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Cement lines are boundaries between secondary osteons and the surrounding interstitial bone tissue in cortical bone as well as between trabecular packets in trabecular bone tissue. The interfacial properties of cement lines have been determined by performing an osteon pushout test [1]. It supported the hypothesis that the cement line is a weak interface.

The biological response of bone cells (osteoblasts and/or osteocytes) to mechanical loading is an important basic science topic in the mechanism of mechano-signal transduction in bone adaptation to mechanical loading. The characterization of this mechanism of signal transduction is crucial in the understanding of the etiology of age-related bone loss, bone loss during space flight and the optimal design of implants for total joint replacements. It has been hypothesized that deformation-generated fluid shear stress is one of the major mechanical stimuli that bone cells respond to. Many in vitro experiments utilize a parallel-plate flow chamber by imposing fluid shear stress on cultured osteoblasts. For example, changes in intracellular Ca++ levels and mitogen-activated protein kinase (MAPK) phosphorylation has been quantified in response to applied shear flow [1,2]. In these studies, the flow shear stress at the wall of the flow chamber τ wall = 6 μ Q w h 2 , where Q is the volumetric flow rate, w and h are the width and height of the flow chamber, respectively, and μ is the media viscosity. However, this wall shear stress may not indicate the actual stress state which bone cells experience, which depends on the details of the flow-cell interaction, including the mechanical properties of the cell, the attachment condition of the cell to the wall as well as the cell density. In order to obtain a quantitative relationship between the biological response of bone cells to applied shear flow, it is necessary to quantify in detail the flow-cell interaction in a typical shear flow experiment. The objective of this study was to quantify the shear stress within the cell under applied shear flow, incorporating fully coupled flow and solid deformation analyses using the finite element technique. Specifically, we examined the influence of the elastic modulus of the cell and the spacing distance between cells on the shear stress within the cell.

Age-related bone fractures are mostly influenced by trabecular bone sites. Trabecular bone constantly adapts its bone volume fraction (BV/TV) and orientation, and thus its mechanical properties, to mechanical usage. Therefore, understanding the trabecular bone adaptation process and its consequences will contribute to the better understanding of the etiology of age-related fractures. Micro-computed tomography (micro-CT) is a relatively new method to quantify the complex three-dimensional (3D) trabecular bone architecture [1,2]. Finite element computational studies can be performed on these 3D microstructural images by converting each image voxel into an element [3,4,5]. Image thresholding techniques to segment bone voxels from bone marrow voxels have a major impact on the results of these models. However, the influence of different types of thresholding techniques on the mechanical properties of bone has not been examined carefully.

Age related changes in porosity of cortical bone have been previously reported. The cortical porosity increases with age in both men and women, from 4.6% in men and 4% in women at age 40 to 10% and more at age 80 (Laval-Jeantet et al., 1983). The porosity is defined as the percentage of cortical bone occupied by vascular and resorption cavities. There are a few quantitative data regarding the influences of Haversian canal and resorption space on porosity. Age related increases in Haversian canal size and Haversian canal number contribute to the increasing porosity of cortical bone for the elderly men and women (Thompson, 1980; Nyssen-behets et al., 1997). The number of osteoclastic resorption space is also greater in the old men than in the young men (Nyssen-Behets et al., 1997).

The role of mechanical loading in trabecular bone adaptation is important for the understanding of bone integrity in different loading scenarios such as microgravity and for the etiology of age-related bone fractures. There have been numerous in vivo animal studies of bone adaptation, most of which are related to cortical bone remodeling, aimed at the investigation of Wolff’s Law [4], An interesting experimental model for trabecular bone adaptation has been developed in the rat tail vertebrae [2,3]. This model is attractive for trabecular bone adaptation studies because a controlled mechanical load can be applied to a whole vertebra with minimal surgical trauma, using a relatively inexpensive animal model. In addition, with advanced micro computed tomography (micro-CT) or micro magnetic resonance imaging (micro-MRI) coupled with large scale finite element modeling techniques, it is possible to characterize the three-dimensional (3D) stress/strain environment in the bone tissue close to a cellular level (∼25μm) [1]. Therefore, this in vivo rat tail model has a tremendous potential for quantification of the relationship between mechanical stimulation and biological response in trabecular bone adaptation.

The mechanical properties of bone tissue are determined by composition as well as structural, microstructural and nanostructural organization. The aim of this study was to quantify the elastic properties of bone at the lamellar level and compare these properties among osteonal, interstitial and trabecular microstructures from the diaphysis and the neck of the human femur. A nanoindentation technique with a custom irrigation system was used for simultaneously measuring force and displacement of a diamond tip pressed 500 nm into the moist bone tissue. An isotropic elastic modulus was calculated from the unloading curve with an assumed Poisson ratio of 0.3, while hardness was defined as the maximal force divided by the corresponding contact area. The elastic moduli ranged from 6.9 +/- 4.3 GPa in trabecular tissue from the femoral neck of a 74 yr old female up to 25.0 +/- 4.3 GPa in interstitial tissue from the diaphyseal cortex of a 69 yr old female. The mean elastic modulus was found to be significantly influenced by the type of lamella (p < 10(-6)) and by donor (p < 10(-6)). The interaction between the type of lamella and the donor was also highly significant (p < 10(-6)). Hardness followed a similar distribution as elastic modulus among types of lamellae and donor, but with lower statistical contrast. It is concluded that the nanostructure of bone tissue must differ substantially among lamellar types, anatomical sites and individuals and suggests that tissue heterogeneity is of potential importance in bone fragility and adaptation.

