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Aiyangar, A. K., Vivanco, J., Au, A. G., Anderson, P. A., Smith, E. L., & Ploeg, H. L. (2014). Dependence of Anisotropy of Human Lumbar Vertebral Trabecular Bone on Quantitative Computed Tomography-Based Apparent Density. J. Biomech. Eng.-Trans. ASME, 136(9), 10 pp.
Abstract: Most studies investigating human lumbar vertebral trabecular bone (HVTB) mechanical property-density relationships have presented results for the superior-inferior (SI), or “ on-axis” direction. Equivalent, directly measured data from mechanical testing in the transverse (TR) direction are sparse and quantitative computed tomography (QCT) density-dependent variations in the anisotropy ratio of HVTB have not been adequately studied. The current study aimed to investigate the dependence of HVTB mechanical anisotropy ratio on QCT density by quantifying the empirical relationships between QCT-based apparent density of HVTB and its apparent compressive mechanical propertieselastic modulus (E-app), yield strength (sigma(y)), and yield strain (epsilon(y))-in the SI and TR directions for future clinical QCT-based continuum finite element modeling of HVTB. A total of 51 cylindrical cores (33 axial and 18 transverse) were extracted from four L1 human lumbar cadaveric vertebrae. Intact vertebrae were scanned in a clinical resolution computed tomography (CT) scanner prior to specimen extraction to obtain QCT density, rho(CT). Additionally, physically measured apparent density, computed as ash weight over wet, bulk volume, rho(app), showed significant correlation with rho(CT) [rho(CT) = 1.0568 x rho(app), r = 0.86]. Specimens were compression tested at room temperature using the Zetos bone loading and bioreactor system. Apparent elastic modulus (E-app) and yield strength (sigma(y)) were linearly related to the rho(CT) in the axial direction [E-SI = 1493.8 x (rho(CT)), r = 0.77, p < 0.01; sigma(Y,SI) = 6.9 x (rho(CT)) = 0.13, r = 0.76, p < 0.01] while a power-law relation provided the best fit in the transverse direction [E-TR 3349.1 x (rho(CT))(1.94), r = 0.89, p < 0.01; sigma(Y,TR) 18.81 x (rho(CT)) 1.83, r = 0.83, p < 0.01]. No significant correlation was found between epsilon(y) and rho(CT) in either direction. E-app and sigma(y) in the axial direction were larger compared to the transverse direction by a factor of 3.2 and 2.3, respectively, on average. Furthermore, the degree of anisotropy decreased with increasing density. Comparatively, epsilon(y) exhibited only a mild, but statistically significant anisotropy: transverse strains were larger than those in the axial direction by 30%, on average. Ability to map apparent mechanical properties in the transverse direction, in addition to the axial direction, from CT-based densitometric measures allows incorporation of transverse properties in finite element models based on clinical CT data, partially offsetting the inability of continuum models to accurately represent trabecular architectural variations.
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Collins, C. J., Vivanco, J. F., Sokn, S. A., Williams, B. O., Burgers, T. A., & Ploeg, H. L. (2015). Fracture healing in mice lacking Pten in osteoblasts: a micro-computed tomography image-based analysis of the mechanical properties of the femur. J. Biomech., 48(2), 310–317.
