Biomedical subjects

Ralph Müller

Publications and source records attributed to Ralph Müller.

At least 19 recordsLinked to original sources

PubMed2006

Control of in vitro tissue-engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds.

Natural bone consists of cortical and trabecular morphologies, the latter having variable pore sizes. This study aims at engineering different bone-like structures using scaffolds with small pores (112-224 microm) in diameter on one side and large pores (400-500 microm) on the other, while keeping scaffold porosities constant among groups. We hypothesized that tissue engineered bone-like structure resulting from silk fibroin (SF) implants is pre-determined by the scaffolds' geometry. To test this hypothesis, SF scaffolds with different pore diameters were prepared and seeded with human mesenchymal stem cells (hMSC). As compared to static seeding, dynamic cell seeding in spinner flasks resulted in equal cell viability and proliferation, and better cell distribution throughout the scaffold as visualized by histology and confocal microscopy, and was, therefore, selected for subsequent differentiation studies. Differentiation of hMSC in osteogenic cell culture medium in spinner flasks for 3 and 5 weeks resulted in increased alkaline phosphatase activity and calcium deposition when compared to control medium. Micro-computed tomography (microCT) detailed the pore structures of the newly formed tissue and suggested that the structure of tissue-engineered bone was controlled by the underlying scaffold geometry.

Biocompatible Materials↗

PubMed2006

Evaluation of three-dimensional image registration methodologies for in vivo micro-computed tomography.

The advent of in vivo micro-computed tomography (micro-CT) provides a novel approach to measure the temporal adaptation of bone micro-architecture within an individual. Spatial alignment in the scanner between serial scans is challenging, but three-dimensional image registration can be used to superimpose the resulting image data, thus ensuring consistent regions of interest (ROI) for analysis. There have been several approaches to image registration developed, yet little is known about their application to high resolution micro-CT data. The purpose of this study was to explore combinations of three image registration similarity measures and three image interpolators, in addition to multi-resolution registration configurations, for assessment of computational efficiency and accuracy on both in vitro and in vivo micro-CT data. Accuracy measures were assessed by comparison with a gold-standard reference transform based on attached fiducial markers. It was concluded that a mutual information registration similarity measure with a linear image interpolator, applied at steps of increasing image resolution, provided the best compromise between accurate and efficient results. In vivo registration of tibial bone microstructure measured in an ovariectomized rat model provided consistent ROI thus demonstrating the usefulness of three-dimensional image registration for in vivo experimental and clinical micro-CT research. It is a technique that is poised to become commonly utilized for analysis of micro-CT data to diagnose and monitor efficacy of therapy in bone diseases.

Animals↗

PubMed2006

The interaction of microstructure and volume fraction in predicting failure in cancellous bone.

Inroads have been made in the diagnosis and treatment of osteoporosis, yet dual-energy X-ray absorptiometry is still the primary diagnostic modality. This method provides 2D projections of an irregular 3D construct. However, human cancellous bone is highly heterogeneous with varying material properties. Therefore, to properly assess fracture risk, it is imperative to take into consideration microstructural indices besides subregional bone volume fraction (BV/TV). A power law model with average BV/TV as the independent variable describes 38% of the variation in yield strength; however, this predictive power is increased to 56% when BV/TV of the weakest subregion is considered. Of twenty-five specimens studied, 76% had minimum BV/TV, maximum principal Eigen value of the fabric tensor (H1) and minimum connectivity density (Conn.D) values within the visually determined failure regions. These three independent morphometric indices yielded significant differences between the failure and non-failure regions of each specimen. From the results, we conclude that subregions with minimal BV/TV values are better predictors of mechanical failure in cancellous bone than average specimen BV/TV. Addition of microstructural indices augments this predictive power to generate a trabecular failure prediction model based on volume fraction and cancellous bone microstructure specifically in areas where trabecular failure is most likely to occur.

