Design Effect of Metallic (Durable) and Polymeric (Resorbable) Stents on Blood Flow and Platelet Activation.

Bioresorbable vascular scaffolds (BVS) provide transient vessel support for occluded coronary arteries while resorbing over time, potentially allowing vessel restoration approximating the native, healthy state. Clinical trials indicate that the Absorb BVS (Abbott Vascular, Santa Clara, CA) performance was similar to that of the Xience metallic drug-eluting stent (DES), with low long-term complications rates. However, when under-deployed in very small vessels (diameter < 2.25 mm), the thrombosis rate of BVS was higher, possibly due to the effect of strut thickness on the hemodynamics (157 µm BVS vs. 81 µm DES). This study aims to determine the influence of BVS design in vessels of varying diameter on the potential platelet activation. Sixteen computational fluid dynamics models of vessels of varying diameter (1.8-3.0 mm), strut thickness (81-157 µm), and BVS/DES designs were compared. Platelet stress accumulation (SA), a metric for the activation potential, was calculated along platelet flow trajectories and their probability distribution was compared. The models were consistent with clinical observations, indicating that devices deployed in very small vessels exhibited increased probability for platelet activity as compared to the same devices deployed in nominal sized vessels. Deployment, although with residual stenosis, increased probability for higher SA than in similar diameter straight vessels. Reducing BVS struts thickness while maintaining their pattern improved performance closer to that of DES. Our findings highlight the importance of appropriate vessel sizing and deployment technique for BVS, and may help designing future BVS with thinner struts, ultimately improving performance in very small vessels.

Locations of bone tissue at high risk of initial failure during compressive loading of the human vertebral body.

Knowledge of the location of initial regions of failure within the vertebra - cortical shell, cortical endplates vs. trabecular bone, as well as anatomic location--may lead to improved understanding of the mechanisms of aging, disease and treatment. The overall objective of this study was to identify the location of the bone tissue at highest risk of initial failure within the vertebral body when subjected to compressive loading. Toward this end, micro-CT-based 60-micron voxel-sized, linearly elastic, finite element models of a cohort of thirteen elderly (age range: 54-87 years, 75+/-9 years) female whole vertebrae without posterior elements were virtually loaded in compression through a simulated disc. All bone tissues within each vertebra having either the maximum or minimum principal strain beyond its 90th percentile were defined as the tissue at highest risk of initial failure within that particular vertebral body. Our results showed that such high-risk tissue first occurred in the trabecular bone and that the largest proportion of the high-risk tissue also occurred in the trabecular bone. The amount of high-risk tissue was significantly greater in and adjacent to the cortical endplates than in the mid-transverse region. The amount of high-risk tissue in the cortical endplates was comparable to or greater than that in the cortical shell regardless of the assumed Poisson's ratio of the simulated disc. Our results provide new insight into the micromechanics of failure of trabecular and cortical bone within the human vertebra, and taken together, suggest that, during strenuous compressive loading of the vertebra, the tissue near and including the endplates is at the highest risk of initial failure.

A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover.

This study addressed the effects of changes in trabecular microarchitecture induced by suppressed bone turnover-including changes to the remodeling space-on the trabecular bone strength-volume fraction characteristics independent of changes in tissue material properties. Twenty female beagle dogs, aged 1-2 years, were treated daily with either oral saline (n=10 control) or high doses of oral risedronate (0.5mg/kg/day, n=10 suppressed) for a period of 1 year, the latter designed (and confirmed) to substantially suppress bone turnover. High-resolution micro-CT-based finite element models (18-mum voxel size) of canine trabecular bone cores (n=2 per vertebral body) extracted from the T-10 vertebrae were analyzed in both compressive and torsional loading cases. The same tissue-level material properties were used in all models, thus providing measures of tissue-normalized strength due only to changes in the microarchitecture. Suppressed bone turnover resulted in more plate-like architecture with a thicker and more dense trabecular structure, but the relationship between the microarchitectural parameters and volume fraction was unaltered (p>0.05). Though the suppressed group had a greater tissue-normalized strength as compared to the control group (p<0.001) for both compressive and torsional loading, the relationship between tissue-normalized strength and volume fraction was not significantly altered for compression (p>0.13) or torsion (p>0.09). In this high-density, non-osteoporotic animal model, the increases in tissue-normalized strength seen with suppression of bone turnover were entirely commensurate with increases in bone volume fraction and thus, no evidence of microarchitecture-related or "stress-riser" effects which may disproportionately affect strength were found.