Abstract: In the United States, approximately eight million osseous fractures are reported annually, of which 5-10% fail to create a bony union. Osteoblast-specific deletion of the gene Pten in mice has been found to stimulate bone growth and accelerate fracture healing. Healing rates at four weeks increased in femurs from Pten osteoblast conditional knock-out mice (Pten-CKO) compared to wild-type mice (WT) of the same genetic strain as measured by an increase in mechanical stiffness and failure load in four-point bending tests. Preceding mechanical testing, each femur was imaged using a Skyscan 1172 micro-computed tomography (mu CT) scanner (Skyscan, Kontich, Belgium). The present study used μCT image-based analysis to test the hypothesis that the increased femoral fracture force and stiffness in Pten-CKO were due to greater section properties with the same effective material properties as that of the WT. The second moment of area and section modulus were computed in ImageJ 1.46 (National Institutes of Health) and used to predict the effective flexural modulus and the stress at failure for fourteen pairs of intact and callus WT and twelve pairs of intact and callus Pten-CKO femurs. For callus and intact femurs, the failure stress and tissue mineral density of the Pten-CKO and WT were not different; however, the section properties of the Pten-CKO were more than twice as large 28 days post-fracture. It was therefore concluded, when the gene Pten was conditionally knocked-out in osteoblasts, the resulting increased bending stiffness and force to fracture were due to increased section properties. (C) 2014 Elsevier Ltd. All rights reserved.
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Contreras-Raggio, J. I., Arancibia, C. T., Millan, C., Ploeg, H. L., Aiyangar, A., & Vivanco, J. F. (2022). Height-to-Diameter Ratio and Porosity Strongly Influence Bulk Compressive Mechanical Properties of 3D-Printed Polymer Scaffolds. Polymers, 14(22), 5017.
Abstract: Although the architectural design parameters of 3D-printed polymer-based scaffolds-porosity, height-to-diameter (H/D) ratio and pore size-are significant determinants of their mechanical integrity, their impact has not been explicitly discussed when reporting bulk mechanical properties. Controlled architectures were designed by systematically varying porosity (30-75%, H/D ratio (0.5-2.0) and pore size (0.25-1.0 mm) and fabricated using fused filament fabrication technique. The influence of the three parameters on compressive mechanical properties-apparent elastic modulus E-app, bulk yield stress sigma(y) and yield strain epsilon(y)-were investigated through a multiple linear regression analysis. H/D ratio and porosity exhibited strong influence on the mechanical behavior, resulting in variations in mean E-app of 60% and 95%, respectively. sigma(y) was comparatively less sensitive to H/D ratio over the range investigated in this study, with 15% variation in mean values. In contrast, porosity resulted in almost 100% variation in mean sigma(y) values. Pore size was not a significant factor for mechanical behavior, although it is a critical factor in the biological behavior of the scaffolds. Quantifying the influence of porosity, H/D ratio and pore size on bench-top tested bulk mechanical properties can help optimize the development of bone scaffolds from a biomechanical perspective.
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Meyer, L. A., Johnson, M. G., Cullen, D. M., Vivanco, J. F., Blank, R. D., Ploeg, H. L., et al. (2016). Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis. Bone, 85, 115–122.
Abstract: Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-1 (big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2 x 2 factorial trial of daily mechanical loading (-2000 μepsilon,120 cycles daily, “jump” waveform) and big ET1 (25 ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23 days. The bone cores' response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (Delta E-app), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher's LSD test found no significant treatment effects on Delta E-app (p = 0.25 and 0.51 for load and big ET1, respectively). The Delta E-app in the “no load + big ET1” (CE, 13 +/- 12.2%, p = 0.56), “load + no big ET1” (LC, 17 +/- 3.9%, p = 0.14) and “load + big ETI” (LE, 19 +/- 4.2%, p = 0.13) treatment groups were not statistically different than the control group (CC, 3.3% +/- 8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (p = 0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (p = 0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (p = 0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (p = 0.037, p = 0.055 respectively) and MAR (p = 0.0040, p = 0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (p = 0.019) and LC (p = 0.074) than CC. The PGE2 levels were elevated at 8 days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15,19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses. (C) 2016 Elsevier Inc. All rights reserved.
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Slane, J., Vivanco, J., Ebenstein, D., Squire, M., & Ploeg, H. L. (2014). Multiscale characterization of acrylic bone cement modified with functionalized mesoporous silica nanoparticles. J. Mech. Behav. Biomed. Mater., 37, 141–152.
