Trabecular Bone Tissue Research Articles

The Control of Mesenchymal Stromal Cell Osteogenic Differentiation through Modified Surfaces

Stem cells continue to receive widespread attention due to their potential to revolutionise treatments in the fields of both tissue engineering and regenerative medicine. Adult stem cells, specifically mesenchymal stromal cells (MSCs), play a vital role in the natural events surrounding bone healing and osseointegration through being stimulated to differentiate along their osteogenic lineage and in doing so, they form new cortical and trabecular bone tissue. Understanding how to control, manipulate, and enhance the intrinsic healing events modulated through osteogenic differentiation of MSCs by the use of modified surfaces and biomaterials could potentially advance the fields of both orthopaedics and dentistry. This could be by either using surface modification to generate greater implant stability and more rapid healing following implantation or the stimulation of MSCs ex vivo for reimplantation. This review aims to gather publications targeted at promoting, enhancing, and controlling the osteogenic differentiation of MSCs through biomaterials, nanotopographies, and modified surfaces for use in implant procedures.

The Importance of Intrinsic Damage Properties to Bone Fragility: A Finite Element Study

As the average age of the population has increased, the incidence of age-related bone fracture has also increased. While some of the increase of fracture incidence with age is related to loss of bone mass, a significant part of the risk is unexplained and may be caused by changes in intrinsic material properties of the hard tissue. This investigation focused on understanding how changes to the intrinsic damage properties affect bone fragility. We hypothesized that the intrinsic (μm) damage properties of bone tissue strongly and nonlinearly affect mechanical behavior at the apparent (whole tissue, cm) level. The importance of intrinsic properties on the apparent level behavior of trabecular bone tissue was investigated using voxel based finite element analysis. Trabecular bone cores from human T12 vertebrae were scanned using microcomputed tomography (μCT) and the images used to build nonlinear finite element models. Isotropic and initially homogenous material properties were used for all elements. The elastic modulus (E(i)) of individual elements was reduced with a secant damage rule relating only principal tensile tissue strain to modulus damage. Apparent level resistance to fracture as a function of changes in the intrinsic damage properties was measured using the mechanical energy to failure per unit volume (apparent toughness modulus, W(a)) and the apparent yield strength (σ(ay), calculated using the 0.2% offset). Intrinsic damage properties had a profound nonlinear effect on the apparent tissue level mechanical response. Intrinsic level failure occurs prior to apparent yield strength (σ(ay)). Apparent yield strength (σ(ay)) and toughness vary strongly (1200% and 400%, respectively) with relatively small changes in the intrinsic damage behavior. The range of apparent maximum stresses predicted by the models was consistent with those measured experimentally for these trabecular bone cores from the experimental axial compressive loading (experimental: σ(max) = 3.0-4.3 MPa; modeling: σ(max) = 2-16 MPa). This finding differs significantly from previous studies based on nondamaging intrinsic material models. Further observations were that this intrinsic damage model reproduced important experimental apparent level behaviors including softening after peak load, microdamage accumulation before apparent yield (0.2% offset), unload softening, and sensitivity of the apparent level mechanical properties to variability of the intrinsic properties.

Novel method to analyze post-yield mechanical properties at trabecular bone tissue level

Tissue level mechanics is a key factor to be investigated to improve the knowledge of how the overall trabecular structure reacts to loading and overloading. The aim of this study was to develop a new device for measuring the mechanical competence of single trabeculae in the post-yield region for both tensile and bending tests, characterized by high accuracy and precision, and to assess the effect of testing mode, donor age and material composition. A novel approach for measuring the displacement and deformation was developed (accuracy error of 0.3% and a precision of 2.7%). A total of 30 samples from two bovine femora of different ages (from <3-year-old and 14-year-old cows) were tested in tension or bending, while average material properties have been acquired by means of Raman spectroscopy. A group of trabeculae was tested in bending after treatment for collagen degradation. As a result, a complete set of post-yield properties has been reported. The results highlight significant differences between tensile and bending groups, with higher values for the bending test mode for yield strain, ultimate strain and post-yield work and lower for the elastic modulus. Significant higher values were found for the old donor (differences in the range of 30–60%) for elastic modulus, yield stress and ultimate stress as well as for material properties measured by Raman spectroscopy. We quantified that changes in materials properties induced by collagen degradation corresponded to a substantial decrease (up to 120% for post-yield work) of mechanical competence, both in the elastic and inelastic region.