Aged↗

PubMed2006

In vivo behavior of calcium phosphate scaffolds with four different pore sizes.

The goal of the present study was to assess the effect of macropore size on the in vivo behavior of ceramic scaffolds. For that purpose, beta-tricalcium phosphate (beta-TCP) cylinders with four different macropore sizes (150, 260, 510, and 1220 microm) were implanted into drill hole defects in cancellous bone of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The scaffolds were evaluated for biocompatibility, and new bone formation was observed macroscopically, histologically and histomorphometrically. Histomorphometrical measurements were performed for the whole defect area and for the area subdivided into three concentric rings (outer, medial, and inner ring). All implants were tolerated very well as evidenced by the low amount of inflammatory cells and the absence of macroscopic signs of inflammation. Resorption proceeded fast since less than 5% ceramic remained at 24-week implantation. Hardly any effect of macropore size was observed on the in vivo response. Samples with an intermediate macropore size (510 microm) were resorbed significantly faster than samples with smaller macropore sizes (150 and 260 microm). However, this fast resorption was associated with a lower bone content and a higher soft tissue content. At 12 and 24 weeks, the latter differences had disappeared. Bone was more abundant in the outer ring than in the rest of the blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at 12 weeks.

Animals↗

PubMed2006

Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling.

The CB1 cannabinoid receptor has been implicated in the regulation of bone remodeling and bone mass. A high bone mass (HBM) phenotype was reported in CB1-null mice generated on a CD1 background (CD1(CB1-/-) mice). By contrast, our preliminary studies in cb1-/- mice, backcrossed to C57BL/6J mice (C57(CB1-/-) mice), revealed low bone mass (LBM). We therefore analyzed CB1 expression in bone and compared the skeletons of sexually mature C57(CB1-/-) and CD1(CB1-/-) mice in the same experimental setting. CB1 mRNA is weakly expressed in osteoclasts and immunoreactive CB1 is present in sympathetic neurons, close to osteoblasts. In addition to their LBM, male and female C57(CB1-/-) mice exhibit decreased bone formation rate and increased osteoclast number. The skeletal phenotype of the CD1(CB1-/-) mice shows a gender disparity. Female mice have normal trabecular bone with a slight cortical expansion, whereas male CD1(CB1-/-) animals display an HBM phenotype. We were surprised to find that bone formation and resorption are within normal limits. These findings, at least the consistent set of data obtained in the C57(CB1-/-) line, suggest an important role for CB1 signaling in the regulation of bone remodeling and bone mass. Because sympathetic CB1 signaling inhibits norepinephrine (NE) release in peripheral tissues, part of the endocannabinoid activity in bone may be attributed to the regulation of NE release from sympathetic nerve fibers. Several phenotypic discrepancies have been reported between C57(CB1-/-) and CD1(CB1-/-) mice that could result from genetic differences between the background strains. Unraveling these differences can provide useful information on the physiologic functional milieu of CB1 in bone.

Adrenergic Fibers↗

PubMed2006

Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography.

The ovariectomized (OVX) rat is a well established model for osteoporosis research. The recent development of in vivo micro-computed tomography (micro-CT) provides new possibilities to monitor individual bone changes over time. The purpose of this study was to establish the normal time course of bone loss in the OVX rat model, and to determine the ability to detect morphological changes in vivo compared to cross-sectional study designs where animals are sacrificed at each time point. Eight-month-old female Wistar rats were randomly assigned to one of two groups: OVX (N = 10) or sham-operated (N = 10). In vivo micro-CT scanning of the right proximal tibial metaphyses occurred at 1-month intervals for 6 months. Morphological analyses were performed at each time step for every animal, and a two-way ANOVA with repeated measures was used to analyze the data. A second statistical analysis was performed without repeated measures for analysis as a cross-sectional study design. The repeated measures analysis was more sensitive to early changes than the cross-sectional study analysis. Changes were detected by longitudinal analysis in the sham-operated and OVX animals over time (P < 0.001) with the exception of trabecular separation in the sham animals. The OVX animals had decreases of bone volume ratio of 33% after 1 month, and 72% after 3 months relative to baseline measurements. Significant changes in bone volume ratio, trabecular number and separation were detected early using a longitudinal analysis, thus in vivo assessment is well poised to enable the study of early treatment protocols on the effects of bone architecture. The in vivo analysis found significant changes in the sham animals which were not detected by the cross-sectional analysis, and the changes to the OVX animal morphology was detected sooner. A substantial variation of baseline morphometry within the homogenous group of rats and response to OVX was observed, thus emphasizing the advantage of performing in vivo analysis where each animal acts as its own control. These data provide new insight into individual bone changes following OVX, and can be used as baseline information upon which future in vivo studies can be designed.