Abstract: Acrylic bone cement is widely used to anchor orthopedic implants to bone and mechanical failure of the cement mantle surrounding an implant can contribute to aseptic loosening. In an effort to enhance the mechanical properties of bone cement, a variety of nanoparticles and fibers can be incorporated into the cement matrix. Mesoporous silica nanoparticles (MSNs) are a class of particles that display high potential for use as reinforcement within bone cement. Therefore, the purpose of this study was to quantify the impact of modifying an acrylic cement with various low-loadings of mesoporous silica. Three types of MSNs (one plain variety and two modified with functional groups) at two loading ratios (0.1 and 0.2 wt/wt) were incorporated into a commercially available bone cement. The mechanical properties were characterized using four-point bending, microindentation and nanoindentation (static, stress relaxation, and creep) while material properties were assessed through dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis, FTIR spectroscopy, and scanning electron microscopy. Four-point flexural testing and nanoindentation revealed minimal impact on the properties of the cements, except for several changes in the nano-level static mechanical properties. Conversely, microindentation testing demonstrated that the addition of MSNs significantly increased the microhardness. The stress relaxation and creep properties of the cements measured with nanoindentation displayed no effect resulting from the addition of MSNs. The measured material properties were consistent among all cements. Analysis of scanning electron micrographs images revealed that surface functionalization enhanced particle dispersion within the cement matrix and resulted in fewer particle agglomerates. These results suggest that the loading ratios of mesoporous silica used in this study were not an effective reinforcement material. Future work should be conducted to determine the impact of higher MSN loading ratios and alternative functional groups. (C) 2014 Elsevier Ltd. All rights reserved.
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Slane, J., Vivanco, J., Meyer, J., Ploeg, H. L., & Squire, M. (2014). Modification of acrylic bone cement with mesoporous silica nanoparticles: Effects on mechanical, fatigue and absorption properties. J. Mech. Behav. Biomed. Mater., 29, 451–461.
Abstract: Polymethyl methacrylate bone cement is the most common and successful method used to anchor orthopedic implants to bone, as evidenced by data from long-term national joint registries. Despite these successes, mechanical failure of the cement mantle can result in premature failure of an implant which has lead to the development of a variety of techniques aimed at enhancing the mechanical properties of the cement, such as the addition of particulate or fiber reinforcements. This technique however has not transitioned into clinical practice, likely due to problems relating to interfacial particle/matrix adhesion and high cement stiffness. Mesoporous silica nanoparticles (MSNs) are a class of materials that have received little attention as polymer reinforcements despite their potential ability to overcome these challenges. Therefore, the objective of the present study was to investigate the use of mesoporous silica nanoparticles (MSNs) as a reinforcement material within acrylic bone cement. Three different MSN loading ratios (0.5%, 2% and 5% (wt/wt)) were incorporated into a commercially available bone cement and the resulting impact on the cement's static mechanical properties, fatigue life and absorption/elution properties were quantified. The flexural modulus and compressive strength and modulus tended to increase with higher MSN concentration. Conversely, the flexural strength, fracture toughness and work to fracture all significantly decreased with increasing MSN content. The fatigue properties were found to be highly influenced by MSNs, with substantial detrimental effects seen with high MSN loadings. The incorporation of 5% MSNs significantly increased cement's hydration degree and elution percentage. The obtained results suggest that the interfacial adhesion strength between the nanoparticles and the polymer matrix was poor, leading to a decrease in the flexural and fatigue properties, or that adequate dispersion of the MSNs was not achieved. These findings could potentially be mitigated in future work by chemically modifying the mesoporous silica with functional groups. (C) 2013 Elsevier Ltd. All rights reserved.
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Slane, J., Vivanco, J., Rose, W., Ploeg, H. L., & Squire, M. (2015). Mechanical, material, and antimicrobial properties of acrylic bone cement impregnated with silver nanoparticles. Mater. Sci. Eng. C-Mater. Biol. Appl., 48, 188–196.
