.034). The amount of mineralization was found to be independent of distance from the transducer (p = 0.967). CONCLUSION: We demonstrate herein that ultrasound in a form of guided Lamb waves is capable of inducing osteoblast differentiation in vitro, and it may enable the stimulation of osteoblasts in vivo over a distance from the site of ultrasound application.

Multilayered Nanoparticles for Gene Delivery Used to Reprogram Human Foreskin Fibroblasts to Neurospheres.

Polycationic nanocomplexes are a robust means for achieving nucleic acid condensation and efficient intracellular gene deliveries. To enhance delivery, a multilayered nanoparticle consisting of a core of electrostatically bound elements was used. These included a histone-mimetic peptides, poly-l-arginine and poly-d-glutamic acid was coated with silicate before surface functionalization with poly-l-arginine. Transfection efficiencies and duration of expression were similar when using green fluorescent protein (GFP) plasmid DNA (pDNA) or GFP mRNA. These nanoparticles demonstrated significantly higher (>100%) and significantly longer (15 vs. 4 days) transfection efficiencies in comparison to a commercial transfection agent (Lipofectamine 2000). Reprogramming of human foreskin fibroblasts using mRNA to the Sox2 transcription factor resulted in three-fold higher neurosphere formation in comparison to the commercial reagent. These results demonstrate the potential of these nanoparticles as ideal vectors for gene delivery.

Combinatorial therapy using negative pressure and varying lithium dosage for accelerated wound healing.

In this work, we investigated the effects of negative pressure, applied using a pump designed for Negative Pressure Wound Therapy (NPWT), on the process of wound healing in vitro via initiation of the Wnt signaling pathway. Results indicate that negative pressure enhanced Wnt signaling and migration into a simulated wound in vitro in NIH-3T3 murine fibroblast cells. Increasing doses of lithium (upto 15 mM) increased basal Wnt signaling and enhanced cell migration into the simulated wound site. A combination of negative pressure and increased doses of lithium synergistically increased Wnt signaling and demonstrated further enhanced cell migration into simulated wound sites, with maximal filling of the simulated wound observed at lithium concentrations of at least 10mM.

Collagen Fibrils in Skin Orient in the Direction of Applied Uniaxial Load in Proportion to Stress while Exhibiting Differential Strains around Hair Follicles.

We determined inhomogeneity of strains around discontinuities as well as changes in orientation of collagen fibrils under applied load in skin. Second Harmonic Generation (SHG) images of collagen fibrils were obtained at different strain magnitudes. Changes in collagen orientation were analyzed using Fast Fourier Transforms (FFT) while strain inhomogeneity was determined at different distances from hair follicles using Digital Image Correlation (DIC). A parameter, defined as the Collagen Orientation Index (COI), is introduced that accounts for the increasingly ellipsoidal nature of the FFT amplitude images upon loading. We show that the COI demonstrates two distinct mechanical regimes, one at low strains (0%, 2.5%, 5% strain) in which randomly oriented collagen fibrils align in the direction of applied deformation. In the second regime, beginning at 5% strain, collagen fibrils elongate in response to applied deformation. Furthermore, the COI is also found to be linearly correlated with the applied stress indicating that collagen fibrils orient to take the applied load. DIC results indicated that major principal strains were found to increase with increased load at all locations. In contrast, minimum principal strain was dependent on distance from hair follicles. These findings are significant because global and local changes in collagen deformations are expected to be changed by disease, and could affect stem cell populations surrounding hair follicles, including mesenchymal stem cells within the outer root sheath.

Rapid and efficient fabrication of multilevel structured silica micro-/nanofibers by centrifugal jet spinning.

