Evolutionary Patterns of Bone Histology and Bone Compactness in Xenarthran Mammal Long Bones

PubMed Central

Straehl, Fiona R.; Scheyer, Torsten M.; Forasiepi, Analía M.; MacPhee, Ross D.; Sánchez-Villagra, Marcelo R.

2013-01-01

Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness. PMID:23874932

Local Bisphosphonate Treatment Increases Fixation of Hydroxyapatite-Coated Implants Inserted with Bone Compaction

PubMed Central

Jakobsen, Thomas; Baas, Jørgen; Kold, Søren; Bechtold, Joan E.; Elmengaard, Brian; Søballe, Kjeld

2013-01-01

It has been shown that fixation of primary cementless joint replacement can independently be enhanced by either: (1) use of hydroxyapatite (HA) coated implants, (2) compaction of the peri-implant bone, or (3) local application of bisphosphonate. We investigated whether the combined effect ofHAcoating and bone compaction can be further enhanced with the use of local bisphosphonate treatment .HA-coated implants were bilaterally inserted into the proximal tibiae of 10 dogs. On one side local bisphosphonate was applied prior to bone compaction. Saline was used as control on the contralateral side. Implants were evaluated with histomorphometry and biomechanical pushout test. We found that bisphosphonate increased the peri-implant bone volume fraction (1.3-fold), maximum shear strength (2.1-fold), and maximum shear stiffness (2.7-fold). No significant difference was found in bone-to-implant contact or total energy absorption. This study indicates that local alendronate treatment can further improve the fixation of porous-coated implants that have also undergone HA-surface coating and peri-implant bone compaction. PMID:18752278

A procedure for preparing undecalcified and unembedded bone sections for light microscopy.

PubMed

Mancini, M; Spoliti, M; Botti, F; Ragazzoni, E; Cocchia, D

1997-07-01

We have developed a procedure for light microscopic investigation of undecalcified and unembedded bone sections. Biopsy samples of human metatarsus and femur and rat femur were fixed in aldehydes and sectioned with a cutting machine equipped with a diamond saw blade. Free sections 100-150 microns thick, stained with toluidine blue and von Kossa, did not show artifacts following the cutting, and the spatial relations of mineralized and nonmineralized components remained intact. Compact and trabecular bone, bone marrow and all cell types appeared well preserved and easily recognizable. Our procedure provides a simple and rapid method for preparing bone sections which undergo no chemical treatment other than fixation. This method is a useful alternative to standard histological protocols for studying bone specimens.

Anatomy, histology and elemental profile of long bones and ribs of the Asian elephant (Elephas maximus).

PubMed

Nganvongpanit, Korakot; Siengdee, Puntita; Buddhachat, Kittisak; Brown, Janine L; Klinhom, Sarisa; Pitakarnnop, Tanita; Angkawanish, Taweepoke; Thitaram, Chatchote

2017-09-01

This study evaluated the morphology and elemental composition of Asian elephant (Elephas maximus) bones (humerus, radius, ulna, femur, tibia, fibula and rib). Computerized tomography was used to image the intraosseous structure, compact bones were processed using histological techniques, and elemental profiling of compact bone was conducted using X-ray fluorescence. There was no clear evidence of an open marrow cavity in any of the bones; rather, dense trabecular bone was found in the bone interior. Compact bone contained double osteons in the radius, tibia and fibula. The osteon structure was comparatively large and similar in all bones, although the lacuna area was greater (P < 0.05) in the femur and ulna. Another finding was that nutrient foramina were clearly present in the humerus, ulna, femur, tibia and rib. Twenty elements were identified in elephant compact bone. Of these, ten differed significantly across the seven bones: Ca, Ti, V, Mn, Fe, Zr, Ag, Cd, Sn and Sb. Of particular interest was the finding of a significantly larger proportion of Fe in the humerus, radius, fibula and ribs, all bones without an open medullary cavity, which is traditionally associated with bone marrow for blood cell production. In conclusion, elephant bones present special characteristics, some of which may be important to hematopoiesis and bone strength for supporting a heavy body weight.

Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

PubMed

Maggiano, Corey M; Maggiano, Isabel S; Tiesler, Vera G; Chi-Keb, Julio R; Stout, Sam D

2016-01-01

This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations. © 2015 Anatomical Society.

Machining of a bioactive nanocomposite orthopedic fixation device.

PubMed

Sparnell, Amie; Aniket; El-Ghannam, Ahmed

2012-08-01

Bioactive ceramics bond to bone and enhance bone formation. However, they have poor mechanical properties which restrict their machinability as well as their application as load bearing implants. The goal of this study was to machine bioactive fixation screws using a silica-calcium phosphate nanocomposite (SCPC50). The effect of compact pressure, holding time, and thermal treatment on the microstructure, machinability, and mechanical properties of SCPC50 cylinders were investigated. Samples prepared by powder metallurgy technique at compact pressure range of 100-300 MPa and treated at 900°C/1 h scored a poor machinability rating of (1/5) due to the significant formation of amorphous silicate phase at the grain boundaries. On the other hand, lowering of compact pressure and sintering temperature to 30 MPa/3 h and 700°C/2 h, respectively, minimized the formation of the amorphous phase and raised the machinability rating to (5/5). The modulus of elasticity and ultimate strength of machinable SCPC50 were 10.8 ± 2.0 GPa and 72.8 ± 22.8 MPa, respectively, which are comparable to the corresponding values for adult human cortical bone. qRT-PCR analyses showed that bone cells attached to SCPC50 significantly upregulated osteocalcin mRNA expression as compared to the cells on Ti-6Al-4V. Moreover, cells attached to SCPC50 produced mineralized bone-like tissue within 8 days. On the other hand, cells attached to Ti-6Al-4V failed to produce bone mineral under the same experimental conditions. Results of the study suggest that machinable SCPC50 has the potential to serve as an attractive new material for orthopedic fixation devices. Copyright © 2012 Wiley Periodicals, Inc.

Effects of compaction pressure and particle shape on the porosity and compression mechanical properties of sintered Ti6Al4V powder compacts for hard tissue implantation.

PubMed

Güden, Mustafa; Celik, Emrah; Hizal, Alpay; Altindiş, Mustafa; Cetiner, Sinan

2008-05-01

Sintered Ti6Al4V powder compacts potentially to be used in implant applications were prepared using commercially available spherical and angular powders (100-200 mum) within the porosity range of 34-54%. Cylindrical green powder compacts were cold compacted at various pressures and then sintered at 1200 degrees C for 2 h. The final percent porosity and mean pore sizes were determined as functions of the applied compaction pressure and powder type. The mechanical properties were investigated through compression testing. Results have shown that yield strength of the powder compacts of 40-42% porosity was comparable with that of human cortical bone. As compared with previously investigated Ti powder compacts, Ti6Al4V powder compacts showed higher strength at similar porosity range. Microscopic observations on the failed compact samples revealed that failure occurred primarily by the separation of interparticle bond regions in the planes 45 degrees to the loading axis. Copyright 2007 Wiley Periodicals, Inc.

Alteration of mineral crystallinity and collagen cross-linking of bones in osteopetrotic toothless (tl/tl) rats and their improvement after treatment with colony stimulating factor-1

NASA Technical Reports Server (NTRS)

Wojtowicz, A.; Dziedzic-Goclawska, A.; Kaminski, A.; Stachowicz, W.; Wojtowicz, K.; Marks, S. C. Jr; Yamauchi, M.

1997-01-01

A common feature of various types of mammalian osteopetroses is a marked increase in bone mass accompanied by spontaneous bone fractures. The toothless (tl/tl) rat osteopetrotic mutation is characterized by drastically reduced bone resorption due to a profound deficiency of osteoclasts and their precursors. An altered bone morphology has also been observed. The mutants cannot be cured by bone marrow transplantation, but skeletal defects are greatly reduced after treatment with colony stimulating factor 1 (CSF-1). The objectives of this study were to characterize mineral and collagen matrices in cancellous and compact bone isolated from long bones of 6-week-old normal littermates, tl/tl osteopetrotic mutants and mutants (tl/tl) treated with CSF-1. There were no differences in bone mineral content, but a significant decrease in the crystallinity of mineral evaluated by the method based on electron paramagnetic resonance spectrometry was observed in all bones of tl/tl mutants as compared to that of controls. Within the collagen matrix, slight decreases in the labile cross-links, but significant increases in the content of the stable cross-links, pyridinoline, and deoxypyridinoline, were observed in both cancellous and compact bone of osteopetrotic mutants. In tl/tl mutants treated with human recombinant CSF-1, the normalization of the crystallinity of bone mineral as well as collagen cross-links was found. Our results indicate that remodeling of bone matrix in tl/tl mutants is highly suppressed, but that after treatment with CSF-1, this activity recovers significantly. Taken together, these data provide further support for the hypothesis that CSF-1 is an essential factor for normal osteoclast differentiation and bone remodelling.

In vitro effectiveness of antimicrobial photodynamic therapy (APDT) using a 660 nm laser and malachite green dye in Staphylococcus aureus biofilms arranged on compact and cancellous bone specimens.

PubMed

Rosa, Luciano Pereira; da Silva, Francine Cristina; Nader, Sumaia Alves; Meira, Giselle Andrade; Viana, Magda Souza

2014-11-01

The aim of this study was to evaluate the in vitro effectiveness of antimicrobial photodynamic therapy (APDT) using a 660 nm visible laser combined with malachite green (MG) dye in the inactivation of Staphylococcus aureus (ATCC 25923) biofilms formed within compact and cancellous bone specimens. Specimens of 80 compact bones and 80 cancellous bones were contaminated with a standard suspension of S. aureus and incubated for 14 days at 37 °C to allow for the formation of biofilms. The specimens were divided into the following groups (n = 10) according to the treatment conditions: PS-L - (control - no treatment), PS+L - (only MG for 5 min), PS-L + 90 (only laser irradiation for 90 s), PS-L + 180 (only laser irradiation for 180 s), PS-L + 300 (only laser irradiation for 300 s), APDT90 (APDT for 90 s), APDT180 (APDT for 180 s), and APDT300 (APDT for 300 s). The findings were statistically analyzed using an ANOVA 5%. All of the experimental groups were significantly different from the control group for both the compact and cancellous bone specimens. The compact bone specimens that received APDT treatment (for either 90, 180, or 300 s) showed reductions in the log10 CFU/ml of S. aureus by a magnitude of 4 log10. Cancellous bone specimens treated with 300 s of APDT showed the highest efficacy, and these specimens had a reduction in S. aureus CFU/ml by a factor of 3 log10. APDT treatment using these proposed parameters in combination with MG was effective at inactivating S. aureus biofilms in compact and cancellous bone specimens.

Enhanced osteoblast adhesion on nanostructured selenium compacts for anti-cancer orthopedic applications.

PubMed

Tran, Phong; Webster, Thomas J

2008-01-01

Metallic bone implants possess numerous problems limiting their long-term efficacy, such as poor prolonged osseointegration, stress shielding, and corrosion under in vivo environments. Such problems are compounded for bone cancer patients since numerous patients receive orthopedic implants after cancerous bone resection. Unfortunately, current orthopedic materials were not originally developed to simultaneously increase healthy bone growth (as in traditional orthopedic implant applications) while inhibiting cancerous bone growth. The long-term objective of the present research is to investigate the use of nano-rough selenium to prevent bone cancer from re-occurring while promoting healthy bone growth for this select group of cancer patients. Selenium is a well known anti-cancer chemical. However, what is not known is how healthy bone cells interact with selenium. To determine this, selenium, spherical or semispherical shots, were pressed into cylindrical compacts and these compacts were then etched using 1N NaOH to obtain various surface structures ranging from the micron, submicron to nano scales. Changes in surface chemistry were also analyzed. Through these etching techniques, results of this study showed that biologically inspired surface roughness values were created on selenium compacts to match that of natural bone roughness. Moreover, results showed that healthy bone cell adhesion increased with greater nanometer selenium roughness (more closely matching that of titanium). In this manner, this study suggests that nano-rough selenium should be further tested for orthopedic applications involving bone cancer treatment.