Age Factors↗

PubMed2006

Hierarchical microimaging for multiscale analysis of large vascular networks.

There is a wide range of diseases and normal physiological processes that are associated with alterations of the vascular system in organs. Ex vivo imaging of large vascular networks became feasible with recent developments in microcomputed tomography (microCT). Current methods permit to visualize only limited numbers of physically excised regions of interests (ROIs) from larger samples. We developed a method based on modified vascular corrosion casting (VCC), scanning electron microscopy (SEM), and desktop and synchrotron radiation microCT (SRmicroCT) technologies to image vasculature at increasing levels of resolution, also referred to as hierarchical imaging. This novel approach allows nondestructive 3D visualization and quantification of large microvascular networks, while retaining a precise anatomical context for ROIs scanned at very high resolution. Scans of entire mouse brain VCCs were performed at 16-microm resolution with a desktop microCT system. Custom-made navigation software with a ROI selection tool enabled the identification of anatomical brain structures and precise placement of multiple ROIs. These were then scanned at 1.4-microm voxel size using SRmicroCT and a local tomography setup. A framework was developed for fast sample positioning, precise selection of ROIs, and sequential high-throughput scanning of a large numbers of brain VCCs. Despite the use of local tomography, exceptional image quality was achieved with SRmicroCT. This method enables qualitative and quantitative assessment of vasculature at unprecedented resolution and volume with relatively high throughput, opening new possibilities to study vessel architecture and vascular alterations in models of disease.

Animals↗

PubMed2006

Parathyroid hormone 1-34 enhances titanium implant anchorage in low-density trabecular bone: a correlative micro-computed tomographic and biomechanical analysis.

The use of endosseous titanium implants is the standard of care in dentistry and orthopaedic surgery. Nevertheless, implantation in low-density bone has a poor prognosis and experimental studies show delayed implant anchorage following gonadectomy-induced bone loss. Intermittently administered human parathyroid hormone 1-34 [iahPTH(1-34)] is the leading bone anabolic therapy. Hence, this study assessed whether iahPTH(1-34) enhances titanium implant integration in low-density bone. Threaded titanium implants, 0.9 mm in diameter, were inserted horizontally into the proximal tibial metaphysis of 5-month-old rats, 7 weeks postorchiectomy (ORX). Subcutaneous administration of iahPTH(1-34), at 5, 25 and 75 microg/kg/day commenced immediately thereafter and lasted for 8 weeks. Quantitative micro-computed tomography (muCT) at the implantation site was carried out at 15 microm resolution using high energy and long integration time to minimize artifacts resulting from the high implant radiopacity. Osseointegration (OI) was calculated as percent implant surface in contact with bone (%OI) quantified as the ratio of "bone"-to-total voxels in contact with the implant. Additionally, the trabecular bone volume density (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and connectivity density (Conn.D) were measured in the peri-implant bone. All microCT parameters were stimulated by iahPTH(1-34) dose-dependently; the percent maximal enhancement was %OI = 143, BV/TV = 257, Tb.Th = 150, Tb.N = 140 and Conn.D = 193. The maximal values of %OI, BV/TV and Tb.Th in iahPTH(1-34)-treated ORX rats exceeded significantly those measured in the implantation site of untreated sham-ORX controls. The same specimens were then subjected to pullout biomechanical testing. The biomechanical parameters were also enhanced by iahPTH(1-34) dose-dependently, exceeding the values recorded in the sham-ORX controls. The percent iahPTH(1-34)-induced maximal enhancement was: ultimate force = 315, stiffness = 270 and toughness = 395. Except for the BV/TV and Tb.Th, there was no significant difference between the effect of the 25 and 75 microg/kg/day doses. There was a highly significant correlation between the morphometric and biomechanical parameters suggesting the use of quantitative CT as predictive of the implant mechanical properties. These findings demonstrate that iahPTH(1-34) effectively stimulates implant anchorage in low-density trabecular bone and thus the feasibility of administering iahPTH(1-34) to improve the clinical prognosis in low-density trabecular bone sites.