A rapid and efficient method consisting of two simple steps, centrifugal jet spinning (CJS) and annealing, is introduced to fabricate multilevel structured silica micro-/nanofibers. Using this technique, which is 500 times faster than electrospinning, silica micro-/nanofibers with a hollow or porous internal structure are formed as a result of non-solvent evaporation induced phase separation in the spinning solution. Silica nanofibers with solid cross sections (364 nm and 781 nm), hollow cross sections (outer and internal diameters of 458 nm and 216 nm respectively), and encapsulated voids (outside diameter of 1.4 µm where bi-continuous nano-pores 118 nm are observed) are fabricated by tuning the amount of non-solvent in the spinning solutions. This technique can be readily extended to large-scale and efficient fabrication of various ceramic materials with multileveled fibrous structures.

Centrifugal Jet Spinning for Highly Efficient and Large-scale Fabrication of Barium Titanate Nanofibers.

The centrifugal jet spinning (CJS) method has been developed to enable large-scale synthesis of barium titanate nanofibers. Barium titanate nanofibers with fiber diameters down to 50 nm and grain sizes around 25 nm were prepared with CJS by spinning a sol-gel solution of barium titanate and poly(vinylpyrrolidone) with subsequent heat treatment at 850 °C. XRD and FTIR analysis demonstrated high purity and tetragonal perovskite structured barium titanate nanofibers. SEM and TEM images confirm the continuous high aspect ratio structure of barium titanate nanofibers after heat treatment. It is demonstrated that the CJS technique offers a highly efficient method for large-scale fabrication of ceramic nanofibers at production rates of up to 0.3 gram/minute.

Magnitude of loads influences the site of failure of highly curved bones.

The structure and material properties of bones along with applied boundary conditions determine the region of peak stresses, where fracture is expected to occur. As the site of peak stresses is not influenced by the magnitude of applied load, the fracture site is not expected to change during fatigue loading of whole bone at different loads. However, in a highly curved bone such as the rat ulna, the magnitude of applied loads was found to influence the fracture site. Fatigue loading was conducted under load control on intact rat forearms and on excised ulnae. The distance to the site of failure from the proximal olecranon process of ulnae was determined. In intact forearms, the site of failure demonstrated a linear progression distally, towards sites with lower moment of inertia (or sites exhibiting lower section modulus). Intact rat forearms and excised ulnae loaded to failure at low loads fractured 2-3mm distal to where they failed when applying high loads. This indicates a shift in the site of failure by approximately 10% of whole bone length just by varying the applied load magnitude. The site of failure in excised ulnae was similar when loading at 2Hz or at 4Hz, suggesting that this was frequency independent in this range and indicating that strain rate was not an important contributing factor. Creep loading of excised ulnae also demonstrated similar changes in the site of failure, indicating that magnitude of loads, and not type of loading were important in determining the site of failure. This has important implications with regards to the volume of bone that undergoes damage under physiological loading, before it fails.

Measuring strain using digital image correlation of second harmonic generation images.

The micromechanical environment of bone is crucial to understanding both bone fracture and mechanobiological responses of osteocytes, yet few techniques exist that are capable of measuring strains on the micrometer scale. A method for measuring micrometer level strains has been developed based on digital image correlation (DIC) of second harmonic generation microscopy (SHGM) images. Bovine tibias milled into thin sections were imaged using SHGM under loads of 0 and 15 MPa. Strains were measured using DIC and compared to applied strain values. First and second principal strains decreased in magnitude as the analysis region area increased from 1750 µm(2) to 60,920 µm(2), converging to 1.23 ± 0.74 and -0.745 ± 0.9816 times the applied strain respectively. A representative sample histogram revealed regions of pure tensile and compressive strain, and that strains were highly heterogeneous ranging from 8410 to -8840 microstrain for an applied 2870 microstrain. Comparison with applied strain measures suggested that analysis sizes of 1750 µm(2) and greater were measuring strains on the tissue scale, and higher resolution is required for collagen fibrillar strains. Regions of low SHGM intensity ("dark" regions) were seen which are believed to be lacunar and perilacunar regions of low collagen density. However, no significant differences in strain magnitude were present in dark regions versus regions of high signal intensity. The proposed technique is effective for strains on the size order of bone microarchitecture, and would be useful for studies into the mechanical microenvironment during loading. The technique also has potential for in vivo studies in small animal models.