Enhanced osteoblast adhesion on nanostructured selenium compacts for anti-cancer orthopedic applications

PubMed Central

Tran, Phong; Webster, Thomas J

2008-01-01

Metallic bone implants possess numerous problems limiting their long-term efficacy, such as poor prolonged osseointegration, stress shielding, and corrosion under in vivo environments. Such problems are compounded for bone cancer patients since numerous patients receive orthopedic implants after cancerous bone resection. Unfortunately, current orthopedic materials were not originally developed to simultaneously increase healthy bone growth (as in traditional orthopedic implant applications) while inhibiting cancerous bone growth. The long-term objective of the present research is to investigate the use of nano-rough selenium to prevent bone cancer from re-occurring while promoting healthy bone growth for this select group of cancer patients. Selenium is a well known anti-cancer chemical. However, what is not known is how healthy bone cells interact with selenium. To determine this, selenium, spherical or semispherical shots, were pressed into cylindrical compacts and these compacts were then etched using 1N NaOH to obtain various surface structures ranging from the micron, submicron to nano scales. Changes in surface chemistry were also analyzed. Through these etching techniques, results of this study showed that biologically inspired surface roughness values were created on selenium compacts to match that of natural bone roughness. Moreover, results showed that healthy bone cell adhesion increased with greater nanometer selenium roughness (more closely matching that of titanium). In this manner, this study suggests that nano-rough selenium should be further tested for orthopedic applications involving bone cancer treatment. PMID:18990948

Research of mechanics of the compact bone microvolume and porous ceramics under uniaxial compression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolmakova, T. V., E-mail: kolmakova@ftf.tsu.ru; Buyakova, S. P., E-mail: sbuyakova@ispms.tsc.ru; Kul’kov, S. N., E-mail: kulkov@ms.tsc.ru

2015-11-17

The research results of the mechanics are presented and the effective mechanical characteristics under uniaxial compression of the simulative microvolume of the compact bone are defined subject to the direction of the collagen-mineral fibers, porosity and mineral content. The experimental studies of the mechanics are performed and the effective mechanical characteristics of the produced porous zirconium oxide ceramics are defined. The recommendations are developed on the selection of the ceramic samples designed to replace the fragment of the compact bone of a definite structure and mineral content.

Antimicrobial photodynamic inactivation of Staphylococcus aureus biofilms in bone specimens using methylene blue, toluidine blue ortho and malachite green: An in vitro study.

PubMed

Rosa, Luciano Pereira; da Silva, Francine Cristina; Nader, Sumaia Alves; Meira, Giselle Andrade; Viana, Magda Souza

2015-05-01

To evaluate the in vitro effectiveness of APDI with a 660 nm laser combined with methylene blue (MB), toluidine blue ortho (TBO) and malachite green (MG) dyes to inactivate Staphylococcus aureus (ATCC 25923) biofilms in compact and cancellous bone specimens. Eighty specimens of compact and 80 of cancellous bone were contaminated with a standard suspension of the microorganism and incubated for 14 days at 37°C to form biofilms. After this period, the specimens were divided into groups (n=10) according to established treatment: PS-L- (control - no treatment); PSmb+L-, PStbo+L-, PSmg+L- (only MB, TBO or MG for 5 min in the dark); PS-L+ (only laser irradiation for 180 s); and APDImb, APDItbo and APDImg (APDI with MB, TBO or MG for 180 s). The findings were statistically analyzed by ANOVA at 5% significance levels. All experimental treatments showed significant reduction of log CFU/mL S. aureus biofilms when compared with the control group for compact and cancellous bones specimens; the APDI group's treatment was more effective. The APDI carried out for the compact specimens showed better results when compared with cancellous specimens at all times of application. For the group of compact bone, APDImg showed greater reductions in CFU/mL (4.46 log 10). In the group of cancellous bone, the greatest reductions were found in the APDImb group (3.06 log 10). APDI with methylene blue, toluidine blue ortho and malachite green dyes and a 660 nm laser proved to be effective in the inactivation of S. aureus biofilms formed in compact and cancellous bone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transplantation of stem cells from human exfoliated deciduous teeth for bone regeneration in the dog mandibular defect

PubMed Central

Behnia, Ali; Haghighat, Abbas; Talebi, Ardeshir; Nourbakhsh, Nosrat; Heidari, Fariba

2014-01-01

AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth (SHED) transplanted for bone regeneration in the dog mandibular defect. METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-and-through defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level. RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue (P = 0.248), woven bone (P = 0.248) and compact bone (P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period. CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs. PMID:25258673

In vivo performance of selective electron beam-melted Ti-6Al-4V structures.

PubMed

Ponader, Sabine; von Wilmowsky, Cornelius; Widenmayer, Martin; Lutz, Rainer; Heinl, Peter; Körner, Carolin; Singer, Robert F; Nkenke, Emeka; Neukam, Friedrich W; Schlegel, Karl A

2010-01-01

Highly porous titanium structures are widely used for maxillofacial and orthopedic surgery because of their excellent mechanical properties similar to those of human bone and their facilitation of bone ingrowth. In contrast to common methods, the generation of porous titaniumproducts by selective electron beam melting (SEBM), an additive manufacturing technology, overcomes difficulties concerning the extreme chemical affinity of liquid titanium to atmospheric gases which consequently leads to strongly reduced ductility of the metal. The purpose of this study was to assess the suitability of a smooth compact and a porous Ti-6Al-4V structure directly produced by the SEBM process as scaffolds for bone formation. SEBM-processed titanium implants were placed into defects in the frontal skull of 15 domestic pigs. To evaluate the direct contact between bone and implant surfaces and to assess the ingrowth of osseous tissue into the porous structure, microradiographs and histomorphometric analyses were performed 14, 30, and 60 days after surgery. Bone ingrowth increased significantly during the period of this study. After 14 days the most outer regions of the implants were already filled with newly formed bone tissue (around 14%). After 30 days the bone volume inside the implants reached almost 30% and after 60 days abundant bone formation inside the implants attained 46%. During the study only scarce bone-implant contact was found around all implants, which did not exceed 9% around compact specimens and 6% around porous specimens after 60 days. This work demonstrates that highly porous titanium implants with excellent interconnectivity manufactured using the SEBM method are suitable scaffolds for bone ingrowth. This technique is a good candidate for orthopedic and maxillofacial applications.

THE EFFECT OF STRAIN RATE ON FRACTURE TOUGHNESS OF HUMAN CORTICAL BONE: A FINITE ELEMENT STUDY

PubMed Central

Ural, Ani; Zioupos, Peter; Buchanan, Drew; Vashishth, Deepak

2011-01-01

Evaluating the mechanical response of bone under high loading rates is crucial to understanding fractures in traumatic accidents or falls. In the current study, a computational approach based on cohesive finite element modeling was employed to evaluate the effect of strain rate on fracture toughness of human cortical bone. Two-dimensional compact tension specimen models were simulated to evaluate the change in initiation and propagation fracture toughness with increasing strain rate (range: 0.08 to 18 s−1). In addition, the effect of porosity in combination with strain rate was assessed using three-dimensional models of microcomputed tomography-based compact tension specimens. The simulation results showed that bone’s resistance against the propagation of fracture decreased sharply with increase in strain rates up to 1 s−1 and attained an almost constant value for strain rates larger than 1 s−1. On the other hand, initiation fracture toughness exhibited a more gradual decrease throughout the strain rates. There was a significant positive correlation between the experimentally measured number of microcracks and the fracture toughness found in the simulations. Furthermore, the simulation results showed that the amount of porosity did not affect the way initiation fracture toughness decreased with increasing strain rates, whereas it exacerbated the same strain rate effect when propagation fracture toughness was considered. These results suggest that strain rates associated with falls lead to a dramatic reduction in bone’s resistance against crack propagation. The compromised fracture resistance of bone at loads exceeding normal activities indicates a sharp reduction and/or absence of toughening mechanisms in bone during high strain conditions associated with traumatic fracture. PMID:21783112

Aging of microstructural compartments in human compact bone

NASA Technical Reports Server (NTRS)

Akkus, Ozan; Polyakova-Akkus, Anna; Adar, Fran; Schaffler, Mitchell B.

2003-01-01

Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue. In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes "fully mineralized." The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the osteons and similar to the "fully mineralized" stage of primary bone. The results of this study demonstrated that unremodeled compartments of bone grow older through maturation and growth of mineral crystals in a protracted fashion. However, the secondary osteonal remodeling impedes this aging process and maintains the mean tissue age fairly constant over decades. Therefore, slowing of remodeling may lead to brittle bone tissue through accumulation of fully mineralized tissue fragments.

Measuring the stopping power of α particles in compact bone for BNCT

NASA Astrophysics Data System (ADS)

Provenzano, L.; Rodríguez, L. M.; Fregenal, D.; Bernardi, G.; Olivares, C.; Altieri, S.; Bortolussi, S.; González, S. J.

2015-01-01

The stopping power of α particles in thin films of decalcified sheep femur, in the range of 1.5 to 5.0 MeV incident energy, was measured by transmission of a backscattered beam from a heavy target. Additionally, the film elemental composition was determined by Rutherford Backscattering Spectrometry (RBS). These data will be used to measure boron concentration in thin films of bone using a spectrometry technique developed by the University of Pavia, since the concentration ratio between healthy tissue and tumor is of fundamental importance in Boron Neutron Capture Therapy (BNCT). The present experimental data are compared with numerical simulation results and with tabulated stopping power data of non-decalcified human bone.

Effectiveness of antimicrobial photodynamic therapy using a 660 nm laser and methyline blue dye for inactivating Staphylococcus aureus biofilms in compact and cancellous bones: An in vitro study.

PubMed

Rosa, Luciano Pereira; Silva, Francine Cristina da; Nader, Sumaia Alves; Meira, Giselle Andrade; Viana, Magda Souza

2015-06-01

New therapeutic modalities such as antimicrobial photodynamic therapy (APDT) has been investigated in order to be a valid alternative to the treatment of infections caused by different microorganisms. This work evaluated the in vitro effectiveness of Antimicrobial Photodynamic Therapy (APDT) using 660 nm laser combined with methylene blue dye to inactivate Staphylococcus aureus (ATCC 25923) biofilms in compact and cancellous bones specimens. Eighty specimens of compact bone and 80 specimens of cancellous bone were contaminated with a standard suspension of S. aureus and incubated for 14 days at 37°C to induce the formation of biofilms. The specimens were then divided into groups (n = 10) according to the established treatment: PS-L- (control--no treatment), PS+L- (only AM for 5 min in the dark), PS-L+90 (only laser irradiation for 90 s), PS-L+180 (only laser irradiation for 180 s), PS-L+300 (only laser irradiation for 300 s), APDT90 (APDT for 90 s), APDT180 (APDT for 180 s), and APDT300 (APDT for 300 s). The findings were statistically analyzed by ANOVA 5%. All of the experimental treatments showed a significant reduction (log 10 CFU/mL) of S. aureus biofilms in compact and cancellous bones specimens compared with the control group, and the APDT group was the most effective. Compact specimens treated with APDT showed the greatest reduction in biofilms compared with cancellous specimens, regardless of length of treatment. APDT with methylene blue dye and a 660 nm laser proved to be effective in inactivating S. aureus biofilms formed in compact and cancellous bone. Copyright © 2015 Elsevier B.V. All rights reserved.

Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

PubMed

Sroga, Grażyna E; Wu, Ping-Cheng; Vashishth, Deepak

2015-01-01

Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones.

Insulin-Like Growth Factor 1, Glycation and Bone Fragility: Implications for Fracture Resistance of Bone

PubMed Central

Sroga, Grażyna E.; Wu, Ping-Cheng; Vashishth, Deepak

2015-01-01

Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones. PMID:25629402

Depth measurements of drilled holes in bone by laser triangulation for the field of oral implantology

NASA Astrophysics Data System (ADS)

Quest, D.; Gayer, C.; Hering, P.

2012-01-01

Laser osteotomy is one possible method of preparing beds for dental implants in the human jaw. A major problem in using this contactless treatment modality is the lack of haptic feedback to control the depth while drilling the implant bed. A contactless measurement system called laser triangulation is presented as a new procedure to overcome this problem. Together with a tomographic picture the actual position of the laser ablation in the bone can be calculated. Furthermore, the laser response is sufficiently fast as to pose little risk to surrounding sensitive areas such as nerves and blood vessels. In the jaw two different bone structures exist, namely the cancellous bone and the compact bone. Samples of both bone structures were examined with test drillings performed either by laser osteotomy or by a conventional rotating drilling tool. The depth of these holes was measured using laser triangulation. The results and the setup are reported in this study.

Self-fitting shape memory polymer foam inducing bone regeneration: A rabbit femoral defect study.

PubMed

Xie, Ruiqi; Hu, Jinlian; Hoffmann, Oskar; Zhang, Yuanchi; Ng, Frankie; Qin, Tingwu; Guo, Xia

2018-04-01

Although tissue engineering has been attracted greatly for healing of critical-sized bone defects, great efforts for improvement are still being made in scaffold design. In particular, bone regeneration would be enhanced if a scaffold precisely matches the contour of bone defects, especially if it could be implanted into the human body conveniently and safely. In this study, polyurethane/hydroxyapatite-based shape memory polymer (SMP) foam was fabricated as a scaffold substrate to facilitate bone regeneration. The minimally invasive delivery and the self-fitting behavior of the SMP foam were systematically evaluated to demonstrate its feasibility in the treatment of bone defects in vivo. Results showed that the SMP foam could be conveniently implanted into bone defects with a compact shape. Subsequently, it self-matched the boundary of bone defects upon shape-recovery activation in vivo. Micro-computed tomography determined that bone ingrowth initiated at the periphery of the SMP foam with a constant decrease towards the inside. Successful vascularization and bone remodeling were also demonstrated by histological analysis. Thus, our results indicate that the SMP foam demonstrated great potential for bone regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

A light and scanning electron microscopic evaluation of electro-discharge-compacted porous titanium implants in rabbit tibia.