Cortical and trabecular load sharing in the human vertebral body.

UNLABELLED: The biomechanical role of the vertebral cortical shell remains poorly understood. Using high-resolution finite element modeling of a cohort of elderly vertebrae, we found that the biomechanical role of the shell can be substantial and that the load sharing between the cortical and trabecular bone is complex. As a result, a more integrative measure of the trabecular and cortical bone should improve noninvasive assessment of fracture risk and treatments. INTRODUCTION: A fundamental but poorly understood issue in the assessment of both osteoporotic vertebral fracture risk and effects of treatment is the role of the trabecular bone and cortical shell in the load-carrying capacity of the vertebral body. MATERIALS AND METHODS: High-resolution microCT-based finite element models were developed for 13 elderly human vertebrae (age range: 54-87 years; 74.6 +/- 9.4 years), and parameter studies-with and without endplates-were performed to determine the role of the shell versus trabecular bone and the effect of model assumptions. RESULTS: Across vertebrae, whereas the average thickness of the cortical shell was only 0.38 +/- 0.06 mm, the shell mass fraction (shell mass/total bone mass)-not including the endplates-ranged from 0.21 to 0.39. The maximum load fraction taken by the shell varied from 0.38 to 0.54 across vertebrae and occurred at the narrowest section. The maximum load fraction taken by the trabecular bone varied from 0.76 to 0.89 across vertebrae and occurred near the endplates. Neither the maximum shell load fraction nor the maximum trabecular load fraction depended on any of the densitometric or morphologic properties of the vertebra, indicating the complex nature of the load sharing mechanism. The variation of the shell load-carrying capacity across vertebrae was significantly altered by the removal of endplates, although these models captured the overall trend within a vertebra. CONCLUSIONS: The biomechanical role of the thin cortical shell in the vertebral body can be substantial, being about 45% at the midtransverse section but as low as 15% close to the endplates. As a result of the complexity of load sharing, sampling of only midsection trabecular bone as a strength surrogate misses important biomechanical information. A more integrative approach that combines the structural role of both cortical and trabecular bone should improve noninvasive assessment of vertebral bone strength in vivo.

Influence of bone volume fraction and architecture on computed large-deformation failure mechanisms in human trabecular bone.

Large-deformation bending and buckling have long been proposed as failure mechanisms by which the strength of trabecular bone can be affected disproportionately to changes in bone density, and thus may represent an important aspect of bone quality. We sought here to quantify the contribution of large-deformation failure mechanisms on strength, to determine the dependence of these effects on bone volume fraction and architecture, and to confirm that the inclusion of large-deformation effects in high-resolution finite element models improves predictions of strength versus experiment. Micro-CT-based finite element models having uniform hard tissue material properties were created from 54 cores of human trabecular bone taken from four anatomic sites (age = 70+/-11; 24 male, 27 female donors), which were subsequently biomechanically tested to failure. Strength predictions were made from the models first including, then excluding, large-deformation failure mechanisms, both for compressive and tensile load cases. As expected, strength predictions versus experimental data for the large-deformation finite element models were significantly improved (p < 0.001) relative to the small deformation models in both tension and compression. Below a volume fraction of about 0.20, large-deformation failure mechanisms decreased trabecular strength from 5-80% for compressive loading, while effects were negligible above this volume fraction. Step-wise nonlinear multiple regression revealed that structure model index (SMI) and volume fraction (BV/TV) were significant predictors of these reductions in strength (R2 = 0.83, p < 0.03). Even so, some low-density specimens having nearly identical volume fraction and SMI exhibited up to fivefold differences in strength reduction. We conclude that within very low-density bone, the potentially important biomechanical effect of large-deformation failure mechanisms on trabecular bone strength is highly heterogeneous and is not well explained by standard architectural metrics.