Abstract: Prosthetic joint infection is one of the most serious complications that can lead to failure of a total joint replacement. Recently, the rise of multidrug resistant bacteria has substantially reduced the efficacy of antibiotics that are typically incorporated into acrylic bone cement. Silver nanoparticles (AgNPs) are an attractive alternative to traditional antibiotics resulting from their broad-spectrum antimicrobial activity and low bacterial resistance. The purpose of this study, therefore, was to incorporate metallic silver nanoparticles into acrylic bone cement and quantify the effects on the cement's mechanical, material and antimicrobial properties. AgNPs at three loading ratios (025, 0.5, and 1.0% wt/wt) were incorporated into a commercial bone cement using a probe sonication technique. The resulting cements demonstrated mechanical and material properties that were not substantially different from the standard cement. Testing against Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer and time-kill assays demonstrated no antimicrobial activity against planktonic bacteria. In contrast, cements modified with AgNPs significantly reduced biofilm formation on the surface of the cement. These results indicate that AgNP-loaded cement is of high potential for use in primary arthroplasty where prevention of bacterial surface colonization is vital. (C) 2014 Elsevier B.V. All rights reserved.
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Slane, J., Vivanco, J. F., Squire, M., & Ploeg, H. L. (2017). Characterization of the quasi-static and viscoelastic properties of orthopaedic bone cement at the macro and nanoscale. J. Biomed. Mater. Res. Part B, 105(6), 1461–1468.
Abstract: Acrylic bone cement is often used in total joint replacement procedures to anchor an orthopaedic implant to bone. Bone cement is a viscoelastic material that exhibits creep and stress relaxation properties, which have been previously characterized using a variety of techniques such as flexural testing. Nanoindentation has become a popular method to characterize polymer mechanical properties at the nanoscale due to the technique's high sensitivity and the small sample volume required for testing. The purpose of the present work therefore was to determine the mechanical properties of bone cement using traditional macroscale techniques and compare the results to those obtained from nanoindentation. To this end, the quasi-static and viscoelastic properties of two commercially available cements, Palacos and Simplex, were assessed using a combination of three-point bending and nanoindentation. Quasi-static properties obtained from nanoindentation tended to be higher relative to three-point bending. The general displacement and creep compliance trends were similar for the two methods. These findings suggest that nanoindentation is an attractive characterization technique for bone cement, due to the small sample volumes required for testing. This may prove particularly useful in testing failed/ retrieved cement samples from patients where material availability is typically limited. (C) 2016 Wiley Periodicals, Inc.
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Slane, J. A., Vivanco, J. F., Rose, W. E., Squire, M. W., & Ploeg, H. L. (2014). The influence of low concentrations of a water soluble poragen on the material properties, antibiotic release, and biofilm inhibition of an acrylic bone cement. Mater. Sci. Eng. C-Mater. Biol. Appl., 42, 168–176.
Abstract: Soluble particulate fillers can be incorporated into antibiotic-loaded acrylic bone cement in an effort to enhance antibiotic elution. Xylitol is a material that shows potential for use as a filler due to its high solubility and potential to inhibit biofilm formation. The objective of this work, therefore, was to investigate the usage of low concentrations of xylitol in a gentamicin-loaded cement. Five different cements were prepared with various xylitol loadings (0, 1, 2.5, 5 or 10 g) per cement unit, and the resulting impact on the mechanical properties, cumulative antibiotic release, biofilm inhibition, and thermal characteristics were quantified. Xylitol significantly increased cement porosity and a sustained increase in gentamicin elution was observed in all samples containing xylitol with a maximum cumulative release of 41.3%. Xylitol had no significant inhibitory effect on biofilm formation. All measured mechanical properties tended to decrease with increasing xylitol concentration; however, these effects were not always significant. Polymerization characteristics were consistent among all groups with no significant differences found. The results from this study indicate that xylitol-modified bone cement may not be appropriate for implant fixation but could be used in instances where sustained, increased antibiotic elution is warranted, such as in cement spacers or beads. (C) 2014 Elsevier B.V. All rights reserved.