PubMed

Drummond, J F; Dominici, J T; Sammon, P J; Okazaki, K; Geissler, R; Lifland, M I; Anderson, S A; Renshaw, W

1995-01-01

This study used light and scanning electron microscopic (SEM) histomorphometric methods to quantitate the rate of osseointegration of totally porous titanium alloy (Ti-6Al-4V) implants prepared by a novel fabrication technique--electrodischarge compaction (EDC). EDC was used to fuse 150-250-micrometer spherical titanium alloy beads into 4 X 6 mm cylindrical implants through application of a 300-microsecond pulse of high-voltage/high-current density. Two sterilized implants were surgically placed into each tibia of 20 New Zealand white rabbits and left in situ for periods corresponding to 2, 4, 8, 12, and 24 weeks. At each time point, 4 rabbits were humanely killed, and the implants with surrounding bone were removed, fixed, and sectioned for light and SEM studies. The degree of osseointegration was quantitated by means of a True Grid Digitizing Pad and Jandel Scan Version 3.9 software on an IBM PS/2 computer. The total pore area occupied by bone was divided by the total pore area available for bone ingrowth, and a Bone Ingrowth Factor (BIF) was calculated as a percent. The light microscopic results showed BIFs of 4% at week 2, 47% at week 4, 62% at week 8, 84% at week 12, and greater than 90% at week 24. The SEM results showed BIFs of 5% at week 2, 34% at week 4, 69% at week 8, 75% at week 12, and in excess of 90% at week 24. The results of this study show that EDC implants are biocompatible and support rapid osseointegration in the rabbit tibia and suggest that, after additional studies, they may be suitable for use as dental implants in humans.

Mechanical Behavior of Polymer Nano Bio Composite for Orthopedic Implants

NASA Astrophysics Data System (ADS)

Marimuthu, K., Dr.; Rajan, Sankar

2018-04-01

The bio-based polymer composites have been the focus of many scientific and research projects, as well as many commercial programs. In recent years, scientists and engineers have been working together to use the inherent strength and performance of the new class of bio-based composites which is compactable with human body and can act as a substitute for living cells. In this stage the polymer composites also stepped into human bone implants as a replacement for metallic implants which was problems like corrosion resistance and high cost. The polymer composite have the advantage that it can be molded to the required shape, the polymers have high corrosion resistance, less weight and low cost. The aim of this research is to develop and analyze the suitable bio compactable polymer composite for human implants. The nano particles reinforced polymer composites provides good mechanical properties and shows good tribological properties especially in the total hip and knee replacements. The graphene oxide powders are bio compactable and acts as anti biotic. GO nano powder where reinforced into High-density polyethylene in various weight percentage of 0.5% to 2%. The performance of GO nano powder shows better tribological properties. The material produced does not cause any pollution to the environment and at the same time it can be bio compactable and sustainable. The product will act environmentally friendly.

Determination of spatial distribution of increase in bone temperature during drilling by infrared thermography: preliminary report.

PubMed

Augustin, Goran; Davila, Slavko; Udiljak, Toma; Vedrina, Denis Stjepan; Bagatin, Dinko

2009-05-01

During the drilling of the bone, the temperature could increase above 47 degrees C and cause irreversible osteonecrosis. The spatial distribution of increase in bone temperature could only be presumed using several thermocouples around the drilling site. The aim of this study was to use infrared thermographic camera for determination of spatial distribution of increase in bone temperature during drilling. One combination of drill parameters was used (drill diameter 4.5 mm; drill speed 1,820 rpm; feed-rate 84 mm/min; drill point angle 100 degrees) without external irrigation on room temperature of 26 degrees C. The increase in bone temperature during drilling was analyzed with infrared thermographic camera in two perpendicular planes. Thermographic pictures were taken before drilling, during drilling with measurement of maximal temperature values and after extraction of the drill from the bone. The thermographic picture shows that the increase in bone temperature has irregular shape with maximal increase along cortical bone, which is the most compact component of the bone. The width of this area with the temperature above critical level is three times broader than the width of cortical bone. From the front, the distribution of increase in bone temperature follows the form of the cortical bone (segment of a ring), which is the most compact part and causes the highest resistance to drilling and subsequent friction. Thermography showed that increase in bone temperature spreads through cortical bone, which is the most compact and dense part, and generates highest frictional heat during drilling. The medullar cavity, because of its gelatinous structure, contributes only to thermal dissipation.

Preparation of the Femoral Bone Cavity for Cementless Stems: Broaching vs Compaction. A Five-Year Randomized Radiostereometric Analysis and Dual Energy X-Ray Absorption Study.

PubMed

Hjorth, Mette H; Kold, Søren; Søballe, Kjeld; Langdahl, Bente L; Nielsen, Poul T; Christensen, Poul H; Stilling, Maiken

2017-06-01

Short-term experimental and animal studies have confirmed superior fixation of cementless implants inserted with compaction compared to broaching of the cancellous bone. Forty-four hips in 42 patients (19 men) were randomly operated using cementless hydroxyapatite-coated Bi-Metric stems. Patients were followed with radiostereometric analysis at baseline, 6 and 12 weeks, 1, 2, and 5 years, and measurements of periprosthetic bone mineral density at baseline, 1, 2, and 5 years. Complications during the study period and clinical outcome measures of Harris Hip Score were recorded at mean 7 years (5-8.8) after surgery. Absolute migrations of medio/lateral translations between the broaching group and the compaction group of mean 0.14 mm (standard deviation [SD] 0.10) vs mean 0.30 mm (SD 0.27) (P = .01) at 1 year, and of mean 0.13 mm (SD 0.10) vs 0.34 mm (0.31) (P = .01) at 5 years were different. Absolute valgus/varus rotations of mean 0.12° (SD 0.13°) in the broaching group were less than mean 0.35° (0.45°) in the compaction group (P < .01) at 1 year, but at 5 years no difference was observed (P = .19). Subsidence and retroversion were similar between groups at all follow-ups (P > .13). The compaction group had significantly less bone loss than the broaching group in Gruen zone 3 (distal-lateral to the stem) at 1 and 5 years. No further differences in bone mineral density changes were found between groups up to 5 years after surgery. Complications throughout the period and clinical outcome measures of Harris Hip Score were similar at 7 years (5-8.8) after surgery. We found increased migration when preparing the bone with compaction compared with broaching in cementless femoral stems. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical properties and biocompatibility of porous titanium scaffolds for bone tissue engineering.

PubMed

Chen, Yunhui; Frith, Jessica Ellen; Dehghan-Manshadi, Ali; Attar, Hooyar; Kent, Damon; Soro, Nicolas Dominique Mathieu; Bermingham, Michael J; Dargusch, Matthew S

2017-11-01

Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human cortical bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 44.2GPa, 24.7GPa and 15.4GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30GPa). The yield strengths for 30% and 40% porosity samples of 221.7MPa and 117MPa are superior to that of human cortical bone (130-180MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

As solid as a rock-comparison of CE- and MPS-based analyses of the petrosal bone as a source of DNA for forensic identification of challenging cranial bones.

PubMed

Kulstein, Galina; Hadrys, Thorsten; Wiegand, Peter

2018-01-01

Short tandem repeat (STR) typing from skeletal remains can be a difficult task. Dependent on the environmental conditions of the provenance of the bones, DNA can be degraded and STR typing inhibited. Generally, dense and compact bones are known to preserve DNA better. Several studies already proved that femora and teeth have high DNA typing success rates. Unfortunately, these elements are not present in all cases involving skeletal remains. Processing partial or singular skeletal elements, it is favorable to select bone areas where DNA preservation is comparably higher. Especially, cranial bones are often accidentally discovered during criminal investigations. The cranial bone is composed of multiple parts. In this examination, we evaluated the potential of the petrous bone for human identification of skeletal remains in forensic case work. Material from different sections of eight unknown cranial bones and-where available-additionally other skeletal elements, collected at the DNA department of the Institute of Legal Medicine in Ulm, Germany, from 2010 to 2017, were processed with an optimized DNA extraction and STR typing strategy. The results highlight that STR typing from the petrous bones leads to reportable profiles in all individuals, even in cases where the analysis of the parietal bone failed. Moreover, the comparison of capillary electrophorese (CE) typing to massively parallel sequencing (MPS) analysis shows that MPS has the potential to analyze degraded human remains and is even capable to provide additional information about phenotype and ancestry of unknown individuals.

Trace and macro elements in the femoral bone as indicators of long-term environmental exposure to toxic metals in European brown bear (Ursus arctos) from Croatia.

PubMed

Lazarus, Maja; Orct, Tatjana; Reljić, Slaven; Sedak, Marija; Bilandžić, Nina; Jurasović, Jasna; Huber, Đuro

2018-05-21

We explored the long-term accumulation of aluminium, strontium, cadmium and lead in the compact and trabecular bone of the femoral epiphysis, metaphysis and diaphysis in 41 brown bears (Ursus arctos) from Croatia. Also, we assessed their influence on macro and trace elements (sodium, magnesium, phosphorus, potassium, calcium, manganese, iron, cobalt, copper, zinc and barium) in bears' bone. There were no sex differences in element levels in general, while age was associated with bone length and levels of all elements, except for cadmium. Elements had different levels depending on the part of the bone sampled. More pronounced differences were observed between the compact and trabecular regions, with higher levels of majority of elements found in compact bone. Moderate to high associations (Spearman coefficient, r S  = 0.59-0.97) were confirmed between calcium and potassium, magnesium, phosphorus, manganese, cobalt, zinc, strontium and lead. Lead levels in the bone were below those known to cause adverse health effects, but in 4 of 41 animals they exceeded baseline levels for domestic animals. The femoral bone of the brown bear reflected the accumulative nature of lead and strontium well, as it did the impairment of bone-forming essential element levels associated with these two elements. However, the distribution pattern of elements along the bone was not uniform, so additional care should be taken when choosing on the part of the bone sampled.

Preparation of the femoral bone cavity in cementless stems: broaching versus compaction

PubMed Central

Hjorth, Mette H; Stilling, Maiken; Søballe, Kjeld; Nielsen, Poul Torben; Christensen, Poul H; Kold, Søren

2016-01-01

Background and purpose — Short-term experimental studies have confirmed that there is superior fixation of cementless implants inserted with compaction compared to broaching of the cancellous bone. Patients and methods — 1-stage, bilateral primary THA was performed in 28 patients between May 2001 and September 2007. The patients were randomized to femoral bone preparation with broaching on 1 side and compaction on the other side. 8 patients declined to attend the postoperative follow-up, leaving 20 patients (13 male) with a mean age of 58 (36–70) years for evaluation. The patients were followed with radiostereometric analysis (RSA) at baseline, at 6 and 12 weeks, and at 1, 2, and 5 years, and measurements of periprosthetic bone mineral density (BMD) at baseline and at 1, 2, and 5 years. The subjective part of the Harris hip score (HHS) and details of complications throughout the observation period were obtained at a mean interval of 6.3 (3.0–9.5) years after surgery. Results — Femoral stems in the compaction group had a higher degree of medio-lateral migration (0.21 mm, 95% CI: 0.03–0.40) than femoral stems in the broaching group at 5 years (p = 0.02). No other significant differences in translations or rotations were found between the 2 surgical techniques at 2 years (p > 0.4) and 5 years (p > 0.7) postoperatively. There were no individual stems with continuous migration. Periprosthetic BMD in the 7 Gruen zones was similar at 2 years and at 5 years. Intraoperative femoral fractures occurred in 2 of 20 compacted hips, but there were none in the 20 broached hips. The HHS and dislocations were similar in the 2 groups at 6.3 (3.0–9.5) years after surgery. Interpretation — Bone compaction as a surgical technique with the Bi-Metric stem did not show the superior outcomes expected compared to conventional broaching. Furthermore, 2 periprosthetic fractures occurred using the compaction technique, so we cannot recommend compaction for insertion of the cementless Bi-Metric stem. PMID:27759486

Vacuum-sintered body of a novel apatite for artificial bone

NASA Astrophysics Data System (ADS)

Tamura, Kenichi; Fujita, Tatsushi; Morisaki, Yuriko

2013-12-01

We produced regenerative artificial bone material and bone parts using vacuum-sintered bodies of a novel apatite called "Titanium medical apatite (TMA®)" for biomedical applications. TMA was formed by chemically connecting a Ti oxide molecule with the reactive [Ca10(PO4)6] group of Hydroxyapatite (HAp). The TMA powders were kneaded with distilled water, and solid cylinders of compacted TMA were made by compression molding at 10 MPa using a stainless-steel vessel. The TMA compacts were dried and then sintered in vacuum (about 10-3 Pa) or in air using a resistance heating furnace in the temperature range 1073-1773 K. TMA compacts were sintered at temperatures greater than 1073 K, thus resulting in recrystallization. The TMA compact bodies sintered in the range 1273-1773 K were converted into mixtures composed of three crystalline materials: α-TCP (tricalcium phosphate), β-TCP, and Perovskite-CaTiO3. The Perovskite crystals were stable and hard. In vacuum-sintering, the Perovskite crystals were transformed into fibers (approximately 1 µm in diameter × 8 µm in length), and the fiber distribution was uniform in various directions. We refer to the TMA vacuum-sintered bodies as a "reinforced composite material with Perovskite crystal fibers." However, in atmospheric sintering, the Perovskite crystals were of various sizes and were irregularly distributed as a result of the effect of oxygen. After sintering temperature at 1573 K, the following results were obtained: the obtained TMA vacuum-sintered bodies (1) were white, (2) had a density of approximately 2300 kg/m3 (corresponding to that of a compact bone or a tooth), and had a thermal conductivity of approximately 31.3 W/(m·K) (corresponding to those of metal or ceramic implants). Further, it was possible to cut the TMA bodies into various forms with a cutting machine. An implant made of TMA and inserted into a rabbit jaw bone was covered by new bone tissues after just one month because of the high biocompatibility of the TMA implant. TMA vacuum-sintered bodies are promising biomaterials for use as artificial bone materials to regenerate bone parts and produce bone reinforcement structures that are used for bone junctions in dental and orthopedic surgery.