Animals↗

PubMed2006

Importance of individual rods and plates in the assessment of bone quality and their contribution to bone stiffness.

UNLABELLED: Local morphometry based on the assessment of individual rods and plates was applied to 42 human vertebral trabecular bone samples. Results showed that multiple linear regression models based on local morphometry as a measure for bone microstructure helped improving our understanding of the role of local structural changes in the determination of bone stiffness as assessed from direct and computational biomechanics. INTRODUCTION: In a recent study, we proposed a method for local morphometry of trabecular bone, i.e., morphometry as applied to individual rods and plates. In this study, we used this method to study the relative importance of local morphometry in the assessment of bone architecture and its relative contribution to the stiffness of human vertebral bone. MATERIALS AND METHODS: We extracted 42 human trabecular bone autopsies from nine intact spinal columns. The cylindrical samples were imaged with muCT to assess bone microstructure. From these images, global and local morphometric indices were derived and related to Young's modulus as assessed by experimental uniaxial compression testing (Emeas) and computational finite element analysis (EFE). RESULTS: We found the best single predictor for Young's modulus to be apparent bone volume density (BV/TV), which explained 89% of the variance in EFE when fitted with a power law. A multiple linear regression model combining mean trabecular spacing (Tb.Sp), mean slenderness of the rods ( ), and the relative amount of rod volume to total bone volume (Ro.BV/BV) was able to explain 90% of the variance in EFE. This model could not be improved by adding BV/TV as an independent variable. Furthermore, we found that mean trabecular thickness of the rods was significantly related to EFE (r2 = 0.42), whereas mean trabecular thickness of plates had no correlation to Young's modulus. Because the globally determined trabecular thickness does not discriminate between rods and plates, this index had only a poor predictive power for EFE (r2 = 0.09), showing the importance of local analysis of individual rods and plates. CONCLUSIONS: From these results, we conclude that models based on local morphometry help improving our understanding of the relative importance of local structural changes in the determination of the stiffness of bone. Separate analysis of individual rods and plates may help to better predict age and disease-related fractures as well as to shed new light on the effect of pharmaceutical intervention in the prevention of such fractures beyond BMD.

Biomechanical Phenomena↗

PubMed2006

The influence of surface coatings of dicalcium phosphate (DCPD) and growth and differentiation factor-5 (GDF-5) on the stability of titanium implants in vivo.