Computational Modeling of Interaction of Dental Implant with Mandible

This paper is focused on computational modeling of an interaction of dental implant with mandible bone. It describes creation of computational model including model of geometry, materials, loads and constraints. There is a comparative stress-strain analysis of the levels of cancellous bone model. Computations are performed with the use of finite element method. Results show differences between the model which includes trabecular architecture of cancellous bone tissue and the model with non-trabecular cancellous bone tissue. For better description of the processes in bone tissue and at the interface between bone tissue and implant, it is necessary to create the computational model on the highest possible level, i.e. with the trabecular bone tissue.

Human bone hardness seems to depend on tissue type but not on anatomical site in the long bones of an old subject

It has been hypothesised that among different human subjects, the bone tissue quality varies as a function of the bone segment morphology. The aim of this study was to assess and compare the quality, evaluated in terms of hardness of packages of lamellae, of cortical and trabecular bones, at different anatomical sites within the human skeleton. The contralateral six long bones of an old human subject were indented at different levels along the diaphysis and at both epiphyses of each bone. Hardness value, which is correlated to the degree of mineralisation, of both cortical and trabecular bone tissues was calculated for each indentation location. It was found that the cortical bone tissue was harder (+18%) than the trabecular one. In general, the bone hardness was found to be locally highly heterogeneous. In fact, considering one single slice obtained for a bone segment, the coefficient of variation of the hardness values was up to 12% for cortical bone and up to 17% for trabecular bone. However, the tissue hardness was on average quite homogeneous within and among the long bones of the studied donor, although differences up to 9% among levels and up to 7% among bone segments were found. These findings seem not to support the mentioned hypothesis, at least not for the long bones of an old subject.

Computerized quantification of bone tissue and marrow in stained microscopic images

Stained histological images assist physicians to identify different types of tissues or cells and their architectures. They can be applied on the diagnosis of various diseases and the assessment of treatment effects. Osteoporosis is an aging disease that reduces the density of bones and increases the risk of bone fracture. Literatures indicate that osteoporosis is associated with the ratio of trabecular bone tissues and bone marrow cells, and bones in osteoporosis patients consist of a significantly higher marrow fat content. Interactive segmentation of bone tissue and different types of bone marrow cells in high-resolution histological images, however, is a very tedious and labor-intensive process. The aim of this study is to develop an automatic algorithm to quantify the areas of different tissues such as the trabecular bones and yellow and red marrow cells. This image segmentation method consists of a series of mathematical morphological operation steps based on both the color and morphology features of tissues and was implemented in Matlab. The results obtained from the proposed method have been verified by comparing with those obtained interactively from an experienced histotechnician (Pearson correlation coefficient > 0.94, P < 0.001). The result suggests that the proposed algorithm can effectively assist physicians to quantify stained bone histological images.

Numerical simulation of the remodelling process of trabecular architecture around dental implants

Dental implants may alter the mechanical environment in the jawbone, thereby causing remodelling and adaptation of the surrounding trabecular bone tissues. To improve the efficacy of dental implant systems, it is necessary to consider the effect of bone remodelling on the performance of the prosthetic systems. In this study, finite element simulations were implemented to predict the evolution of microarchitecture around four implant systems using a previously developed model that combines both adaptive and microdamage-based mechano-sensory mechanisms in bone remodelling process. Changes in the trabecular architecture around dental implants were mainly focused. The simulation results indicate that the orientational and ladder-like architecture around the implants predicted herein is in good agreement with those observed in animal experiments and clinical observations. The proposed algorithms were shown to be effective in simulating the remodelling process of trabecular architecture around dental implant systems. In addition, the architectural features around four typical dental implant systems in alveolar bone were evaluated comparatively.