Bone histology in extant and fossil penguins (Aves: Sphenisciformes).

PubMed

Ksepka, Daniel T; Werning, Sarah; Sclafani, Michelle; Boles, Zachary M

2015-11-01

Substantial changes in bone histology accompany the secondary adaptation to life in the water. This transition is well documented in several lineages of mammals and non-avian reptiles, but has received relatively little attention in birds. This study presents new observations on the long bone microstructure of penguins, based on histological sections from two extant taxa (Spheniscus and Aptenodytes) and eight fossil specimens belonging to stem lineages (†Palaeospheniscus and several indeterminate Eocene taxa). High bone density in penguins results from compaction of the internal cortical tissues, and thus penguin bones are best considered osteosclerotic rather than pachyostotic. Although the oldest specimens sampled in this study represent stages of penguin evolution that occurred at least 25 million years after the loss of flight, major differences in humeral structure were observed between these Eocene stem taxa and extant taxa. This indicates that the modification of flipper bone microstructure continued long after the initial loss of flight in penguins. It is proposed that two key transitions occurred during the shift from the typical hollow avian humerus to the dense osteosclerotic humerus in penguins. First, a reduction of the medullary cavity occurred due to a decrease in the amount of perimedullary osteoclastic activity. Second, a more solid cortex was achieved by compaction. In extant penguins and †Palaeospheniscus, most of the inner cortex is formed by rapid osteogenesis, resulting an initial latticework of woven-fibered bone. Subsequently, open spaces are filled by slower, centripetal deposition of parallel-fibered bone. Eocene stem penguins formed the initial latticework, but the subsequent round of compaction was less complete, and thus open spaces remained in the adult bone. In contrast to the humerus, hindlimb bones from Eocene stem penguins had smaller medullary cavities and thus higher compactness values compared with extant taxa. Although cortical lines of arrested growth have been observed in extant penguins, none was observed in any of the current sampled specimens. Therefore, it is likely that even these 'giant' penguin taxa completed their growth cycle without a major pause in bone deposition, implying that they did not undergo a prolonged fasting interval before reaching adult size. © 2015 Anatomical Society.

Bone histology in extant and fossil penguins (Aves: Sphenisciformes)

PubMed Central

Ksepka, Daniel T; Werning, Sarah; Sclafani, Michelle; Boles, Zachary M

2015-01-01

Substantial changes in bone histology accompany the secondary adaptation to life in the water. This transition is well documented in several lineages of mammals and non-avian reptiles, but has received relatively little attention in birds. This study presents new observations on the long bone microstructure of penguins, based on histological sections from two extant taxa (Spheniscus and Aptenodytes) and eight fossil specimens belonging to stem lineages (†Palaeospheniscus and several indeterminate Eocene taxa). High bone density in penguins results from compaction of the internal cortical tissues, and thus penguin bones are best considered osteosclerotic rather than pachyostotic. Although the oldest specimens sampled in this study represent stages of penguin evolution that occurred at least 25 million years after the loss of flight, major differences in humeral structure were observed between these Eocene stem taxa and extant taxa. This indicates that the modification of flipper bone microstructure continued long after the initial loss of flight in penguins. It is proposed that two key transitions occurred during the shift from the typical hollow avian humerus to the dense osteosclerotic humerus in penguins. First, a reduction of the medullary cavity occurred due to a decrease in the amount of perimedullary osteoclastic activity. Second, a more solid cortex was achieved by compaction. In extant penguins and †Palaeospheniscus, most of the inner cortex is formed by rapid osteogenesis, resulting an initial latticework of woven-fibered bone. Subsequently, open spaces are filled by slower, centripetal deposition of parallel-fibered bone. Eocene stem penguins formed the initial latticework, but the subsequent round of compaction was less complete, and thus open spaces remained in the adult bone. In contrast to the humerus, hindlimb bones from Eocene stem penguins had smaller medullary cavities and thus higher compactness values compared with extant taxa. Although cortical lines of arrested growth have been observed in extant penguins, none was observed in any of the current sampled specimens. Therefore, it is likely that even these ‘giant’ penguin taxa completed their growth cycle without a major pause in bone deposition, implying that they did not undergo a prolonged fasting interval before reaching adult size. PMID:26360700

Quantitative analysis on orientation of human bone integrated with midpalatal implant by micro X-ray diffractometer

NASA Astrophysics Data System (ADS)

Murata, Masaru; Akazawa, Toshiyuki; Yuasa, Toshihiro; Okayama, Miki; Tazaki, Junichi; Hanawa, Takao; Arisue, Makoto; Mizoguchi, Itaru

2012-12-01

A midpalatal implant system has been used as the unmoved anchorage for teeth movement. An 18-year-old male patient presented with reversed occlusion and was diagnosed as malocclusion. A pure titanium fixture (lengths: 4 mm, diameter: 3.3 mm, Orthosystem®, Institute Straumann, Switzerland) was implanted into the palatal bone of the patient as the orthodontic anchorage. The implant anchorage was connected with the upper left and right first molars, and had been used for 3 years. After dynamic treatments, the titanium fixture connected with bone was removed surgically, fixed in formalin solution, and embedded in resin. Specimens were cut along the frontal section of face and the direction of longitudinal axis of the implant, stained, and observed histologically. The titanium fixture was integrated directly with compact bone showing cortical bone-like structure such as lamella and osteon. In addition, to qualitatively characterize the implant-supported human bone, the crystallinity and orientation of hydroxyapatite (HAp) phase were evaluated by the microbeam X-ray diffraction analysis. Preferential alignment of c-axis of HAp crystals was represented by the relative intensity ratio of (0 0 2)-face diffraction peak to (3 1 0)-face one. The values decreased monotonously along the direction of the lateral stress from the site near the implant thread to the distant site in all horizontal lines of the map. These results indicated that the X-ray images for the intensity of c-face in HAp revealed functionally graded distribution of cortical bone quality. The micro-scale measurements of HAp structure could be a useful method for evaluating the mechanical stress distribution in human hard tissues.

DNA survival and physical and histological properties of heat-induced alterations in burnt bones.

PubMed

Imaizumi, K; Taniguchi, K; Ogawa, Y

2014-05-01

During forensic casework, it is vital to be able to obtain valuable information from burnt bone fragments to ascertain the identity of the victim. Here, we report the findings of an experimental study on burnt bovine compact bone segments. Compact bones were cut to size and heated in an electric furnace at a temperature range of 100–1,100 °C with 100 °C increments. Heat-induced alterations to the bone color,weight, volume, and density were monitored using gross morphology and micro-focus X-ray computed tomography.We found that the increase in temperature caused the color of the compact bones to change in order of yellow, brown, gray,and white. In contrast to the weight reduction that occurred immediately after burning, we measured no significant reduction in volume even at 600 °C; however, volume reduced drastically once the temperature reached 700 °C. Light microscopic histological observations of burnt bone revealed heat induced alterations such as cracking and separation of the osteons at higher temperatures. In addition to these findings,we sought to examine the survival of DNA in the burnt bones using polymerase chain reaction of mitochondrial DNA. No amplification was found in the specimens burnt at 250 °C or higher, indicating the likely difficulty in testing the DNA of burnt bones from forensic casework. The results of this study will enable an estimation of the burning temperatures of burnt bones found in forensic cases and will provide an important framework with which to interpret data obtained during anthropological testing and DNA typing.

Development and initial validation of a novel smoothed-particle hydrodynamics-based simulation model of trabecular bone penetration by metallic implants.

PubMed

Kulper, Sloan A; Fang, Christian X; Ren, Xiaodan; Guo, Margaret; Sze, Kam Y; Leung, Frankie K L; Lu, William W

2018-04-01

A novel computational model of implant migration in trabecular bone was developed using smoothed-particle hydrodynamics (SPH), and an initial validation was performed via correlation with experimental data. Six fresh-frozen human cadaveric specimens measuring 10 × 10 × 20 mm were extracted from the proximal femurs of female donors (mean age of 82 years, range 75-90, BV/TV ratios between 17.88% and 30.49%). These specimens were then penetrated under axial loading to a depth of 10 mm with 5 mm diameter cylindrical indenters bearing either flat or sharp/conical tip designs similar to blunt and self-tapping cancellous screws, assigned in a random manner. SPH models were constructed based on microCT scans (17.33 µm) of the cadaveric specimens. Two initial specimens were used for calibration of material model parameters. The remaining four specimens were then simulated in silico using identical material model parameters. Peak forces varied between 92.0 and 365.0 N in the experiments, and 115.5-352.2 N in the SPH simulations. The concordance correlation coefficient between experimental and simulated pairs was 0.888, with a 95%CI of 0.8832-0.8926, a Pearson ρ (precision) value of 0.9396, and a bias correction factor Cb (accuracy) value of 0.945. Patterns of bone compaction were qualitatively similar; both experimental and simulated flat-tipped indenters produced dense regions of compacted material adjacent to the advancing face of the indenter, while sharp-tipped indenters deposited compacted material along their peripheries. Simulations based on SPH can produce accurate predictions of trabecular bone penetration that are useful for characterizing implant performance under high-strain loading conditions. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1114-1123, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Induction and quantification of collagen fiber alignment in a three-dimensional hydroxyapatite-collagen composite scaffold.

PubMed

Banglmaier, Richard F; Sander, Edward A; VandeVord, Pamela J

2015-04-01

Hydroxyapatite-collagen composite scaffolds are designed to serve as a regenerative load bearing replacement that mimics bone. However, the material properties of these scaffolds are at least an order of magnitude less than that of bone and subject to fail under physiological loading conditions. These scaffolds compositionally resemble bone but they do not possess important structural attributes such as an ordered arrangement of collagen fibers, which is a correlate to the mechanical properties in bone. Furthermore, it is unclear how much ordering of structure is satisfactory to mimic bone. Therefore, quantitative methods are needed to characterize collagen fiber alignment in these scaffolds for better correlation between the scaffold structure and the mechanical properties. A combination of extrusion and compaction was used to induce collagen fiber alignment in composite scaffolds. Collagen fiber alignment, due to extrusion and compaction, was quantified from polarized light microscopy images with a Fourier transform image processing algorithm. The Fourier transform method was capable of resolving the degree of collagen alignment from polarized light images. Anisotropy indices of the image planes ranged from 0.08 to 0.45. Increases in the degree of fiber alignment induced solely by extrusion (0.08-0.25) or compaction (0.25-0.44) were not as great as those by the combination of extrusion and compaction (0.35-0.45). Additional measures of randomness and fiber direction corroborate these anisotropy findings. This increased degree of collagen fiber alignment was induced in a preferred direction that is consistent with the extrusion direction and parallel with the compacted plane. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Correlation between ultrasound velocity and densitometry in fresh and demineralized cortical bone

PubMed Central

de Mesquita, Alessandro Queiroz; Barbieri, Giuliano; Barbieri, Claudio Henrique

2016-01-01

OBJECTIVE: To compare ultrasound propagation velocity with densitometry in the diaphyseal compact cortical bone of whole sheep metatarsals. METHODS: The transverse ultrasound velocity and bone mineral density of 5-cm-long diaphyseal bone segments were first measured. The bone segments were then divided into four groups of 15 segments each and demineralized in an aqueous 0.5 N hydrochloric acid solution for 6, 12, 24 or 36 hours. All measurements were repeated after demineralization for each time duration and the values measured before and after demineralization were compared. RESULTS: Ultrasound velocity and bone mineral density decreased with demineralization time, and most differences in the pre- and post-demineralization values within each group and between groups were significant: A moderate correlation coefficient (r=0.75956) together with a moderate agreement was determined between both post-demineralization parameters, detected by the Bland-Altman method. CONCLUSION: We conclude that both ultrasound velocity and bone mineral density decrease as a result of demineralization, thus indicating that bone mineral content is of great importance for maintaining the acoustic parameters of cortical bone, as observed for cancellous bone. Ultrasound velocity can be used to evaluate both compact cortical bone quality and bone mineral density. PMID:27982167

Correlation between ultrasound velocity and densitometry in fresh and demineralized cortical bone.