Vertebral fragility and structural redundancy.

The mechanisms of age-related vertebral fragility remain unclear, but may be related to the degree of "structural redundancy" of the vertebra; ie, its ability to safely redistribute stress internally after local trabecular failure from an isolated mechanical overload. To better understand this issue, we performed biomechanical testing and nonlinear micro-CT-based finite element analysis on 12 elderly human thoracic ninth vertebral bodies (age 76.9 ± 10.8 years). After experimentally overloading the vertebrae to measure strength, we used nonlinear finite element analysis to estimate the amount of failed tissue and understand the failure mechanisms. We found that the amount of failed tissue per unit bone mass decreased with decreasing bone volume fraction (r(2) = 0.66, p < 0.01). Thus, for the weak vertebrae with low bone volume fraction, overall failure of the vertebra occurred after failure of just a tiny proportion of the bone tissue (<5%). This small proportion of failed tissue had two sources: the existence of fewer vertically oriented load paths to which load could be redistributed from failed trabeculae; and the vulnerability of the trabeculae in these few load paths to undergo bending-type failure mechanisms, which further weaken the bone. Taken together, these characteristics suggest that diminished structural redundancy may be an important aspect of age-related vertebral fragility: vertebrae with low bone volume fraction are highly susceptible to collapse because so few trabeculae are available for load redistribution if the external loads cause any trabeculae to fail.

The influence of boundary conditions and loading mode on high-resolution finite element-computed trabecular tissue properties.

A widely used technique for determining the material properties of trabecular tissue is to perform combined experimental and computational testing of trabecular structures in order to calibrate effective tissue properties. To better understand the nature of such properties, we tested n=25 cores of human vertebral trabecular bone under two different boundary conditions (endcap and PMMA embedding) and loading modes (compression and torsion). High-resolution (20 microm) finite element models that explicitly modeled the different experimental conditions were constructed and sensitivity studies were performed to quantify errors arising from uncertainties between model and experiment. Mean (+/-S.D.) effective tissue modulus for the four groups ranged from 9.6+/-1.9 to 11.5+/-3.5 GPa, and the overall mean was 10.3+/-2.4 GPa. For the endcap tests, mean values were the same regardless of loading mode, suggesting that the effective tissue modulus is representative of true material behavior. However, on a specimen-specific basis, the various repeated measures of effective tissue modulus were only moderately correlated with each other (R2=27% to 81%), indicating that the individual measures can be subject to appreciable random errors. The sensitivity studies on the endcap tests indicated that models using lower resolution (40 microm element size) and roller-type platens boundary conditions overestimated effective tissue modulus by 42% on average, although preliminary tests with higher-density femoral neck bone indicated less sensitivity to modeling issues. We conclude that effective tissue properties derived from micro-finite element models do have biomechanical significance if measured correctly, although individual measures of tissue properties may have poor precision.

Multi-scale modeling of the human vertebral body: comparison of micro-CT based high-resolution and continuum-level models.