TCDD-induced modulation of cortical and trabecular bone tissue is dependent on the aryl hydrocarbon receptor

TCDD-induced modulation of cortical and trabecular bone tissue is dependent on the aryl hydrocarbon receptor

Relating micromechanical properties and mineral densities in severely suppressed bone turnover patients, osteoporotic patients, and normal subjects

Mineralization of bone, from the tissue level to whole bones, is associated with mechanical properties. The relationship between bone tissue mineralization and micromechanical properties may be affected by age, disease, and drug treatment. Patients with severely suppressed bone turnover (SSBT) suffered atypical fractures while on bisphosphonate treatment. The role of tissue level mineralization in predicting material level properties of SSBT bone may be different from that of other osteoporotic patients and of normal subjects. The aim of this study was to compare the relationships between mineralization and micromechanical properties of bone biopsies from patients with SSBT, bisphosphonate-naive osteoporotic patients with typical vertebral fracture, and normal young and age-matched subjects. We used nanoindentation and quantitative backscattered electron microscopy to characterize the elastic modulus, contact hardness, plastic deformation resistance, and tissue mineralization of the biopsies at site-matched locations within each biopsy. The linear mineralization–mechanical property relationships were different among the groups with respect to the intercepts for only cortical bone tissue but not the slopes for cortical and trabecular bone tissues. For a given mineral density, there was a trend of greater plastic deformation resistance in SSBT cortical bone compared to young normal bone. Similarly, there was a trend of greater plastic deformation resistance in osteoporotic trabecular bone compared to young normal bone for a given mineral density. The age-matched normal group had higher elastic modulus and a trend of higher contact hardness compared to the young normal group for a given mineral density. However, the mechanical property–mineralization relationships within an individual were weak, and only 21 of 53 biopsies that were analyzed had at least one significant association between mineralization and a mechanical property measurement for either cortical or trabecular bone tissues. The average properties of microstructural regions (deep and superficial remodeling packets in trabecular bone; osteonal and interstitial regions in cortical bone) were consistent with mineral accumulation with tissue age, with the exception of the SSBT group. SSBT trabecular bone deep packets had higher hardness and plastic deformation resistance than superficial packets, but mineralization levels and tissue modulus were not different between packet types. We conclude that relationships between mineral and mechanical properties were different between fracture and normal groups and between young and old normal groups, and that atypical fracture may be associated with changed microstructural material properties and tissue level mineralization compared to osteoporotic patients with vertebral fracture and normal subjects. We hypothesize that tissue level bone quality may be an important determinant in fracture risk, such that tissue mineral density may predict different material properties in different patient groups.

Failure modelling of trabecular bone using a non-linear combined damage and fracture voxel finite element approach

Trabecular bone tissue failure can be considered as consisting of two stages: damage and fracture; however, most failure analyses of 3D high-resolution trabecular bone samples are confined to damage mechanisms only, that is, without fracture. This study aims to develop a computational model of trabecular bone consisting of an explicit representation of complete failure, incorporating damage criteria, fracture criteria, cohesive forces, asymmetry and large deformation capabilities. Following parameter studies on a test specimen, and experimental testing of bone sample to complete failure, the asymmetric critical tissue damage and fracture strains of ovine vertebral trabecular bone were calibrated and validated to be compression damage -1.16 %, tension damage 0.69 %, compression fracture -2.91 % and tension fracture 1.98 %. Ultimate strength and post-ultimate strength softening were captured by the computational model, and the failure of individual struts in bending and shear was also predicted. This modelling approach incorporated a cohesive parameter that provided a facility to calibrate ductile-brittle behaviour of bone tissue in this non-linear geometric and non-linear constitutive property analyses tool. Finally, the full accumulation of tissue damage and tissue fracture has been monitored from range of small magnitude (normal daily loading) through to specimen yielding, ultimate strength and post-ultimate strength softening.