Morphologically, cortical bone resembles a fiber-matrix composite material such that an osteon is analogous to the fiber while the interstitial bone to the matrix. For example, there have been several studies addressing the mechanical properties of cortical bone based on this point of view (Hogan 1992, Aoubiza et al. 1996). Our interest in cortical bone mechanics stems from the characterization and mechanisms of microdamage such as microcracks in cortical bone. The exponential increase of microdamage in cortical bone tissue has been implicated in increased bone fragility with aging (Schaffler et al. 1995). None of these above mentioned techniques can be conveniently used for our long term study on cortical bone damage mechanics. Recently, significant advances have been made in the mechanics of composite materials. For example, a generalized self-consistent formulation for effective mechanical properties of composites have been developed such that it can apply to the case where the volume fraction of fibers is as high as 80–90% (Huang et al. 1994). In addition, microcracks can be easily included for damage mechanics or fracture mechanics analysis. The objective of this paper is to develop a general scheme for a cortical bone composite model based on the generalized self-consistent method for calculation of effective elastic properties.

Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity models to probe cellular and molecular interactions underlying developmental processes. In this study, we co-cultured human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (MSCs) under various environmental conditions to elicit synergistic interactions leading to the colocalized development of capillary-like and bone-like tissues. Cells were encapsulated at the 1:1 ratio in fibrin gel to screen compositions of endothelial growth medium (EGM) and osteogenic medium (OM). It was determined that, to form both tissues, co-cultures should first be supplied with EGM followed by a 1:1 cocktail of the two media types containing bone morphogenetic protein-2. Subsequent studies of HUVECs and MSCs cultured in decellularized, trabecular bone scaffolds for 6 weeks assessed the effects on tissue construct of both temporal variations in growth-factor availability and addition of fresh cells. The resulting grafts were implanted subcutaneously into nude mice to determine the phenotype stability and functionality of engineered vessels. Two important findings resulted from these studies: (i) vascular development needs to be induced prior to osteogenesis, and (ii) the addition of additional hMSCs at the osteogenic induction stage improves both tissue outcomes, as shown by increased bone volume fraction, osteoid deposition, close proximity of bone proteins to vascular networks, and anastomosis of vascular networks with the host vasculature. Interestingly, these observations compare well with what has been described for native development. We propose that our cultivation system can mimic various aspects of endothelial cell-osteogenic precursor interactions in vivo, and could find utility as a model for studies of heterotypic cellular interactions that couple blood vessel formation with osteogenesis., Funding support of this work was provided by the National Institutes of Health (DE161525 and EB02520 to GVN), the Orthopaedic Research Society (ORS) Career Development Award (to WLG), and the Fundacao para a Ciencia e a Tecnologia of Portugal (PhD grant to CC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The sympathetic nervous system regulates bone mass accrual by signaling via CREB and ATF4 in osteoblasts to promote proliferation and RANKL production, respectively., The sympathetic nervous system, whose activity is regulated by leptin signaling in the brain, is a major regulator of bone mass accrual. To determine the identity of the cell type in which the sympathetic tone signals to inhibit bone mass accrual, we performed a systematic, cell-specific analysis of the function of the β2 adrenergic receptor (Adrβ2) and various genes implicated in the pathway in the mouse. This was followed by leptin intracerebroventricular (ICV) infusion and bone histomorphometric analyses of bone parameters. We show that the sympathetic tone signals in the osteoblasts to inhibit CREB (cAMP-responsive element-binding protein) phosphorylation and thus decrease osteoblast proliferation and to promote ATF4 phosphorylation and thus increase RANKL (receptor activator of NF-κB ligand) expression, which then stimulates osteoclast differentiation. Leptin ICV infusion in various mouse models established that leptin-dependent inhibition of bone mass accrual relies on both transcriptional events taking place in osteoblasts. Thus, this study formally identifies the osteoblast as the major cell type in which the molecular events triggered by the sympathetic regulation of bone mass accrual take place. As such, it suggests that inhibiting sympathetic signaling could be beneficial in the treatment of low bone mass conditions.