PubMed

Mesquita, Alessandro Queiroz de; Barbieri, Giuliano; Barbieri, Claudio Henrique

2016-11-01

To compare ultrasound propagation velocity with densitometry in the diaphyseal compact cortical bone of whole sheep metatarsals. The transverse ultrasound velocity and bone mineral density of 5-cm-long diaphyseal bone segments were first measured. The bone segments were then divided into four groups of 15 segments each and demineralized in an aqueous 0.5 N hydrochloric acid solution for 6, 12, 24 or 36 hours. All measurements were repeated after demineralization for each time duration and the values measured before and after demineralization were compared. Ultrasound velocity and bone mineral density decreased with demineralization time, and most differences in the pre- and post-demineralization values within each group and between groups were significant: A moderate correlation coefficient (r=0.75956) together with a moderate agreement was determined between both post-demineralization parameters, detected by the Bland-Altman method. We conclude that both ultrasound velocity and bone mineral density decrease as a result of demineralization, thus indicating that bone mineral content is of great importance for maintaining the acoustic parameters of cortical bone, as observed for cancellous bone. Ultrasound velocity can be used to evaluate both compact cortical bone quality and bone mineral density.

Strontium transfer from maternal skeleton to the fetus estimated on the basis of the Techa river data

NASA Technical Reports Server (NTRS)

Tolstykh, E. I.; Degteva, M. O.; Kozheurov, V. P.; Burmistrov, D. S.; Neta, R. (Principal Investigator)

1998-01-01

Measurements of 90Sr in human bone of inhabitants of the Techa river region were started in 1951, and since 1974 the Techa river population has been studied with a whole-body counter. One of the dosimetric tasks that could be decided using data on 90Sr measurements is direct evaluation of strontium transfer to the fetus from the maternal skeleton. Six cases were selected for which 90Sr measurements were available both for stillborn infants and their mothers. The ratio of 90Sr concentrations in fetal bone to maternal bone for the year of pregnancy has been evaluated. Two clusters of values were found and the difference between clusters could be explained by age-dependent features of maternal bone formation and remodelling. When the mother's 90Sr intake occurred in the period of intensive compact bone growth, the transfer coefficient was very low (0.012-0.032). If 90Sr ingestion occurred during the woman's reproductive age, the transfer to fetus was equal to 0.21-0.26.

Osteal integration of porous implants from titanium nickelide.

PubMed

Kelmakov, V P; Itin, V I; Epifancev, A G; Lepakova, O K; Kitler, V D; Bulgakov, V N

2009-10-01

The microstructure of preparations from porous titanium nickelide was studied 4.5 months and 1.5 years after operations on the anterior compartments of the spine. Organic tissues of different morphology, compactness, and thickness occupied 100% of analyzed surface 1.5 years after implantation, while after 4.5 months the pores were filled by 60%. The content of calcium and phosphorus elements in surface pores after 1.5 years was close to their concentrations in human bones.

Preparation and characterization of a novel willemite bioceramic.

PubMed

Zhang, Meili; Zhai, Wanyin; Chang, Jiang

2010-04-01

Willemite (Zn(2)SiO(4)) ceramics were prepared by sintering the willemite green compacts. The effects of sintering temperature on the linear shrinkage, porosity and mechanical strength of the ceramics were examined. With the sintering temperature increased, the linear shrinkage of the ceramics increased and the porosity decreased. When sintered at 1,300 degrees C, willemite ceramics showed mechanical properties of the same order of magnitude as values for human cortical bone, as measured by bending strength (91.2 +/- 4.2 MPa) and Young's modulus (37.5 +/- 1.5 GPa). In addition, the adhesion and proliferation of rabbit bone marrow stromal cells (BMSCs) on willemite ceramics was investigated. The results showed that the ceramics supported cell adhesion and stimulated the proliferation. All these findings suggest that willemite ceramics possess suitable mechanical properties and favorable biocompatibility and might be a promising biomaterial for bone implant applications.

Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium phosphate induces osteon formation.

PubMed

Fernández, Tulio; Olave, Gilberto; Valencia, Carlos H; Arce, Sandra; Quinn, Julian M W; Thouas, George A; Chen, Qi-Zhi

2014-07-01

Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ∼60 μm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several μm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.

Collagen type XI alpha1 may be involved in the structural plasticity of the vertebral column in Atlantic salmon (Salmo salar L.).

PubMed

Wargelius, A; Fjelldal, P G; Nordgarden, U; Grini, A; Krossøy, C; Grotmol, S; Totland, G K; Hansen, T

2010-04-01

Atlantic salmon (Salmo salar L.) vertebral bone displays plasticity in structure, osteoid secretion and mineralization in response to photoperiod. Other properties of the vertebral bone, such as mineral content and mechanical strength, are also associated with common malformations in farmed Atlantic salmon. The biological mechanisms that underlie these changes in bone physiology are unknown, and in order to elucidate which factors might be involved in this process, microarray assays were performed on vertebral bone of Atlantic salmon reared under natural or continuous light. Eight genes were upregulated in response to continuous light treatment, whereas only one of them was upregulated in a duplicate experiment. The transcriptionally regulated gene was predicted to code for collagen type XI alpha1, a protein known to be involved in controlling the diameter of fibrillar collagens in mammals. Furthermore, the gene was highly expressed in the vertebrae, where spatial expression was found in trabecular and compact bone osteoblasts and in the chordoblasts of the notochordal sheath. When we measured the expression level of the gene in the tissue compartments of the vertebrae, the collagen turned out to be 150 and 25 times more highly expressed in the notochord and compact bone respectively, relative to the expression in the trabecular bone. Gene expression was induced in response to continuous light, and reduced in compressed vertebrae. The downregulation in compressed vertebrae was due to reduced expression in the compact bone, while expression in the trabecular bone and the notochord was unaffected. These data support the hypothesis that this gene codes for a presumptive collagen type XI alpha1, which may be involved in the regulatory pathway leading to structural adaptation of the vertebral architecture.

Bone structure of the temporo-mandibular joint in the individuals aged 18-25.

PubMed

Parafiniuk, M; Gutsch-Trepka, A; Trepka, S; Sycz, K; Wolski, S; Parafiniuk, W

1998-01-01

Osteohistometric studies were performed in 15 female and 15 male cadavers aged 18-25. Condyloid process and right and left acetabulum of the temporo-mandibular joint have been studied. Density has been investigated using monitor screen linked with microscope (magnification 80x). Density in the spongy part of the condyloid process was 26.67-26.77%; in the subchondrial layer--72.13-72.72%, and in the acetabular wall 75.03-75.91%. Microscopic structure of the bones of the temporo-mandibular joint revealed no differences when compared with images of compact and cancellous bone shown in the histology textbooks. Sex and the side of the body had no influence on microscopic image and proportional bone density. Isles of chondrocytes in the trabeculae of the spongy structure of the condyloid process were found in 4 cases and isles of the condensed bone resembling the compact pattern in 7 cases.

Bone-like apatite layer formation on hydroxyapatite prepared by spark plasma sintering (SPS).

PubMed

Gu, Y W; Khor, K A; Cheang, P

2004-08-01

Hydroxyapatite (HA) compacts with high density and superior mechanical properties were fabricated by spark plasma sintering (SPS) using spray-dried HA powders as feedstock. The formation of bone-like apatite layer on SPS consolidated HA compacts were investigated by soaking the HA compacts in simulated body fluid (SBF) for various periods (maximum of 28 days). The structural changes in HA post-SBF were analyzed with scanning electron microscopy, grazing incidence X-ray diffraction and X-ray photoelectron spectroscopy. It was found that a layer consisting microcrystalline carbonate-containing hydroxyapatite was formed on the surface of HA compacts after soaking for 24h. The formation mechanism of apatite on the surface of HA compacts after soaking in SBF was attributed to the ion exchange between HA compacts and the SBF solution. The increase in ionic concentration of calcium and phosphorus as well as the increase in pH after SBF immersion resulted in an increase in ionic activity product of apatite in the solution, and provided a specific surface with a low interface energy that is conducive to the nucleation of apatite on the surface of HA compacts.

Vascular Spaces in Compact Bone: A Technique to Correct a Common Misinterpretation of Structure

ERIC Educational Resources Information Center

Locke, M.; Dean, Rob L.

2003-01-01

Old bones are often discolored by the grime that infiltrates spaces in the matrix once occupied by blood vessels. This suggested that allowing dry bone to absorb colorants might be a useful way to show the three dimensional complexity of bone vascularization. The authors have developed a simple way to show blood vessels spaces in bone at a glance…

Histological Evidence of the Osseointegration of Fractured Direct Metal Laser Sintering Implants Retrieved after 5 Years of Function.

PubMed

Mangano, Francesco; Mangano, Carlo; Piattelli, Adriano; Iezzi, Giovanna

2017-01-01

Direct metal laser sintering (DMLS) is an additive manufacturing technique that allows the fabrication of dental implants layer by layer through the laser fusion of titanium microparticles. The surface of DMLS implants is characterized by a high open porosity with interconnected pores of different sizes; therefore, it has the potential to enhance and accelerate bone healing. To date, however, there are no histologic/histomorphometric studies in the literature evaluating the interface between bone and DMLS implants in the long-term. To evaluate the interface between bone and DMLS implants retrieved after 5 years of functional loading. Two fractured DMLS implants were retrieved from the human jaws, using a 5 mm trephine bur. Both the implants were clinically stable and functioned regularly before fracture. The specimens were processed for histologic/histomorphometric evaluation; the bone-to-implant contact (BIC%) was calculated. Compact, mature lamellar bone was found over most of the DMLS implants in close contact with the implant surface; the histomorphometric evaluation showed a mean BIC% of 66.1% (±4.5%). The present histologic/histomorphometric study showed that DMLS implants were well integrated in bone, after 5 years of loading, with the peri-implant bone undergoing continuous remodeling at the interface.

Histological Evidence of the Osseointegration of Fractured Direct Metal Laser Sintering Implants Retrieved after 5 Years of Function

PubMed Central

Piattelli, Adriano

2017-01-01

Background Direct metal laser sintering (DMLS) is an additive manufacturing technique that allows the fabrication of dental implants layer by layer through the laser fusion of titanium microparticles. The surface of DMLS implants is characterized by a high open porosity with interconnected pores of different sizes; therefore, it has the potential to enhance and accelerate bone healing. To date, however, there are no histologic/histomorphometric studies in the literature evaluating the interface between bone and DMLS implants in the long-term. Purpose To evaluate the interface between bone and DMLS implants retrieved after 5 years of functional loading. Methods Two fractured DMLS implants were retrieved from the human jaws, using a 5 mm trephine bur. Both the implants were clinically stable and functioned regularly before fracture. The specimens were processed for histologic/histomorphometric evaluation; the bone-to-implant contact (BIC%) was calculated. Results Compact, mature lamellar bone was found over most of the DMLS implants in close contact with the implant surface; the histomorphometric evaluation showed a mean BIC% of 66.1% (±4.5%). Conclusions The present histologic/histomorphometric study showed that DMLS implants were well integrated in bone, after 5 years of loading, with the peri-implant bone undergoing continuous remodeling at the interface. PMID:28929117

Growth differentiation factor‑5 induces tenomodulin expression via phosphorylation of p38 and promotes viability of murine mesenchymal stem cells from compact bone.

PubMed

Qu, Yanlong; Zhou, Li; Lv, Bing; Wang, Chunlei; Li, Pengwei

2018-03-01

Growth differentiation factor (GDF)‑5 serves a role in tissue development and tenomodulin serves an important role in the development of tendons. The effects of GDF‑5 on mesenchymal stem cells (MSCs), particularly with regards to tendon bioengineering, are poorly understood. The present study aimed to investigate the effects of GDF‑5 on cell viability and tenomodulin expression in MSCs from murine compact bone. MSCs were isolated from murine compact bones and confirmed by flow cytometric analysis. In addition, the adipogenic, osteoblastic and chondrocyte differentiation capabilities of the MSCs were determined. MSCs were treated with GDF‑5 and the effects of GDF‑5 on MSC viability were determined. The mRNA and protein expression levels of tenomodulin were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. MSCs from murine compact bone were successfully isolated. GDF‑5 had optimal effects on cell viability at 100 ng/ml (+36.9% of control group without GDF‑5 treatment, P<0.01) and its effects peaked after 6 days of treatment (+56.6% of control group, P<0.001). Compared with the control group, treatment with 100 ng/ml GDF‑5 for 4 days enhanced the mRNA expression levels of tenomodulin (3.56±0.94 vs. 1.02±0.25; P<0.05). In addition, p38 was activated by GDF‑5, as determined by enhanced expression levels of phosphorylated p38 (p‑p38). The GDF‑5‑induced protein expression levels of p‑p38 and tenomodulin were markedly inhibited following treatment with SB203580, an inhibitor of p38 mitogen‑activated protein kinase. These results suggested that GDF‑5 treatment may increase tenomodulin protein expression via phosphorylation of p38 in MSCs from murine compact bone. These findings may aid the future development of tendon bioengineering.

Statistical shape analysis of clavicular cortical bone with applications to the development of mean and boundary shape models.