Evaluation of multifunctional polysaccharide hydrogels with varying stiffness for bone tissue engineering.

The use of hydrogels for bone regeneration has been limited due to their inherent low modulus to support cell adhesion and proliferation as well as their susceptibility to bacterial infections at the wound site. To overcome these limitations, we evaluated multifunctional polysaccharide hydrogels of varying stiffness to obtain the optimum stiffness at which the gels (1) induce proliferation of human dermal fibroblasts, human umbilical vascular endothelial cells (HUVECs), and murine preosteoblasts (MC3T3-E1), (2) induce osteoblast differentiation and mineralization, and (3) exhibit an antibacterial activity. Rheological studies demonstrated that the stiffness of hydrogels made of a polysaccharide blend of methylcellulose, chitosan, and agarose was increased by crosslinking the chitosan component to different extents with increasing amounts of genipin. The gelation time decreased (from 210 to 60 min) with increasing genipin concentrations. Proliferation of HUVECs decreased by 10.7 times with increasing gel stiffness, in contrast to fibroblasts and osteoblasts, where it increased with gel stiffness by 6.37 and 7.8 times, respectively. At day 14 up to day 24, osteoblast expression of differentiation markers-osteocalcin, osteopontin-and early mineralization marker-alkaline phosphatase, were significantly enhanced in the 0.5% (w/v) crosslinked gel, which also demonstrated enhanced mineralization by day 25. The antibacterial efficacy of the hydrogels decreased with the increasing degree of crosslinking as demonstrated by biofilm formation experiments, but gels crosslinked with 0.5% (w/v) genipin still demonstrated significant bacterial inhibition. Based on these results, gels crosslinked with 0.5% (w/v) genipin, where 33% of available groups on chitosan were crosslinked, exhibited a stiffness of 502±64.5 Pa and demonstrated the optimal characteristics to support bone regeneration.

Large-scale and highly efficient synthesis of micro- and nano-fibers with controlled fiber morphology by centrifugal jet spinning for tissue regeneration.

PLLA fibrous tissue scaffolds with controlled fiber nanoscale surface roughness are fabricated with a novel centrifugal jet spinning process. The centrifugal jet spinning technique is a highly efficient synthesis method for micron- to nano-sized fibers with a production rate up to 0.5 g min(-1). During the centrifugal jet spinning process, a polymer solution jet is stretched by the centrifugal force of a rotating chamber. By engineering the rheological properties of the polymer solution, solvent evaporation rate and centrifugal force that are applied on the solution jet, polyvinylpyrrolidone (PVP) and poly(l-lactic acid) (PLLA) composite fibers with various diameters are fabricated. Viscosity measurements of polymer solutions allowed us to determine critical polymer chain entanglement limits that allow the generation of continuous fiber as opposed to beads or beaded fibers. Above a critical concentration at which polymer chains are partially or fully entangled, lower polymer concentrations and higher centrifugal forces resulted in thinner fibers. Etching of PVP from the PLLA-PVP composite fibers doped with increasing PVP concentrations yielded PLLA fibers with increasing nano-scale surface roughness and porosity, which increased the fiber hydrophilicity dramatically. Scanning electron micrographs of the etched composite fibers suggest that PVP and PLLA were co-contiguously phase separated within the composite fibers during spinning and nano-scale roughness features were created after the partial etching of PVP. To study the tissue regeneration efficacy of the engineered PLLA fiber matrix, human dermal fibroblasts are used to simulate partial skin graft. Fibers with increased PLLA surface roughness and porosity demonstrated a trend towards higher cell attachment and proliferation.

Design and analysis of a novel mechanical loading machine for dynamic in vivo axial loading.