Ultrasound propagation in trabecular bone: a numerical study of the influence of micro-cracks

The accumulation of microdamage in trabecular bone tissue is suspected of being a predictive indicator of osteoporosis diagnosis. To quantify this microdamage, the Dynamic AcoustoElastic Testing (DAET) method measures the time of flight (TOF) and amplitude variations of transmitted ultrasound (US) pulses, while the bone sample is submitted to a low frequency pressure (opening/closing of microcracks). However, DAET is both sensitive to viscoelastic properties changes and microcracks density. To estimate the microcraks density contribution, a numerical approach is proposed, allowing simulations of different levels of microdamaged media. A 2D pseudo-spectral time domain numerical model was then developed to simulate linear wave propagation in heterogeneous solids including thermo-viscous attenuation. The influence of the microcracks number, size and orientation on the US TOF and amplitude was particularly investigated. Results are discussed and compared with experimental data extracted from DAET measurements in trabecular bone samples.

Analytical model of Dynamic AcoustoElastic Testing measurements in trabecular bone tissue: a rheological approach

A dynamic acoustoelastic testing (DAET) method based on the interaction of two acoustical waves was developed to measure viscoelastic properties of trabecular bone tissue. While a sinusoidal low-frequency (LF) acoustic wave successively compresses and expands the medium, ultrasonic (US) pulses are generated to probe the uniformly stressed medium (quasi-static pressure, pLF). The US pulses velocity and amplitude (c, A) vary with respect to the medium stress level. These modulations (c(pLF)-c(0); A(pLF)-A(0)) are plotted as a function of the instantaneous LF pressure. From these rheograms, nonlinear elastic and viscous (dissipative) parameters, β' and β” respectively, are extracted. Since the US velocity is directly related to the medium viscoelastic modulus (M*), considering either the celerity variations or the modulus variations as a function of LF pressure is equivalent. In this perspective, we developed an analytical model of the variations of M*, derived from the Kelvin-Voigt approach (M* as a functio...

Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1-84): A randomized controlled study

Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high bone mineral density (BMD) despite conventional treatment with calcium supplements and active vitamin D analogues. To assess effects of PTH substitution therapy on 3-dimensional bone structure, we randomized 62 patients with hypoPT into 24 weeks of treatment with either PTH(1-84) 100 µg/day subcutaneously or similar placebo as an add-on therapy. Micro-computed tomography was performed on 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24 weeks of treatment. Compared with placebo, PTH caused a 27% lower trabecular thickness (p < 0.01) and 4% lower trabecular bone tissue density (p < 0.01), whereas connectivity density was 34% higher (p < 0.05). Trabecular tunneling was evident in 11 (48%) of the biopsies from the PTH group. Patients with tunneling had significantly higher levels of biochemical markers of bone resorption and formation. At cortical bone, number of Haversian canals per area was 139% higher (p = 0.01) in the PTH group, causing a tendency toward an increased cortical porosity (p = 0.09). At different subregions of the hip, areal BMD (aBMD) and volumetric BMD (vBMD), as assessed by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), decreased significantly by 1% to 4% in the PTH group. However, at the lumbar spine, aBMD decreased by 1.8% (p < 0.05), whereas vBMD increased by 12.8% (p = 0.02) in the PTH compared with the placebo group.

Bone tissue composition varies across anatomic sites in the proximal femur and the iliac crest

The extent to which bone tissue composition varies across anatomic sites in normal or pathologic tissue is largely unknown, although pathologic changes in bone tissue composition are typically assumed to occur throughout the skeleton. Our objective was to compare the composition of normal cortical and trabecular bone tissue across multiple anatomic sites. The composition of cadaveric bone tissue from three anatomic sites was analyzed using Fourier transform infrared imaging: iliac crest (IC), greater trochanter (GT), and subtrochanteric femur (ST). The mean mineral:matrix ratio was 20% greater in the subtrochanteric cortex than in the cortices of the iliac crest (p = 0.004) and the greater trochanter (p = 0.02). There were also trends toward 30% narrower crystallinity distributions in the subtrochanteric cortex than in the greater trochanter (p = 0.10) and 30% wider crystallinity distributions in the subtrochanteric trabeculae than in the greater trochanter (p = 0.054) and the iliac crest (p = 0.11). Thus, the average cortical tissue mineral content and the widths of the distributions of cortical crystal size/perfection differ at the subtrochanteric femur relative to the greater trochanter and the iliac crest. In particular, the cortex of the iliac crest has lower mineral content relative to that of the subtrochanteric femur and may have limited utility as a surrogate for subtrochanteric bone.