Mechanical stability of implants is usually tested by pull out or push out tests which destroy the interface between the implant and bone. Pull out tests do not ideally reflect the clinical situation. In contrast, applying submaximal load leads to more physiologic micro-displacement between implant and bone. The aim of this study was to evaluate a new non-destructive mechanical testing device on different modifications of titanium implants. In 18 rabbits we investigated the influence of a dicalcium phosphate (DCPD) coating, or of a growth and differentiation factor-5 (GDF-5) coating, or a combination of both on the stability of titanium implants. The stability of implant was assessed by a non-destructive micro-measurement. In the same specimens the interface was investigated by micro-CT and histological evaluation. Surface modifications had a positive effect on the implant stability regarding displacement (p=0.001). Mechanical stability correlated with the quality of peri-implant tissue. Micro-displacement correlated negatively with the bone formation around the implants in histomorphometric evaluation (p=0.02). Amount of peri-prosthetic soft tissue showed a positive correlation with micro-displacement (p=0.01). Our findings indicate the positive effect of DCPD and GDF-5 coatings on stability of titanium implants. Results demonstrate the non-destructive testing to be an effective method to evaluate mechanical stability of implants.

Adhesiveness↗

PubMed2006

Local delivery of bisphosphonate from coated orthopedic implants increases implants mechanical stability in osteoporotic rats.

Patients with osteoporosis and joint disabilities represent a constant growing and challenging population to be treated in the musculoskeletal clinical field. Especially in the case of total hip arthroplasty, new solutions should be developed to compensate for the double negative factors, peri-implant osteolysis, and osteoporotic bone loss, affecting the quality of implant outcome. The goal of this study was then to establish a proof of concept for orthopedic implant used as Zoledronate delivery in osteoporotic rats, and in particular, to verify if this approach could increase the initial implant stability. Twenty-five female 6-month-old Wistar rats were ovariectomized 6 weeks before the implantation to induce osteoporosis. The animals were randomly separated in five groups representing the different Zoledronate concentrations in the HA coating: 0, 0.2, 2.1, 8.5, and 16 microg/implant. Histomorphometric measures and peri-implant bone volume fraction were assessed and mechanical stability tests were performed. Bone volume fraction and biomechanical results clearly illustrate the positive effect of Zoledronate coated implants in the osteoporotic rats. A remarkable result was to show the existence of a window of Zoledronate content (0.2 to 8.5 microg/implant) in which the mechanical fixation of the implant increased. We were able to establish the proof of concept for orthopedic implants used as a drug delivery system in osteoporotic rats. The local bisphosphonate delivery from a calcium phosphate coating allowed increase of the mechanical fixation of an orthopedic implant. This study shows that orthopedic implants containing bisphosphonates could be beneficial for osteoporotic patients in need of a total joint replacement.

Animals↗

PubMed2006

Heparanase is expressed in osteoblastic cells and stimulates bone formation and bone mass.

Heparan sulfate proteoglycans (HSPGs) are ubiquitous macromolecules. In bone, they are associated with cell surfaces and the extracellular matrix (ECM). The heparan sulfate (HS) chains of HSPGs bind a multitude of bioactive molecules, thereby controlling normal and pathologic processes. The HS-degrading endoglycosidase, heparanase, has been implicated in processes such as inflammation, vascularization associated with wound healing and malignancies, and cancer metastasis. Here we show progressive mRNA expression of the hpa gene (encoding heparanase) in murine bone marrow stromal cells undergoing osteoblastic (bone forming) differentiation and in primary calvarial osteoblasts. Bone marrow stromal cells derived from transgenic mice expressing recombinant human heparanase (rh-heparanase) and MC3T3 E1 osteoblastic cells exposed to soluble rh-heparanase spontaneously undergo osteogenic differentiation. In addition, the transgenic bone marrow stromal cells degrade HS chains. In wild-type (WT) and hpa-transgenic (hpa-tg) mice, heparanase is weakly expressed throughout the bone marrow with a substantial increase in osteoblasts and osteocytes, especially in the hpa-tg mice. Heparanase expression was absent in osteoclasts. Micro-computed tomographic and histomorphometric skeletal analyses in male and female hpa-tg versus WT mice show markedly increased trabecular bone mass, cortical thickness, and bone formation rate, but no difference in osteoclast number. Collectively, our data suggest that proteoglycans tonically suppress osteoblast function and that this inhibition is alleviated by HS degradation with heparanase.