This paper describes the construction of a loading machine for performing in vivo, dynamic mechanical loading of the rodent forearm. The loading machine utilizes a unique type of electromagnetic actuator with no mechanically resistive components (servotube), allowing highly accurate loads to be created. A regression analysis of the force created by the actuator with respect to the input voltage demonstrates high linear correlation (R(2) = 1). When the linear correlation is used to create dynamic loading waveforms in the frequency (0.5-10 Hz) and load (1-50 N) range used for in vivo loading, less than 1% normalized root mean square error (NRMSE) is computed. Larger NRMSE is found at increased frequencies, with 5%-8% occurring at 40 Hz, and reasons are discussed. Amplifiers (strain gauge, linear voltage displacement transducer (LVDT), and load cell) are constructed, calibrated, and integrated, to allow well-resolved dynamic measurements to be recorded at each program cycle. Each of the amplifiers uses an active filter with cutoff frequency at the maximum in vivo loading frequencies (50 Hz) so that electronic noise generated by the servo drive and actuator are reduced. The LVDT and load cell amplifiers allow evaluation of stress-strain relationships to determine if in vivo bone damage is occurring. The strain gauge amplifier allows dynamic force to strain calibrations to occur for animals of different sex, age, and strain. Unique features are integrated into the loading system, including a weightless mode, which allows the limbs of anesthetized animals to be quickly positioned and removed. Although the device is constructed for in vivo axial bone loading, it can be used within constraints, as a general measurement instrument in a laboratory setting.

Reinforcement of bone cement using zirconia fibers with and without acrylic coating.

Acrylic (polymethylmethacrylate or PMMA) bone cement was modified by the addition of high-strength zirconia fibers with average lengths of 200 microm and diameters of 15 microm or 30 microm. A novel emulsion polymerization process was developed to encapsulate individual fibers in PMMA. Improvements in tensile and compressive properties as well as in fracture toughness were investigated upon incorporation of uncoated and acrylic coated zirconia fibers. Bone cements were reinforced with 2% by volume of the 15 microm diameter and 5% by volume of the 30 microm fibers. Results indicate that elastic modulus and ultimate strength of bone cements reinforced with zirconia fibers were higher than controls, being the largest for cements reinforced with 30 microm diameter fibers. The fracture toughness of the cement increased by 23% and 41% by the addition of 15 microm and 30 microm fibers, respectively. Coating of individual zirconia fibers did not result in improved material properties of bone cements. The use of uncoated or acrylic coated 30 microm fibers is recommended based on the significant increases in ultimate strength and fracture toughness of the cements.

High frequency ultrasound prediction of mechanical properties of cortical bone with varying amount of mineral content.

In this study, we evaluate if high frequency ultrasound impedance measurements can predict the mechanical properties of bones where the amount of bone mineral is varied. The motivation stems from the potential utility of ultrasound as a noninvasive technique to evaluate and monitor the mechanical properties of bone during treatment of diseased states where the ratio of mineral content to organic matrix content could change (e.g., metabolic bone diseases, osteoarthritis, osteogenesis imperfecta, fracture healing). Eleven cortical bovine femur samples, which were taken along the long axis of femur, were used in each group. Bone samples with reduced mineral content (estimated to be 21% and 35% less than the control) were obtained by immersing samples into fluoride ion solution for 3 and 12 d. Control and fluoride treated samples were first tested mechanically in tension. Acoustic impedances of the mechanically tested samples were obtained by using scanning acoustic microscopy (SAM). Results from mechanical tests indicate that the tensile elastic modulus of the samples was highly correlated to the yield strength (r(2) = 0.94, p < 0.01) and to the ultimate strength (r(2) = 0.75, p < 0.01). SAM results indicate that the acoustic impedances were significantly correlated to the elastic modulus (r(2) = 0.85, p < 0.01), yield strength (r(2) = 0.86, p < 0.01) and ultimate strength (r(2) = 0.70, p < 0.01). These results show that ultrasonic techniques could potentially be used to predict the in vivo ultimate strength of bone tissue caused by changes in mineral content.

Properties of silorane-based dental resins and composites containing a stress-reducing monomer.