Multiple quantitative trait loci for cortical and trabecular bone regulation map to mid-distal mouse chromosome 4 that shares linkage homology to human chromosome 1p36

The mid-distal region of mouse chromosome 4 (Chr 4) is homologous with human Chr 1p36. Previously, we reported that mouse Chr 4 carries a quantitative trait locus (QTL) with strong regulatory effect on volumetric bone mineral density (vBMD). The intent of this study is to utilize nested congenic strains to decompose the genetic complexity of this gene-rich region. Adult females and males from 18 nested congenic strains carrying discrete C3H sequences were phenotyped for femoral mineral and volume by pQCT and for trabecular bone volume (BV), tissue volume (TV), trabecular number (Trab.no), and trabecular thickness (Trab.thk) by MicroCT 40. Our data show that the mouse Chr 4 region consists of at least 10 regulatory QTL regions that affected either or both pQCT and MicroCT 40 phenotypes. The pQCT phenotypes were typically similar between sexes, whereas the MicroCT 40 phenotypes were divergent. Individual congenic strains contained one to seven QTL regions. These regions conferred large positive or negative effects in some congenic strains, depending on the particular bone phenotype. The QTL regions II to X are syntenic with human 1p36, containing from 1 to 102 known genes. We identified 13 candidate genes that can be linked to bone within these regions. Six of these genes were linked to osteoblasts, three linked to osteoclasts, and two linked to skeletal development. Three of these genes have been identified in Genome Wide Association Studies (GWAS) linked to 1p36. In region III, there is only one gene, Lck, which conferred negative pQCT and MicroCT 40 phenotypes in both sexes. This gene is important to development and functioning of T cells, has been associated with osteoclast activity, and represents a novel bone regulatory gene that merits further experimental evaluation. In summary, congenic strains are powerful tools for identifying regulatory regions that influence bone biology and offer models for testing hypotheses about gene-gene and gene-environment interactions that are not available to experimental work in humans.

Influence of creatine supplementation on bone quality in the ovariectomized rat model: an FT-Raman spectroscopy study

The influence of creatine (Cr) supplementation on cortical and trabecular bone from ovariectomized rats was studied using FT-Raman spectroscopy. The intensity of organic-phase Raman bands was compared to mineral phase ones. Twenty-one female Wistar rats aged 3 months were divided into three groups (n = 7 per group): ovariectomized (OVX), ovariectomized treated with creatine (CRE) and sham-operated (SHAM) groups. Creatine supplementation (300 mg kg(-1) day(-1)) was provided for 8 weeks, starting 12 weeks after ovariectomy. FT-Raman spectroscopy was performed on the right medial femoral mid-shaft (cortical bone) and third lumbar vertebral body (trabecular bone). The integrated intensities of mineral phase (phosphate and carbonate bands at 959 and 1,071 cm(-1), respectively) and organic phase (amide I band at 1,665 cm(-1)) Raman bands were analyzed. The mineral-to-matrix (phosphate/amide I), carbonate-to-phosphate, and carbonate-to-amide I ratios were analyzed to assess bone quality. The phosphate content on trabecular bone was higher in the CRE group than the OVX group (p < 0.05). No significant changes in mineral or organic phases on cortical bone were observed. A radiographic assessment of bone density was encouraging as the same findings were showed by Raman intensity of phosphate from cortical (r(2) = 0.8037) and trabecular bones (r(2) = 0.915). Severe ovariectomy-induced bone loss was confirmed by FT-Raman spectroscopy. The results suggest that the chemical composition of trabecular bone tissue may be positively influenced by Cr supplementation after ovariectomy.