The overall goal of this study was to assess the mechanistic fidelity of continuum-level finite element models of the vertebral body, which represent a promising tool for understanding and predicting clinical fracture risk. Two finite element (FE) models were generated from micro-CT scans of each of 13 T9 vertebral bodies--a micro-FE model at 60-micron resolution and a coarsened, continuum-level model at 0.96-mm resolution. Two previously-reported continuum-level modulus-density relationships for human vertebral bone were parametrically varied to investigate their effects on model fidelity using the micro-CT models as a gold standard. We found that the modulus-density relation, particularly that assigned to the peripheral bone, substantially altered the regression coefficients, but not the degree of correlation between continuum and micro-FE predictions of whole-vertebral stiffness. The major load paths through the vertebrae compared well between the continuum-level and micro-FE models (von-Mises distribution), but the distributions of minimum principal strain were notably different. We conclude that continuum-level models provide robust measures of whole-vertebral behavior, describe well the load transfer paths through the vertebra, but provide strain distributions that are markedly different than the volume-averaged micro-scale strains. Appreciation of these multi-scale differences should improve interpretation of results from these sorts of continuum models and may improve their clinical utility.

Role of trabecular microarchitecture in whole-vertebral body biomechanical behavior.

The role of trabecular microarchitecture in whole-vertebral biomechanical behavior remains unclear, and its influence may be obscured by such factors as overall bone mass, bone geometry, and the presence of the cortical shell. To address this issue, 22 human T(9) vertebral bodies (11 female; 11 male; age range: 53-97 yr, 81.5 +/- 9.6 yr) were scanned with microCT and analyzed for measures of trabecular microarchitecture, BMC, cross-sectional area, and cortical thickness. Sixteen of the vertebrae were biomechanically tested to measure compressive strength. To estimate vertebral compressive stiffness with and without the cortical shell for all 22 vertebrae, two high-resolution finite element models per specimen-one intact model and one with the shell removed-were created from the microCT scans and virtually compressed. Results indicated that BMC and the structural model index (SMI) were the individual parameters most highly associated with strength (R(2) = 0.57 each). Adding microarchitecture variables to BMC in a stepwise multiple regression model improved this association (R(2) = 0.85). However, the microarchitecture variables in that regression model (degree of anisotropy, bone volume fraction) differed from those when BMC was not included in the model (SMI, mean trabecular thickness), and the association was slightly weaker for the latter (R(2) = 0.76). The finite element results indicated that the physical presence of the cortical shell did not alter the relationships between microarchitecture and vertebral stiffness. We conclude that trabecular microarchitecture is associated with whole-vertebral biomechanical behavior and that the role of microarchitecture is mediated by BMC but not by the cortical shell.

Effects of suppression of bone turnover on cortical and trabecular load sharing in the canine vertebral body.

The relative biomechanical effects of antiresorptive treatment on cortical thickness vs. trabecular bone microarchitecture in the spine are not well understood. To address this, T-10 vertebral bodies were analyzed from skeletally mature female beagle dogs that had been treated with oral saline (n=8 control) or a high dose of oral risedronate (0.5mg/kg/day, n=9 RIS-suppressed) for 1 year. Two linearly elastic finite element models (36-mum voxel size) were generated for each vertebral body-a whole-vertebra model and a trabecular-compartment model-and subjected to uniform compressive loading. Tissue-level material properties were kept constant to isolate the effects of changes in microstructure alone. Suppression of bone turnover resulted in increased stiffness of the whole vertebra (20.9%, p=0.02) and the trabecular compartment (26.0%, p=0.01), while the computed stiffness of the cortical shell (difference between whole-vertebra and trabecular-compartment stiffnesses, 11.7%, p=0.15) was statistically unaltered. Regression analyses indicated subtle but significant changes in the relative structural roles of the cortical shell and the trabecular compartment. Despite higher average cortical shell thickness in RIS-suppressed vertebrae (23.1%, p=0.002), the maximum load taken by the shell for a given value of shell mass fraction was lower (p=0.005) for the RIS-suppressed group. Taken together, our results suggest that-in this canine model-the overall changes in the compressive stiffness of the vertebral body due to suppression of bone turnover were attributable more to the changes in the trabecular compartment than in the cortical shell. Such biomechanical studies provide an unique insight into higher-scale effects such as the biomechanical responses of the whole vertebra.