OBJECTIVE: To evaluate properties of silorane-based resins and composites containing a stress reducing monomer. METHODS: Resin mixtures and composites were formulated containing (a) a developmental stress reducing monomer [TOSU; Midwest Research Institute]; (b) Sil-Mix (3M-ESPE); (c) photo cationic initiator system. Standard BISGMA/TEGDMA resin (B/T) and composite (Filtek Z250) were used as controls. Polymerization volume change was measured using a NIST mercury dilatometer and polymerization stress using an Enduratec mechanical testing machine. Three point bend tests determined flexural elastic modulus, work of fracture, and ultimate strength (ADA 27; ISO 4049). Fracture toughness was measured using ASTM E399-90. Four groups of resins and composites were tested: Sil-Mix, methacrylate standard, and Sil-Mix with two addition levels of TOSU. An ANOVA was used and significant differences ranked using Student-Newman-Keuls test (alpha=0.05). RESULTS: Polymerization stress values for resins containing TOSU were significantly less than the other materials. Polymerization shrinkage values for Sil-Mix formulations were significantly less than for B/T, but were not different from each other. TOSU-containing formulations generally had somewhat lower mechanical properties values than Sil-Mix or B/T. Polymerization stress values for Sil-Mix-based composites were significantly less as compared to Z250. The 1wt.% TOSU composite had the lowest stress. No difference between composite groups was noted for fracture toughness or work of fracture. For ultimate strength, the 5wt.% TOSU formulation differed significantly from Z250. All Sil-Mix formulations had elastic modulus values significantly different from Z250. SIGNIFICANCE: The ability of TOSU to reduce polymerization stress without a proportional reduction in mechanical properties provides a basis for improvement of silorane-based composites.

E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation.

Within mineralized bone, osteocytes form dendritic processes that travel through canaliculi to make contact with other osteocytes and cells on the bone surface. This three-dimensional syncytium is thought to be necessary to maintain viability, cell-to-cell communication, and mechanosensation. E11/gp38 is the earliest osteocyte-selective protein to be expressed as the osteoblast differentiates into an osteoid cell or osteocyte, first appearing on the forming dendritic processes of these cells. Bone extracts contain large amounts of E11, but immunostaining only shows its presence in early osteocytes compared to more deeply embedded cells, suggesting epitope masking by mineral. Freshly isolated primary osteoblasts are negative for E11 expression but begin to express this protein in culture, and expression increases with time, suggesting differentiation into the osteocyte phenotype. Osteoblast-like cell lines 2T3 and Oct-1 also show increased expression of E11 with differentiation and mineralization. E11 is highly expressed in MLO-Y4 osteocyte-like cells compared to osteoblast cell lines and primary osteoblasts. Differentiated, mineralized 2T3 cells and MLO-Y4 cells subjected to fluid flow shear stress show an increase in mRNA for E11. MLO-Y4 cells show an increase in dendricity and elongation of dendrites in response to shear stress that is blocked by small interfering RNA specific to E11. In vivo, E11 expression is also increased by a mechanical load, not only in osteocytes near the bone surface but also in osteocytes more deeply embedded in bone. Maximal expression is observed not in regions of maximal strain but in a region of potential bone remodeling, suggesting that dendrite elongation may be occurring during this process. These data suggest that osteocytes may be able to extend their cellular processes after embedment in mineralized matrix and have implications for osteocytic modification of their microenvironment.

Photopolymerization of developmental monomers for dental cationically initiated matrix resins.