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Vivanco, J., Jakes, J. E., Slane, J., & Ploeg, H. L. (2014). Accounting for structural compliance in nanoindentation measurements of bioceramic bone scaffolds. Ceram. Int., 40(8), 12485–12492.
Abstract: Structural properties have been shown to be critical in the osteoconductive capacity and strength of bioactive ceramic bone scaffolds. Given the cellular foam-like structure of bone scaffolds, nanoindentation has been used as a technique to assess the mechanical properties of individual components of the scaffolds. Nevertheless, nanoindents placed on scaffolds may violate the rigid support assumption of the standard Oliver-Pharr method currently used in evaluating the Meyer hardness, H, and elastic modulus, E-s, of such structures. Thus, the objective of this research was to use the structural compliance method to assess whether or not specimen-scale flexing may occur during nanoindentation of bioceramic bone scaffolds and to remove the associated artifact on the H and E-s if it did occur. Scaffolds were fabricated using tricalcium phosphate and sintered at 950 degrees C and 1150 degrees C, and nanoindents were placed in three different (center, edge, and corner) scaffold locations. Using only the standard Oliver-Pharr analysis it was found that H and E-s were significantly affected by both sintering temperature and nanoindents location (p < 0.05). However, specimen-scale flexing occurred during nanoindentation in the 1150 degrees C corner location. After removing the effects of the flexing from the measurement using the structural compliance method, it was concluded that H and E-s were affected only by the sintering temperature (p < 0.05) irrespective of the nanoindent locations. These results show that specimen-scale flexing may occur during nanoindentation of components in porous bioceramic scaffolds or in similar structure biomaterials, and that the structural compliance method must be utilized to accurately assess H and E-s of these components. (C) 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
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Vivanco, J. F., Burgers, T. A., Garcia-Rodriguez, S., Crookshank, M., Kunz, M., MacIntyre, N. J., et al. (2014). Estimating the density of femoral head trabecular bone from hip fracture patients using computed tomography scan data. Proc. Inst. Mech. Eng. Part H-J. Eng. Med., 228(6), 616–626.
Abstract: The purpose of this study was to compare computed tomography density (rho(CT)) obtained using typical clinical computed tomography scan parameters to ash density (rho(ash)), for the prediction of densities of femoral head trabecular bone from hip fracture patients. An experimental study was conducted to investigate the relationships between rho(ash) and rho(CT) and between each of these densities and rho(bulk) and rho(dry). Seven human femoral heads from hip fracture patients were computed tomography-scanned ex vivo, and 76 cylindrical trabecular bone specimens were collected. Computed tomography density was computed from computed tomography images by using a calibration Hounsfield units-based equation, whereas rho(bulk), rho(dry) and rho(ash) were determined experimentally. A large variation was found in the mean Hounsfield units of the bone cores (HUcore) with a constant bias from rho(CT) to rho(ash) of 42.5 mg/cm(3). Computed tomography and ash densities were linearly correlated (R-2 = 0.55, p < 0.001). It was demonstrated that rho(ash) provided a good estimate of rho(bulk) (R-2 = 0.78, p < 0.001) and is a strong predictor of rho(dry) (R-2 = 0.99, p < 0.001). In addition, the rho(CT) was linearly related to rho(bulk) (R-2 = 0.43, p < 0.001) and rho(dry) (R-2 = 0.56, p < 0.001). In conclusion, mineral density was an appropriate predictor of rho(bulk) and rho(dry), and rho(CT) was not a surrogate for rho(ash). There were linear relationships between rho(CT) and physical densities; however, following the experimental protocols of this study to determine rho(CT), considerable scatter was present in the rho(CT) relationships.
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