Trabecular bone adaptation in a finite element frame model using load dependent fabric tensors

Most human bones are divided into an external cortical and an internal trabecular substance. Both kinds of bone tissue are capable of adapting their strength to the loads acting upon them; they are in a state of continuous remodelling. The present study introduces a new method for modelling the functional adaptation of the trabecular bone by means of a finite element frame model, where each trabecula is represented by one beam element in order to achieve a relatively simple model with a low element number. The model is generated in a stochastic way, thus avoiding the need for CT imaging. For the purpose of the remodelling simulations a structure consisting of two kinds of beam elements is used. The elements involved in carrying loads are called ‘active’ beams, while those not working are regarded as ‘passive’ beams. Any modification in the structure is executed by changing the active elements into passive or vice versa according to the eigenvalues of node-by-node defined fabric tensors. The algorithm generates anisotropic structures, with load-directed beam orientations similar to the living trabecular bone tissue.

Histomorphometric analysis of bone marrow constituents in ovariectomized Cimicifuga racemosa (L.) Nutt. (CR) treated animals

Following ovariectomy (ovx) rats lose trabecular bone and hematopoietic tissue whereas the amount of fat tissue increases. These fat cells secrete cytotoxic cytokines which cause local inflammation in the bone marrow which augments development of osteoporosis. Whether this can be prevented by estradiol-17ß (E2) or CR BNO 1055 was tested.

Relationship of sclerostin and secreted frizzled protein polymorphisms with bone mineral density

Secreted frizzled-related protein and sclerostin, encoded by FRZB and SOST genes, respectively, are extracellular Wnt inhibitors that tend to decrease bone formation. The purpose of this study was to explore the association of the sets of polymorphisms capturing common variations of these genes with bone mineral density (BMD). Twelve polymorphic loci of the FRZB gene and 7 of the SOST gene were genotyped in postmenopausal women from two Spanish regions (Cantabria, n = 1043, and Valencia, n = 342). The polymorphisms included tagging single nucleotide polymorphisms and single nucleotide polymorphisms with possible functional consequences assessed in silico. The rs4666865 polymorphism of the FRZB gene was associated with spine BMD in the Cantabria cohort in the single-locus (P = 0.008) and the haplotypic analysis. However, the results were not replicated in the Valencia cohort. Several polymorphisms at the 5' region of the SOST gene and, particularly, rs851056 were associated with BMD in women from both cohorts (P = 0.002 in Cantabria and P = 0.005 in Valencia). When the results of both cohorts were combined, the mean (SD) BMD difference across rs851056 genotypes was 47 (0.31) mg/cm(2) (P < 0.001). No differences in FRZB and SOST expression in femoral trabecular bone tissue were detected across genotypes. Polymorphisms in the 5' region of SOST gene are associated with BMD in postmenopausal women. They may contribute to explain, in part, the hereditary influence on bone mass.

Similar damage initiation but different failure behavior in trabecular and cortical bone tissue

The mechanical properties of bone tissue are reflected in its micro- and nanostructure as well as in its composition. Numerous studies have compared the elastic mechanical properties of cortical and trabecular bone tissue and concluded that cortical bone tissue is stiffer than trabecular bone tissue. This study compared the progression of microdamage leading to fracture and the related local strains during this process in trabecular and cortical bone tissue. Unmachined single bovine trabeculae and similarly-sized cortical bovine bone samples were mechanically tested in three-point bending and concomitantly imaged to assess local strains using a digital image correlation technique. The bone whitening effect was used to detect microdamage formation and propagation. This study found that cortical bone tissue exhibits significantly lower maximum strains (trabecular 36.6%±14% vs. cortical 22.9%±7.4%) and less accumulated damage (trabecular 16100±8800 pix/mm2 vs. cortical 8000±3400 pix/mm2) at failure. However, no difference was detected for the maximum local strain at whitening onset (trabecular 5.8%±2.6% vs. cortical 7.2%±3.1%). The differences in elastic modulus and mineral distribution in the two tissues were investigated, using nanoindentation and micro-Raman imaging, to explain the different mechanical properties found. While cortical bone was found to be overall stiffer and more highly mineralized, no apparent differences were noted in the distribution of modulus values or mineral density along the specimen diameter. Therefore, differences in the mechanical behavior of trabecular and cortical bone tissue are likely to be in large part due to microstructural (i.e. orientation and distribution of cement lines) and collagen related compositional differences.