OBJECTIVES: The objectives were to investigate the structure and selected physical properties of products resulting from the photopolymerization of a binary mixture containing an aliphatic dioxirane, 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexane carboxylate (ECHM-ECHC) and a potential expanding monomer, 3,9-bis(oxiranylcyclohexylmethyl)-1,5,7,11-tetraoxaspiro[5.5]undecane (BOCHM-TOSU). METHODS: Reaction mixtures were irradiated with a dental curing lamp at room temperature. Some reactions were quenched prior to gel point. Oligomeric products were separated from unreacted monomers by column chromatography, and analyzed by NMR. Physical properties of polymeric solids were measured using accepted standard methods. Protonation energies for monomers were calculated using semi-empirical quantum mechanical methods. RESULTS: Types of oligomers found included poly(ether)s and poly(carbonate)s. Quantum mechanical calculations indicated preferential attack at the more nucleophilic oxaspirocyclic ring sites. For cured solid polymer samples, the elastic modulus was 2.39 +/- 0.24 GPa and the fracture toughness was 0.73 +/- 0.10 MPa m(1/2). These values were similar to those measured for a cured conventional BISGMA/TEGDMA matrix resin. SIGNIFICANCE: The room-temperature photopolymerization of an aliphatic dioxirane and a potential expanding monomer demonstrates the possibility of making cross-linked copolymer resins with improved polymerization shrinkage characteristics for use in dental composites.

Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo.

Dentin matrix protein 1 (DMP1) is highly expressed in osteocytes and is mechanically responsive. To study osteocyte-specific and mechanically regulated DMP1 gene expression, the transcriptional activity of three cis-regulatory regions was first examined in an osteoblast differentiation model in vitro using a green fluorescent protein (GFP) reporter. Expression of the -9624 to +1996 bp (10 kb) and -7892 to +4439 bp (8 kb) DMP1 cis-regulatory regions dramatically increased in areas of mineralized matrix, in dendritic, osteocyte-like cells. Mineralizing cultures expressing the 8-kb construct show dramatic GFP increases in response to loading in cells with a dendritic morphology. Transgenic mice expressing the 8-kb DMP1-GFP and -2433 to +4439 bp (2.5 kb) DMP1-LacZ were generated. Osteocyte-specific expression was found with the 8 kb but not with the 2.5 kb in postnatal animals. However, the 2.5 kb could support expression in rapidly forming osteoblasts and pre-osteocytes in the embryo. Primary calvarial osteoblast cultures demonstrated that the 2.5 kb supports weak expression in a subset of osteoblasts and pre-osteocytes, but not in mature osteocytes. However, the 8 kb supports robust expression in primary bone marrow cultures. Therefore the region -7892 to -2433 bp, termed a 5.5-kb "Osteocyte Enhancer Module," appears to be required for osteocyte specificity. Ulnae of mice with the 8-kb DMP1-GFP were subjected to mechanical loading where GFP expression increased selectively and locally in osteocytes, distal to the mid-shaft and near the surface of the bone. Thus, the 8-kb region of the DMP1 gene is a target for mechanotransduction in osteocytes, and its cis-regulatory activity may be correlated to local strain in bone.

Evaluation of the effects of implant materials and designs on thermal necrosis of bone in cemented hip arthroplasty.

The exothermic polymerization of bone cement may induce thermal necrosis of bone in cemented hip arthroplasty. A finite element formulation was developed to predict the evolution of the temperature with time in the cemented hip replacement system. The developed method is capable of taking into account both the chemical reaction that generates heat during bone cement polymerization (through a kinetic model) and the physical process of heat conduction (with an energy balance equation). The possibility of thermal necrosis of bone was then evaluated based on the temperature history in the bone and an appropriate damage criterion. Specifically, we evaluate the role of implant materials and designs on the thermal response of the system. Results indicated that the peak temperature at the bone/cement interface with a metal prosthesis was lower than that with a polymer or a composite prosthesis in hip replacement systems. Necrosis of bone was predicted to occur with a polymer or a composite prosthesis while no necrosis was predicted with a metal prosthesis in the simulated conditions. When reinforcing osteoporotic hips with injected bone cement in the cancellous core of the femur, the volume of bone cement implanted is increased which may increase the risk of thermal necrosis of bone. We evaluate whether this risk can be decreased through the use of an insulator to contain the bone cement. No thermal necrosis of bone was predicted with a 3 mm thick polyurethane insulator while more damage is predicted for the use of bone cement without the insulator. This method provides a numerical tool for the quantitative simulation of the thermal behavior of bone-cement-prosthesis designs and for examining and refining new designs computationally.