Animals↗

PubMed2006

Trabecular bone failure at the microstructural level.

Although biomedical imaging technology is now readily available, few attempts have been made to expand the capabilities of these systems by adding not only quantitative but also functional analysis tools combining microimaging with time-lapsed mechanical testing. An area of special interest is multiscale functional imaging of trabecular bone to assess the relative importance of bone "quality" in the assessment of the mechanical competence of bone. First, relevant studies dealing with hierarchical imaging of trabecular bone and classic analyses such as quantitative morphometry and finite-element analysis to predict bone strength are reviewed. Second, studies are presented investigating failure mechanisms of three-dimensional trabecular bone through dynamic, time-lapsed microimaging, including image-guided techniques developed for this purpose and utilizing microcompression. For the first time, these allow the direct three-dimensional visualization and quantification of failure initiation and progression at the microstructural level.

Biomechanical Phenomena↗

PubMed2006

Smooth surface meshing for automated finite element model generation from 3D image data.

Finite element (FE) modelling based on data from three-dimensional high-resolution computed tomography (CT) imaging systems provides a non-invasive method to assess structural mechanics. Automated mesh generation from these voxel based image data can be achieved by direct conversion to hexahedron elements, however these model representations have jagged edges. This paper proposes an automated method to generate smoothed FE meshes from voxel-based image data. Mesh fairing processes are utilized that allow constraints that control the smoothing process, and are computationally efficient. Surfaces of the mesh on the exterior, as well as interfaces between two tissues, can be smoothed by varying fairing parameters and constraint criteria. The method was tested on a variety of real and simulated three-dimensional data sets, resulting in both hexahedron and tetrahedron meshes. It was shown that the fairing process is linearly related to the number of smoothing iterations, and that peak stresses are reduced in FE simulations of the smoothed models. Although developed for micro-CT data sets, this fast and reliable mesh smoothing method could be applied to any three-dimensional image data where node and element connectivity have been defined.

Animals↗

PubMed2006

Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II: biofunctional characteristics.

We present here the biological performance in supporting tissue regeneration of hybrid hydrogels consisting of genetically engineered protein polymers that carry specific features of the natural extracellular matrix, cross-linked with reactive poly(ethylene glycol) (PEG). Specifically, the protein polymers contain the cell adhesion motif RGD, which mediates integrin receptor binding, and degradation sites for plasmin and matrix-metalloproteinases, both being proteases implicated in natural matrix remodeling. Biochemical assays as well as in vitro cell culture experiments confirmed the ability of these protein-PEG hydrogels to promote specific cellular adhesion and to exhibit degradability by the target enzymes. Cell culture experiments demonstrated that proteolytic sensitivity and suitable mechanical properties were critical for three-dimensional cell migration inside these synthetic matrixes. In vivo, protein-PEG matrixes were tested as a carrier of bone morphogenetic protein (rhBMP-2) to heal critical-sized defects in a rat calvarial defect model. The results underscore the importance of fine-tuning material properties of provisional therapeutic matrixes to induce cellular responses conducive to tissue repair. In particular, a lack of rhBMP or insufficient degradability of the protein-PEG matrix prevented healing of bone defects or remodeling and replacement of the artificial matrix. This work confirms the feasibility of attaining desired biological responses in vivo by engineering material properties through the design of single components at the molecular level. The combination of polymer science and recombinant DNA technology emerges as a powerful tool for the development of novel biomaterials.

Amino Acid Sequence↗

PubMed2005

Volumetric spatial decomposition of trabecular bone into rods and plates--a new method for local bone morphometry.