PubMed

Lu, Yuan-Chiao; Untaroiu, Costin D

2013-09-01

During car collisions, the shoulder belt exposes the occupant's clavicle to large loading conditions which often leads to a bone fracture. To better understand the geometric variability of clavicular cortical bone which may influence its injury tolerance, twenty human clavicles were evaluated using statistical shape analysis. The interior and exterior clavicular cortical bone surfaces were reconstructed from CT-scan images. Registration between one selected template and the remaining 19 clavicle models was conducted to remove translation and rotation differences. The correspondences of landmarks between the models were then established using coordinates and surface normals. Three registration methods were compared: the LM-ICP method; the global method; and the SHREC method. The LM-ICP registration method showed better performance than the global and SHREC registration methods, in terms of compactness, generalization, and specificity. The first four principal components obtained by using the LM-ICP registration method account for 61% and 67% of the overall anatomical variation for the exterior and interior cortical bone shapes, respectively. The length was found to be the most significant variation mode of the human clavicle. The mean and two boundary shape models were created using the four most significant principal components to investigate the size and shape variation of clavicular cortical bone. In the future, boundary shape models could be used to develop probabilistic finite element models which may help to better understand the variability in biomechanical responses and injuries to the clavicle. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Electron Microscopy and Analytical X-ray Characterization of Compositional and Nanoscale Structural Changes in Fossil Bone

NASA Astrophysics Data System (ADS)

Boatman, Elizabeth Marie

The nanoscale structure of compact bone contains several features that are direct indicators of bulk tissue mechanical properties. Fossil bone tissues represent unique opportunities to understand the compact bone structure/property relationships from a deep time perspective, offering a possible array of new insights into bone diseases, biomimicry of composite materials, and basic knowledge of bioapatite composition and nanoscale bone structure. To date, most work with fossil bone has employed microscale techniques and has counter-indicated the survival of bioapatite and other nanoscale structural features. The obvious disconnect between the use of microscale techniques and the discernment of nanoscale structure has prompted this work. The goal of this study was to characterize the nanoscale constituents of fossil compact bone by applying a suite of diffraction, microscopy, and spectrometry techniques, representing the highest levels of spatial and energy resolution available today, and capable of complementary structural and compositional characterization from the micro- to the nanoscale. Fossil dinosaur and crocodile long bone specimens, as well as modern ratite and crocodile femurs, were acquired from the UC Museum of Paleontology. Preserved physiological features of significance were documented with scanning electron microscopy back-scattered imaging. Electron microprobe wavelength-dispersive X-ray spectroscopy (WDS) revealed fossil bone compositions enriched in fluorine with a complementary loss of oxygen. X-ray diffraction analyses demonstrated that all specimens were composed of apatite. Transmission electron microscopy (TEM) imaging revealed preserved nanocrystallinity in the fossil bones and electron diffraction studies further identified these nanocrystallites as apatite. Tomographic analyses of nanoscale elements imaged by TEM and small angle X-ray scattering were performed, with the results of each analysis further indicating that nanoscale structure is highly conserved in these four fossil specimens. Finally, the results of this study indicate that bioapatite can be preserved in even the most ancient vertebrate specimens, further supporting the idea that fossilization is a preservational process. This work also underlines the importance of using appropriately selected characterization and analytical techniques for the study of fossil bone, especially from the perspective of spatial resolution and the scale of the bone structural features in question.

Gelatine modified monetite as a bone substitute material: An in vitro assessment of bone biocompatibility.

PubMed

Kruppke, Benjamin; Farack, Jana; Wagner, Alena-Svenja; Beckmann, Sarah; Heinemann, Christiane; Glenske, Kristina; Rößler, Sina; Wiesmann, Hans-Peter; Wenisch, Sabine; Hanke, Thomas

2016-03-01

Calcium phosphate phases are increasingly used for bone tissue substitution, and the load bearing properties of these inherently brittle biomaterials are increased by inclusion of organic components. Monetite prepared using mineralization of gelatine pre-structured through phosphate leads to a significantly increased biaxial strength and indirect tensile strength compared to gelatine-free monetite. Besides the mechanical properties, degradation in physiological solutions and osteoblast and osteoclast cell response were investigated. Human bone marrow stromal cells (hBMSCs) showed considerably higher proliferation rates on the gelatine modified monetite than on polystyrene reference material in calcium-free as well as standard cell culture medium (α-MEM). Osteogenic differentiation on the material was comparable to polystyrene in both medium types. Osteoclast-like cells derived from monocytes were able to actively resorb the biomaterial. Osteoblastic differentiation and perhaps even more important the cellular resorption of the biomaterial indicate that it can be actively involved in the bone remodeling process. Thus the behavior of osteoblasts and osteoclasts as well as the adequate degradation and mechanical properties are strong indicators for bone biocompatibility, although in vivo studies are still required to prove this. New and unique? A low temperature precipitationprocessforcalcium anhydrous hydrogen phosphateallows for the first time to produce monolithic compact composites of monetite and gelatine. The composite is degradable and resorbable. To prove that, the question arises: what is bone biocompatibility? The reaction of both mayor cell types of bone represents this biocompatibility. Therefore, human bone marrow stromal cells were seeded revealing the materials pro-osteogenic properties. Monocyte cultivation, becoming recently focus of interest, revealed the capability of the biomaterial to be actively resorbed by derived osteoclast-like cells. Not new but necessary ismechanical characterization, which is often only investigated as uniaxial property. Here, a biaxial method is applied, to characterize the materials properties closer to its application loads. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[Preliminary result of allogenic bone and autogeneic-iliac bone in comminuted fracture reparation in rabbits].

PubMed

Wang, Zhi-qiang; Li, Qi-jia; Wang, Qi

2002-11-01

To observe the difference of the fracture reparation using autogeneic-iliac bone and allogenic bone. Comminuted fracture of humerus in two sides were made in rabbits. Autogeneic-iliac bone was implanted in one side, while allogenic bone of equal capacity was implanted in the other side. General observation, X-ray, and HE histologic section were done when the rabbits were put to death in different stages. One week after implantation, the graft had been enclosed by connective tissue without infiltration of the inflammatory cells. At the 2nd week, the graft had been enclosed in osteoplastic granulation tissue, and the cartilage callus had formed. At the 3rd week, there had been broken sequestrum among the callus; the cartilage had actively formed the bone; and the medulla had been making. At the 4th week, the sequestrum had disappeared, and the mature callus had appeared; the osteoblasts had arranged in a line around the edge of the mature callus. At the 5th week, the callus was strong, compact and approached mature bones. At the 6th week, there had been the compact lamellar structures and the complete haversian's systems. There was no significant difference between callus of two sides by using image quantitative analysis in the 3rd, 4th week (P > 0.05). The allogenic bone has good histocompatibility and bone conduction effect, and can be used for bone transplantation substitute with autogenous-iliac bone.

Synthesis and characterization of Ti-Ta-Nb-Mn foams.

PubMed

Aguilar, C; Guerra, C; Lascano, S; Guzman, D; Rojas, P A; Thirumurugan, M; Bejar, L; Medina, A

2016-01-01

The unprecedented increase in human life expectancy have produced profound changes in the prevailing patterns of disease, like the observed increased in degenerative disc diseases, which cause degradation of the bones. Ti-Nb-Ta alloys are promising materials to replace the damaged bone due to their excellent mechanical and corrosion resistance properties. In general metallic foams are widely used for medical application due to their lower elastic moduli compare to bulk materials. In this work we studied the synthesis of 34Nb-29Ta-xMn (x: 2, 4 and 6 wt.% Mn) alloy foams (50% v/v) using ammonium hydrogen carbonate as a space holder. Alloys were produced through mechanical alloying in a planetary mill for 50h. Green compacts were obtained by applying 430 MPa pressure. To remove the space holder from the matrix the green compacts were heated to 180 °C for 1.5h and after sintered at 1300 °C for 3h. Foams were characterized by x-ray diffraction, scanning, transmission electron microscopy and optical microscopy. The elastic modulus of the foam was measured as ~30 GPa, and the values are almost equal to the values predicted using various theoretical models. Copyright © 2015 Elsevier B.V. All rights reserved.

Study of the suitability of a commercial hydroxyapatite powder to obtain sintered compacts for medical applications

NASA Astrophysics Data System (ADS)

Palacio, C.; Jaramillo, D.; Correa, S.; Arroyave, M.

2017-06-01

Hydroxyapatite (HA) is a material widely used by the medical community due to its Ca/P ratio is comparable to the Ca/P ratio of bones and teeth, which promotes osteoinduction and osteoconduction processes when in contact with bone tissue, either as volume piece or coating. This work focuses on studying the quality of the commercial HA powder MKnano-#MKN-HXAP-S12 µm, after processing, to obtain sintered compact discs with suitable physical and chemical characteristics for implants applications. The HA powder was processed through calcination, grinding, pressing and sintering to evaluate the effect of such as procedures in the compacts dics quality. The raw powder was characterized by laser diffraction, SEM, XRF, XRD, TGA and DSC while the characteristics of the obtained compact discs were determined by dilatometry and XRD to identify the sintering temperature range, constituent phases, the amorphous content and the crystallinity degree, parameters that allow determining their suitability for implants applications. Although, it was not possible to obtain sintered compacts with the suitable chemical composition and without fractures, this work allowed to identify the parameters that determine the suitability of a HA powder to obtain sintered compacts for medical applications, as well as the characterization protocol that allows the evaluation of such parameters.

A compact in vivo neutron activation analysis system to quantify manganese in human hand bone

NASA Astrophysics Data System (ADS)

Liu, Yingzi

As an urgent issue of correlating cumulative manganese (Mn) exposure to neurotoxicity, bone has emerged as an attractive biomarker for long-term Mn deposition and storage. A novel Deuterium-Deuterium (DD) neutron generator irradiation system has been simulated and constructed, incorporating moderator, reflector and shielding. This neutron activation analysis (NAA) irradiation assembly presents several desirable features, including high neutron flux, improved detection limit and acceptable neutron & photon dose, which would allow it be ready for clinical measurement. Key steps include simulation modeling and verifying, irradiation system design, detector characterization, and neutron flux and dose assessment. Activation foils were also analyzed to reveal the accurate neutron spectrum in the irradiation cave. The detection limit with this system is 0.428 ppm with 36 mSv equivalent hand dose and 52 microSv whole body effective dose.

Fabrication of porous titanium scaffold materials by a fugitive filler method.

PubMed

Hong, T F; Guo, Z X; Yang, R

2008-12-01

A clean powder metallurgy route was developed here to produce Ti foams, using a fugitive polymeric filler, polypropylene carbonate (PPC), to create porosities in a metal-polymer compact at the pre-processing stage. The as-produced foams were studied by scanning electron microscopy (SEM), LECO combustion analyses and X-ray diffraction (XRD). Compression tests were performed to assess their mechanical properties. The results show that titanium foams with open pores can be successfully produced by the method. The compressive strength and modulus of the foams decrease with an increasing level of porosity and can be tailored to those of the human bones. After alkali treatment and soaking in a simulated body fluid (SBF) for 3 days, a thin apatite layer was formed along the Ti foam surfaces, which provides favourable bioactive conditions for bone bonding and growth.

Trace elements distribution and post-mortem intake in human bones from Middle Age by total reflection X-ray fluorescence*1

NASA Astrophysics Data System (ADS)

Carvalho, M. L.; Marques, A. F.; Lima, M. T.; Reus, U.

2004-08-01

The purpose of the present work is to investigate the suitability of TXRF technique to study the distribution of trace elements along human bones of the 13th century, to conclude about environmental conditions and dietary habits of old populations and to study the uptake of some elements from the surrounding soil. In this work, we used TXRF to quantify and to make profiles of the elements through long bones. Two femur bones, one from a man and another from a woman, buried in the same grave were cross-sectioned in four different points at a distance of 1 cm. Microsamples of each section were taken at a distance of 1 mm from each other. Quantitative analysis was performed for Ca, Mn, Fe, Cu, Zn, Sr, Ba and Pb. Very high concentrations of Mn and Fe were obtained in the whole analysed samples, reaching values higher than 2% in some samples of trabecular tissue, very much alike to the concentrations in the burial soil. A sharp decrease for both elements was observed in cortical tissue. Zn and Sr present steady concentration levels in both kinds of bone tissues. Pb and Cu show very low concentrations in the inner tissue of cortical bone. However, these concentrations increase in the regions in contact to trabecular tissue and external surface in contact with the soil, where high levels of both elements were found. We suggest that contamination from the surrounding soil exists for Mn and Fe in the whole bone tissue. Pb can be both from post-mortem and ante-mortem origin. Inner compact tissue might represent in vivo accumulation and trabecular one corresponds to uptake during burial. The steady levels of Sr and Zn together with soil concentration lower levels for these elements may allow us to conclude that they are originated from in vivo incorporation in the hydroxyapatite bone matrix.