quality profile of subjects with and without non-traumatic hip fracture non-invasively. Methods: Hip fractured postmenopausal women (n=25) and ageand gender-matched normal controls (n=38) were recruited. The bone quality at the non-dominant distal radius and non-fracture (fracture group)/non-dominant (control group) of distal tibia were measured by HR-pQCT (XtremeCT, Scanco Medical AG). HR-pQCT, with 82 mm resolution, provided volumetric trabecular BMD (Dtrab), cortical BMD (Dcort), bone to tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). Independent t-test was used for between-group analysis. Results: Similar age and body weight were found in both groups. At the distal tibia, all vBMDs, including total BMD, Dtrab and Dcort, were significantly lower in the hip fracture (HF) group (−26.2 to −7.5%; all, p

INTRODUCTION This Special Session “Biomechanics from Molecules, Cells, Tissues to Organs and Tissue Regeneration” has organized by a diverse group of biomechanics researchers in the United States of America. Most people in this group have heritages rooted in mainland of China and are performing the state of art biomechanics research and education in the United States of America. They have been actively involved in the scientific and educational exchanges in biomechanics research and education between Mainland China and the United States of America. Since 2001, they have been organizing and participating in China Overseas Workshop on Biomechanics (2001 in Beijing, 2004 in Beijing and Shanghai, and 2007 planned in Guangzhou). The third China Overseas Workshop on Biomechanics will be held in Guangzhou, Guangdong Province, China (July 4-7, 2007). This international Workshop has been listed as one of the satellite conference of ISB 2007. The organizers and delegates of the Workshop treasure these unique opportunities brought by the ISB 2007 organizing committee and are privileged to organize the special session of “Biomechanics from Molecules, Cells, Tissues to Organs and Tissue Regeneration”.

Summary In October 2013, the International Combined Orthopaedic Research Societies (ICORS; http://i-cors.org ) was founded with inaugural member organisations from the previous Combined Orthopaedic Research Society, which had sponsored combined meetings for more than 2 decades. The ICORS is dedicated to the stimulation of orthopaedic and musculoskeletal research in fields such as biomedical engineering, biology, chemistry, and veterinary and human clinical research. The ICORS seeks to facilitate communication with member organisations to enhance international research collaborations and to promote the development of new international orthopaedic and musculoskeletal research organisations. Through new categories of membership, the ICORS represents the broadest coalition of orthopaedic research organisations globally.

SummaryBone remodeling is regulated by various neuronal inputs, including sympathetic tone, which is known to inhibit bone mass accrual. This aspect of sympathetic nervous system function raises the prospect that the other arm of the autonomic nervous system, the parasympathetic nervous system, may also affect bone remodeling. Here, we use various mutant mouse strains, each lacking one of the muscarinic receptors that mediate parasympathetic activity, to show that the parasympathetic nervous system acting through the M3 muscarinic receptor is a positive regulator of bone mass accrual, increasing bone formation and decreasing bone resorption. Gene expression studies, cell-specific gene deletion experiments, and analysis of compound mutant mice showed that the parasympathetic nervous system favors bone mass accrual by acting centrally and by decreasing the sympathetic tone. By showing that both arms of the autonomic nervous system affect bone remodeling, this study further underscores the importance of neuronal regulation of bone.

Spinal cord injury (SCI) results in marked atrophy of sublesional skeletal muscle and substantial loss of bone. In this study, the effects of prolonged electrical stimulation (ES) and/or testosterone enanthate (TE) on muscle mass and bone formation in a rat model of SCI were tested. Compared to sham-transected animals, a significant reduction of the mass of soleus, plantaris and extensor digitorum longus (EDL) muscles was observed in animals 6 weeks post-SCI. Notably, ES or ES + TE resulted in the increased mass of the EDL muscles. ES or ES + TE significantly decreased mRNA levels of muscle atrophy markers (e.g., MAFbx and MurF1) in the EDL. Significant decreases in bone mineral density (BMD) (−27%) and trabecular bone volume (−49.3%) at the distal femur were observed in animals 6 weeks post injury. TE, ES and ES + TE treatment significantly increased BMD by +6.4%, +5.4%, +8.5% and bone volume by +22.2%, and +56.2% and+ 60.2%, respectively. Notably, ES alone or ES + TE resulted in almost complete restoration of cortical stiffness estimated by finite element analysis in SCI animals. Osteoblastogenesis was evaluated by colony-forming unit-fibroblastic (CFU-F) staining using bone marrow mesenchymal stem cells obtained from the femur. SCI decreased the CFU-F+ cells by −56.8% compared to sham animals. TE or ES + TE treatment after SCI increased osteoblastogenesis by +74.6% and +67.2%, respectively. An osteoclastogenesis assay revealed significantly increased TRAP+ multinucleated cells (+34.8%) in SCI animals compared to sham animals. TE, ES and TE + ES treatment following SCI markedly decreased TRAP+ cells by −51.3%, −40.3% and −46.9%, respectively. Each intervention greatly reduced the ratio of RANKL to OPG mRNA of sublesional long bone. Collectively, our findings demonstrate that after neurologically complete paralysis, dynamic muscle resistance exercise by ES reduced muscle atrophy, downregulated genes involved in muscle wasting, and restored mechanical loading to sublesional bone to a degree that allowed for the preservation of bone by inhibition of bone resorption and/or by facilitating bone formation.