Bone microarchitecture is believed to play a key role in determining bone quality. We therefore present a new method for the volumetric spatial decomposition of trabecular bone samples into its basic elements (rods and plates). This new method is a framework for the element based description of bone microarchitecture. First, the newly developed algorithm was validated on computer-generated models. Then, it was applied to 328 human trabecular bone samples harvested from 70 donors at five different anatomical sites (calcaneus, femoral head, iliac crest, lumbar spine 2 and 4), which were previously scanned by microcomputed tomography. Standard three-dimensional morphometric algorithms were used to analyze the trabeculae on an individual basis with respect to their volume, surface, and thickness. The results were statistically compared for the five sites. In this study, it was possible for the first time to spatially decompose trabecular bone structures in its volumetric elements; rods and plates. The size of the largest element in the structures showed significant differences for the five compared sites. In samples from femoral head, we found that basically one "major element" was spanning through the whole structure whereas in lumbar spine and calcaneus, smaller elements dominate. From this, we suggest that the strength of strong, dense plate-like structures is determined by the major elements whereas in looser rod-like structures the strength is given by the arrangement, quality, and shape of a whole set of elements. Furthermore, we found that globally determined structural indices such as the mean curvature of the bone surface ( ) or related to this the structure model index (SMI) are almost exclusively explained by the arrangement of the plates. This also suggests that rods hold independent information characterizing trabecular bone quality, especially in the spine. These findings may improve the understanding of the site-specific role of bone microarchitecture in determining bone quality and in future studies the competence of bone.

Adult↗

PubMed2005

Architecture and properties of anisotropic polymer composite scaffolds for bone tissue engineering.

Bone is a complex porous composite structure with specific characteristics such as viscoelasticity and anisotropy, both in morphology and mechanical properties. Bone defects are regularly filled with artificial tissue grafts, which should ideally have properties similar to those of natural bone. Open cell composite foams made of bioresorbable poly(L-lactic acid) (PLA) and ceramic fillers, hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP), were processed by supercritical CO2 foaming. Their internal 3D-structure was then analysed by micro-computed tomography (microCT), which evidenced anisotropy in morphology with pores oriented in the foaming direction. Furthermore compressive tests demonstrated anisotropy in mechanical behaviour, with an axial modulus up to 1.5 times greater than the transverse modulus. Composite scaffolds also showed viscoelastic behaviour with increased modulus for higher strain rates. Such scaffolds prepared by gas foaming of polymer composite materials therefore possess suitable architecture and properties for bone tissue engineering applications.

Anisotropy↗

PubMed2005

Testing two predictions for fracture load using computer models of trabecular bone.

Aging induces several types of architectural changes in trabecular bone including thinning, increased levels of anisotropy, and perforation. It has been determined, on the basis of analysis of mathematical models, that reduction in fracture load caused by perforation is significantly higher than those due to equivalent levels of thinning or anisotropy. The analysis has also provided an expression which relates the fractional reduction of strength tau to the fraction of elements nu that have been removed from a network. Further, it was proposed that the ratio Gamma of the elastic constant of a sample and its linear response at resonance can be used as a surrogate for tau. Experimental validation of these predictions requires following architectural changes in a given sample of trabecular bone; techniques to study such changes using microcomputed tomography are only beginning to be available. In the present study, we use anatomically accurate computer models constructed from digitized images of bone samples for the purpose. Images of healthy bone are subjected to successive levels of synthetic degradation via surface erosion. Computer models constructed from these images are used to calculate their fracture load and other mechanical properties. Results from these computations are shown to be consistent with predictions derived from the analysis of mathematical models. Although the form of tau(nu) is known, parameters in the expression are expected to be sample-specific, and hence nu is not a reliable predictor of strength. We provide an example to demonstrate this. In contrast, analysis of model networks shows that the linear part of tau(Gamma) depends only on the structure of trabecular bone. Computations on models constructed from samples of iliac crest trabecular bone are shown to be in agreement with this assertion. Since Gamma can be computed from a vibrational assessment of bone, we argue that the latter can be used to introduce new surrogates for bone strength and hence diagnostic tools for osteoporosis.

Bone Density↗