Compaction dynamics of crunchy granular material

NASA Astrophysics Data System (ADS)

Guillard, François; Golshan, Pouya; Shen, Luming; Valdès, Julio R.; Einav, Itai

2017-06-01

Compaction of brittle porous material leads to a wide variety of densification patterns. Static compaction bands occurs naturally in rocks or bones, and have important consequences in industry for the manufacturing of powder tablets or metallic foams for example. Recently, oscillatory compaction bands have been observed in brittle porous media like snow or cereals. We will discuss the great variety of densification patterns arising during the compaction of puffed rice, including erratic compaction at low velocity, one or several travelling compaction bands at medium velocity and homogeneous compaction at larger velocity. The conditions of existence of each pattern are studied thanks to a numerical spring lattice model undergoing breakage and is mapped to the phase diagram of the patterns based on dimensionless characteristic quantities. This also allows to rationalise the evolution of the compaction behaviour during a single test. Finally, the localisation of compaction bands is linked to the strain rate sensitivity of the material.

A compact DD neutron generator-based NAA system to quantify manganese (Mn) in bone in vivo.

PubMed

Liu, Yingzi; Byrne, Patrick; Wang, Haoyu; Koltick, David; Zheng, Wei; Nie, Linda H

2014-09-01

A deuterium-deuterium (DD) neutron generator-based neutron activation analysis (NAA) system has been developed to quantify metals, including manganese (Mn), in bone in vivo. A DD neutron generator with a flux of up to 3*10(9) neutrons s(-1) was set up in our lab for this purpose. Optimized settings, including moderator, reflector, and shielding material and thickness, were selected based on Monte Carlo (MC) simulations conducted in our previous work. Hand phantoms doped with different Mn concentrations were irradiated using the optimized DD neutron generator irradiation system. The Mn characteristic γ-rays were collected by an HPGe detector system with 100% relative efficiency. The calibration line of the Mn/calcium (Ca) count ratio versus bone Mn concentration was obtained (R(2) = 0.99) using the hand phantoms. The detection limit (DL) was calculated to be about 1.05 μg g(-1) dry bone (ppm) with an equivalent dose of 85.4 mSv to the hand. The DL can be reduced to 0.74 ppm by using two 100% HPGe detectors. The whole body effective dose delivered to the irradiated subject was calculated to be about 17 μSv. Given the average normal bone Mn concentration of 1 ppm in the general population, this system is promising for in vivo bone Mn quantification in humans.

Application of fracture mechanics to failure in manatee rib bone.

PubMed

Yan, Jiahau; Clifton, Kari B; Reep, Roger L; Mecholsky, John J

2006-06-01

The Florida manatee (Trichechus manatus latirostris) is listed as endangered by the U.S. Department of the Interior. Manatee ribs have different microstructure from the compact bone of other mammals. Biomechanical properties of the manatee ribs need to be better understood. Fracture toughness (K(C)) has been shown to be a good index to assess the mechanical performance of bone. Quantitative fractography can be used in concert with fracture mechanics equations to identify fracture initiating defects/cracks and to calculate the fracture toughness of bone materials. Fractography is a standard technique for analyzing fracture behavior of brittle and quasi-brittle materials. Manatee ribs are highly mineralized and fracture in a manner similar to quasi-brittle materials. Therefore, quantitative fractography was applied to determine the fracture toughness of manatee ribs. Average fracture toughness values of small flexure specimens from six different sizes of manatees ranged from 1.3 to 2.6 MPa(m)(12). Scanning electron microscope (SEM) images show most of the fracture origins were at openings for blood vessels and interlayer spaces. Quantitative fractography and fracture mechanics can be combined to estimate the fracture toughness of the material in manatee rib bone. Fracture toughness of subadult and calf manatees appears to increase as the size of the manatee increases. Average fracture toughness of the manatee rib bone materials is less than the transverse fracture toughness of human and bovine tibia and femur.

Response of human bone marrow-derived MSCs on triphasic Ca-P substrate with various HA/TCP ratio.

PubMed

Bajpai, Indu; Kim, Duk Yeon; Kyong-Jin, Jung; Song, In-Hwan; Kim, Sukyoung

2017-01-01

Calcium phosphates (Ca-P) are used commonly as artificial bone substitutes to control the biodegradation rate of an implant in the body fluid. This study examined the in vitro proliferation of human bone marrow-derived mesenchymal stem cells (hBMSCs) on triphasic Ca-P samples. For this aspect, hydroxyapatite (HA), dicalcium phosphate dehydrate (DCPD), and calcium hydroxide (Ca(OH) 2 ) were mixed at various ratios, cold compacted, and sintered at 1250°C in air. X-ray diffraction showed that the β-tricalcium phosphate (TCP) to α-TCP phase transformation increased with increasing DCPD/HA ratio. The micro-hardness deceased with increasing TCP content, whereas the mean grain size and porosity increased with increasing TCP concentration. To evaluate the in vitro degree of adhesion and proliferation on the HA/TCP samples, human BMSCs were incubated on the HA/TCP samples and analyzed by a cells proliferation assay, expression of the extracellular matrix (ECM) genes, such as α-smooth muscle actin (α-SMA) and fibronectin (FN), and FITC-phalloidin fluorescent staining. In terms of the interactions of human BMSCs with the triphasic Ca-P samples, H50T50 (Ca/P = 1.59) markedly enhanced cell spreading, proliferation, FN, and α-SMA compared with H100T0 (Ca/P = 1.67). Interestingly, these results show that among the five HA/TCP samples, H50T50 is the optimal Ca-P composition for in vitro cell proliferation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 72-80, 2017. © 2015 Wiley Periodicals, Inc.

[Scanning electron microscopy of heat-damaged bone tissue].

PubMed

Harsanyl, L

1977-02-01

Parts of diaphyses of bones were exposed to high temperature of 200-1300 degrees C. Damage to the bone tissue caused by the heat was investigated. The scanning electron microscopic picture seems to be characteristic of the temperature applied. When the bones heated to the high temperature of 700 degrees C characteristic changes appear on the periostal surface, higher temperatura on the other hand causes damage to the compact bone tissue and can be observed on the fracture-surface. Author stresses the importance of this technique in the legal medicine and anthropology.

Mandibular bone changes in 24 years and skeletal fracture prediction.

PubMed

Jonasson, G; Sundh, V; Hakeberg, M; Hassani-Nejad, A; Lissner, L; Ahlqwist, M

2013-03-01

The objectives of the investigation were to describe changes in mandibular bone structure with aging and to compare the usefulness of cortical and trabecular bone for fracture prediction. From 1968 to 1993, 1,003 women were examined. With the help of panoramic radiographs, cortex thickness was measured and cortex was categorized as: normal, moderately, or severely eroded. The trabeculation was assessed as sparse, mixed, or dense. Visually, the mandibular compact and trabecular bone transformed gradually during the 24 years. The compact bone became more porous, the intertrabecular spaces increased, and the radiographic image of the trabeculae seemed less mineralized. Cortex thickness increased up to the age of 50 and decreased significantly thereafter. At all examinations, the sparse trabeculation group had more fractures (71-78 %) than the non-sparse group (27-31 %), whereas the severely eroded compact group showed more fractures than the less eroded groups only in 1992/1993, 24 years later. Sparse trabecular pattern was associated with future fractures both in perimenopausal and older women (relative risk (RR), 1.47-4.37) and cortical erosion in older women (RR, 1.35-1.55). RR for future fracture associated with a severely eroded cortex increased to 4.98 for cohort 1930 in 1992/1993. RR for future fracture associated with sparse trabeculation increased to 11.43 for cohort 1922 in 1992/1993. Dental radiographs contain enough information to identify women most at risk of future fracture. When observing sparse mandibular trabeculation, dentists can identify 40-69 % of women at risk for future fractures, depending on participant age at examination.

Biomimetics of Bone Implants: The Regenerative Road.

PubMed

Brett, Elizabeth; Flacco, John; Blackshear, Charles; Longaker, Michael T; Wan, Derrick C

2017-01-01

The current strategies for healing bone defects are numerous and varied. At the core of each bone healing therapy is a biomimetic mechanism, which works to enhance bone growth. These range from porous scaffolds, bone mineral usage, collagen, and glycosaminoglycan substitutes to transplanted cell populations. Bone defects face a range of difficulty in their healing, given the composite of dense outer compact bone and blood-rich inner trabecular bone. As such, the tissue possesses a number of inherent characteristics, which may be clinically harnessed as promoters of bone healing. These include mechanical characteristics, mineral composition, native collagen content, and cellular fraction of bone. This review charts multiple biomimetic strategies to help heal bony defects in large and small osseous injury sites, with a special focus on cell transplantation.

Effect of molding pressure on fabrication of low-crystalline calcite block.

PubMed

Lin, Xin; Matsuya, Shigeki; Nakagawa, Masaharu; Terada, Yoshihiro; Ishikawa, Kunio

2008-02-01

We have reported that low-crystalline porous calcite block, which is useful as a bone substitute or a source material to prepare apatite-type bone fillers could be fabricated by exposing calcium hydroxide compact to carbon dioxide gas saturated with water vapor. In the present study, we investigated the effect of molding pressure on the transformation of calcium hydroxide into calcite and the mechanical strength of the carbonated compact. Transformation into calcite was almost completed within 72 h, however, a small amount of Ca(OH)(2) still remained unreacted at higher molding pressure because of incomplete penetration of CO(2) gas into the interparticle space due to dense packing of Ca(OH)(2) particles. On the other hand, high molding pressure resulted in an increase in diametral tensile strength (DTS) of the calcite compact formed. Critical porosity of the calcite block was calculated as approximately 68%.

Fabrication and characterization of magnesium scaffold using different processing parameters

NASA Astrophysics Data System (ADS)

Toghyani, Saeid; Khodaei, Mohammad

2018-03-01

Structural and mechanical properties of scaffolds are important for hard tissue reconstruction. In this study, magnesium scaffolds were fabricated using space holder method for bone tissue reconstruction and the effect of cold compaction pressure and also volume percent of porosity on structural and mechanical properties of scaffolds were investigated using scanning electron microscopy (SEM) and uniaxial compression test. The carbamide spacer agent was also removed after pellet compaction, using NaOH solution and ethanol for the first time and their effect on phases present in scaffold after sintering was investigated using x-ray diffraction (XRD) analysis. Based on the results of mechanical and structural assessments, the optimum cold compaction pressure was selected 350 MPa for pellet compaction. The elastic modulus and strength of magnesium scaffolds including 67 vol.% porosity were in the range of 0.20–0.28 GPa and 4–4.25 MPa, respectively which is comparable to cancellous bone tissue. The mechanical properties of magnesium scaffolds decreased by increasing the porosity. The results also revealed that ethanol is a more suitable liquid for carbamide removal compared to NaOH solution.

[Stereological analysis of rat bone tissue after a flight on the Kosmos-1129 biosatellite].

PubMed

Prokhonchukov, A A; Peschanskiĭ, V S

1982-01-01

Stereological measurements of volume fractions of 53 samples of compact and spongy structures of bones of 15 rats were carried out. The measurements were performed on cortical lamellae, trabecules and lacunae, channels of osteons and matrices of femoral, tibial and fibular bones of rats. Postflight no significant changes were seen in the above parameters as compared to the vivarium controls. During readaptation to I g a slight increase in the volume fraction of spongy bones was noted.

Skeletal and body composition evaluation

NASA Technical Reports Server (NTRS)

Mazess, R. B.

1983-01-01

Research on radiation detectors for absorptiometry; analysis of errors affective single photon absorptiometry and development of instrumentation; analysis of errors affecting dual photon absorptiometry and development of instrumentation; comparison of skeletal measurements with other techniques; cooperation with NASA projects for skeletal evaluation in spaceflight (Experiment MO-78) and in laboratory studies with immobilized animals; studies of postmenopausal osteoporosis; organization of scientific meetings and workshops on absorptiometric measurement; and development of instrumentation for measurement of fluid shifts in the human body were performed. Instrumentation was developed that allows accurate and precise (2% error) measurements of mineral content in compact and trabecular bone and of the total skeleton. Instrumentation was also developed to measure fluid shifts in the extremities. Radiation exposure with those procedures is low (2-10 MREM). One hundred seventy three technical reports and one hundred and four published papers of studies from the University of Wisconsin Bone Mineral Lab are listed.

Bone Inner Structure Suggests Increasing Aquatic Adaptations in Desmostylia (Mammalia, Afrotheria)

PubMed Central

Hayashi, Shoji; Houssaye, Alexandra; Nakajima, Yasuhisa; Chiba, Kentaro; Ando, Tatsuro; Sawamura, Hiroshi; Inuzuka, Norihisa; Kaneko, Naotomo; Osaki, Tomohiro

2013-01-01

Background The paleoecology of desmostylians has been discussed controversially with a general consensus that desmostylians were aquatic or semi-aquatic to some extent. Bone microanatomy can be used as a powerful tool to infer habitat preference of extinct animals. However, bone microanatomical studies of desmostylians are extremely scarce. Methodology/Principal Findings We analyzed the histology and microanatomy of several desmostylians using thin-sections and CT scans of ribs, humeri, femora and vertebrae. Comparisons with extant mammals allowed us to better understand the mode of life and evolutionary history of these taxa. Desmostylian ribs and long bones generally lack a medullary cavity. This trait has been interpreted as an aquatic adaptation among amniotes. Behemotops and Paleoparadoxia show osteosclerosis (i.e. increase in bone compactness), and Ashoroa pachyosteosclerosis (i.e. combined increase in bone volume and compactness). Conversely, Desmostylus differs from these desmostylians in displaying an osteoporotic-like pattern. Conclusions/Significance In living taxa, bone mass increase provides hydrostatic buoyancy and body trim control suitable for poorly efficient swimmers, while wholly spongy bones are associated with hydrodynamic buoyancy control in active swimmers. Our study suggests that all desmostylians had achieved an essentially, if not exclusively, aquatic lifestyle. Behemotops, Paleoparadoxia and Ashoroa are interpreted as shallow water swimmers, either hovering slowly at a preferred depth, or walking on the bottom, and Desmostylus as a more active swimmer with a peculiar habitat and feeding strategy within Desmostylia. Therefore, desmostylians are, with cetaceans, the second mammal group showing a shift from bone mass increase to a spongy inner organization of bones in their evolutionary history. PMID:23565143

Radiographic evidence of disuse osteoporosis in the monkey /M. nemestrina/

NASA Technical Reports Server (NTRS)

Young, D. R.; Schneider, V. S.

1981-01-01

Radiological techniques were utilized for monitoring progressive changes in compact bone in the tibia of monkeys during experimentally induced osteopenia. Bone mass loss in the tibia during restraint was evaluated from radiographs, from bone mineral analysis, and from images reconstructed from gamma ray computerized tomography. The losses during 6 months of restraint tended to occur predominantly in the proximal tibia and were characterized by subperiosteal bone loss, intracortical striations, and scalloped endosteal surfaces. Bone mineral content in the cross section of the tibia declined 17-21%. In 6 months of recovery, the mineral content of the proximal tibia remained depressed.

Bioactive glass (type 45S5) nanoparticles: in vitro reactivity on nanoscale and biocompatibility

NASA Astrophysics Data System (ADS)

Mačković, M.; Hoppe, A.; Detsch, R.; Mohn, D.; Stark, W. J.; Spiecker, E.; Boccaccini, A. R.

2012-07-01

Bioactive glasses represent important biomaterials being investigated for the repair and reconstruction of diseased bone tissues, as they exhibit outstanding bonding properties to human bone. In this study, bioactive glass (type 45S5) nanoparticles (nBG) with a mean particle size in the range of 20-60 nm, synthesised by flame spray synthesis, are investigated in relation to in vitro bioreactivity in simulated body fluid (SBF) and response to osteoblast cells. The structure and kinetics of hydroxyapatite formation in SBF were investigated using transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) revealing a very rapid transformation (after 1 day) of nBG to nanocrystalline bone-like carbonated HAp. Additionally, calcite is formed after 1 day of SBF immersion because of the high surface reactivity of the nBG particles. In the initial state, nBG particles were found to exhibit chain-like porous agglomerates of amorphous nature which are transformed on immersion in SBF into compact agglomerates covered by hydroxyapatite with a reduced size of the primary nanoparticles. In vitro studies revealed high cytocompatibility of nBG with human osteoblast cells, indicated through high lactatedehydrogenase (LDH) and mitochondrial activity as well as alkaline phosphatase activity. Hence, this study contributes to the understanding of the structure and bioactivity of bioactive glass (type 45S5) nanoparticles, providing insights to the phenomena occurring at the nanoscale after immersion in SBF. The results are relevant in relation to the understanding of the nanoparticles' bioreactivity required for applications in bone tissue engineering.

Development of a Portable Knee Rehabilitation Device That Uses Mechanical Loading.

PubMed

Fitzwater, Daric; Dodge, Todd; Chien, Stanley; Yokota, Hiroki; Anwar, Sohel

2013-12-01

Joint loading is a recently developed mechanical modality, which potentially provides a therapeutic regimen to activate bone formation and prevent degradation of joint tissues. To our knowledge, however, few joint loading devices are available for clinical or point-of-care applications. Using a voice-coil actuator, we developed an electromechanical loading system appropriate for human studies and preclinical trials that should prove both safe and effective. Two specific tasks for this loading system were development of loading conditions (magnitude and frequency) suitable for humans, and provision of a convenient and portable joint loading apparatus. Desktop devices have been previously designed to evaluate the effects of various loading conditions using small and large animals. However, a portable knee loading device is more desirable from a usability point of view. In this paper, we present such a device that is designed to be portable, providing a compact, user-friendly loader. The portable device was employed to evaluate its capabilities using a human knee model. The portable device was characterized for force-pulse width modulation duty cycle and loading frequency properties. The results demonstrate that the device is capable of producing the necessary magnitude of forces at appropriate frequencies to promote the stimulation of bone growth and which can be used in clinical studies for further evaluations.

Monitoring the osseointegration process in porous Ti6Al4V implants produced by additive manufacturing: an experimental study in sheep.

PubMed

Kayacan, Mehmet C; Baykal, Yakup B; Karaaslan, Tamer; Özsoy, Koray; Alaca, İlker; Duman, Burhan; Delikanlı, Yunus E

2018-04-01

This study investigated the design and osseointegration process of transitive porous implants that can be used in humans and all trabecular and compact bone structure animals. The aim was to find a way of forming a strong and durable tissue bond on the bone-implant interface. Massive and transitive porous implants were produced on a direct metal laser sintering machine, surgically implanted into the skulls of sheep and kept in place for 12 weeks. At the end of the 12-week period, the Massive and porous implants removed from the sheep were investigated by scanning electron microscopy (SEM) to monitor the osseointegration process. In the literature, each study has selected standard sizes for pore diameter in the structures they use. However, none of these involved transitional porous structures. In this study, as opposed to standard pores, there were spherical or elliptical pores at the micro level, development channels and an inner region. Bone cells developed in the inner region. Transitive pores grown gradually in accordance with the natural structure of the bone were modeled in the inner region for cells to develop. Due to this structure, a strong and durable tissue bond could be formed at the bone-implant interface. Osseointegration processes of Massive vs. porous implants were compared. It was observed that cells were concentrated on the surface of Massive implants. Therefore, osseointegration between implant and bone was less than that of porous implants. In transitive porous implants, as opposed to Massive implants, an outer region was formed in the bone-implant interface that allowed tissue development.

Solving cross-disciplinary problems by mathematical modelling

NASA Astrophysics Data System (ADS)

Panfilov, D. A.; Romanchikov, V. V.; Krupin, K. N.

2018-03-01

The article deals with the creation of a human tibia 3D model by means of “Autodesk Revit-2016” PC based on tomogram data. The model was imported into “Lira- SAPR2013 R4” software system. To assess the possibility of education and the nature of bone fracture (and their visualization), the Finite Element Analysis (FEA) method was used. The geometric parameters of the BBK model corresponded to the physical parameters of the individual. The compact plate different thickness is modeled by rigidity properties of the finite elements in accordance with the parameters on the roentgenogram. The BBK model included parameters of the outer compact plate and the spongy substance having a more developed structure of the epiphysic region. In the “Lira-SAPR2013 R4” software system, mathematical modeling of the traumatic effect was carried out and the analysis of the stress-strain state of the finite element model of the tibia was made to assess fracture conditions.

Design of experiment (DOE) study of biodegradable magnesium alloy synthesized by mechanical alloying using fractional factorial design

NASA Astrophysics Data System (ADS)

Salleh, Emee Marina; Ramakrishnan, Sivakumar; Hussain, Zuhailawati

2014-06-01

The biodegradable nature of magnesium (Mg) makes it a most highlighted and attractive to be used as implant materials. However, rapid corrosion rate of Mg alloys especially in electrolytic aqueous environment limits its performance. In this study, Mg alloy was mechanically milled by incorporating manganese (Mn) as alloying element. An attempt was made to study both effect of mechanical alloying and subsequent consolidation processes on the bulk properties of Mg-Mn alloys. 2k-2 factorial design was employed to determine the significant factors in producing Mg alloy which has properties closes to that of human bones. The design considered six factors (i.e. milling time, milling speed, weight percentage of Mn, compaction pressure, sintering temperature and sintering time). Density and hardness were chosen as the responses for assessing the most significant parameters that affected the bulk properties of Mg-Mn alloys. The experimental variables were evaluated using ANOVA and regression model. The main parameter investigated was compaction pressure.

The Effect of Different Bone Marrow Stimulation Techniques on Human Talar Subchondral Bone: A Micro-Computed Tomography Evaluation.

PubMed

Gianakos, Arianna L; Yasui, Youichi; Fraser, Ethan J; Ross, Keir A; Prado, Marcelo P; Fortier, Lisa A; Kennedy, John G

2016-10-01

To evaluate morphological alterations, microarchitectural disturbances, and the extent of bone marrow access to the subchondral bone marrow compartment using micro-computed tomography analysis in different bone marrow stimulation (BMS) techniques. Nine zones in a 3 × 3 grid pattern were assigned to 5 cadaveric talar dome articular surfaces. A 1.00-mm microfracture awl (s.MFX), a 2.00-mm standard microfracture awl (l.MFX), or a 1.25-mm Kirschner wire (K-wire) drill hole was used to penetrate the subchondral bone in each grid zone. Subchondral bone holes and adjacent tissue areas were assessed by micro-computed tomography to analyze adjacent bone area destruction and communicating channels to the bone marrow. Grades 1 to 3 were assigned, where 1 = minimal compression/sclerosis; 2 = moderate compression/sclerosis; 3 = severe compression/sclerosis. Bone volume/total tissue volume, bone surface area/bone volume, trabecular thickness, and trabecular number were calculated in the region of interest. Visual assessment revealed that the s.MFX had significantly more grade 1 holes (P < .001) and that the l.MFX had significantly more poor/grade 3 holes (P = .002). Bone marrow channel assessment showed a statistically significant increase in the number of channels in the s.MFX when compared with both K-wire and l.MFX holes (P < .001). Bone volume fraction for the s.MFX was significantly less than that of the l.MFX (P = .029). BMS techniques using instruments with larger diameters resulted in increased trabecular compaction and sclerosis in areas adjacent to the defect. K-wire and l.MFX techniques resulted in less open communicating bone marrow channels, denoting a reduction in bone marrow access. The results of this study indicate that BMS using larger diameter devices results in greater microarchitecture disturbances. The current study suggests that the choice of a BMS technique should be carefully considered as the results indicate that smaller diameter hole sizes may diminish the amount of microarchitectural disturbances in the subchondral bone. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Computational segmentation of collagen fibers in bone matrix indicates bone quality in ovariectomized rat spine.

PubMed

Daghma, Diaa Eldin S; Malhan, Deeksha; Simon, Paul; Stötzel, Sabine; Kern, Stefanie; Hassan, Fathi; Lips, Katrin Susanne; Heiss, Christian; El Khassawna, Thaqif

2018-05-01

Bone loss varies according to disease and age and these variations affect bone cells and extracellular matrix. Osteoporosis rat models are widely investigated to assess mechanical and structural properties of bone; however, bone matrix proteins and their discrepant regulation of diseased and aged bone are often overlooked. The current study considered the spine matrix properties of ovariectomized rats (OVX) against control rats (Sham) at 16 months of age. Diseased bone showed less compact structure with inhomogeneous distribution of type 1 collagen (Col1) and changes in osteocyte morphology. Intriguingly, demineralization patches were noticed in the vicinity of blood vessels in the OVX spine. The organic matrix structure was investigated using computational segmentation of collagen fibril properties. In contrast to the aged bone, diseased bone showed longer fibrils and smaller orientation angles. The study shows the potential of quantifying transmission electron microscopy images to predict the mechanical properties of bone tissue.

CALCIUM-47 IN THE STUDY OF BONE PHYSIOLOGY AND PATHOLOGY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerin, R.A.

1962-06-01

The use of Ca/sup 45/, Ca/sup 47/, Ga/sup 67/, and Sr/sup 85/ in the study of Ca metabolism of bone in human subjects is discussed. Ca/sup 47/ is considered to be most suitable because of its short half-life ( approximates 5 days) and high specific activity (10 mc/mg for Ca/sup 47/ Cl/sub 2/). Studies were conducted in 28 patients injected intravenously with Ca/sup 47/; uptake in various bones was followed by external scintillometry for periods up to 11 days later. In healthy subjects the distribution of activity was symmetrical, with highest uptake in sternum and manubrium and lower uptake inmore » cranium (particularly the occipital region), clavicle, and iliac crest. Epiphyses of the long bones showed less avidity for Ca/sup 47/, that in tibia being highest. Sternum fixed 2 to 21/2 more Ca/sup 47/ than the upper tibial epiphysis. This indicates that in the normal adult more Ca is taken up by spongy than compact bone. The Ca/sup 47/ content of bone increased rapidly, reaching a plateau by the 5th or 6th day in most bones and by the 10th day in some, such as clavicle. Studies in pathologic cases showed the very high, but transient, uptake by callus in fractures and and uptake in Paget's disease of bone that was 3 times normal. Higher than normal uptake was also noted in bone lesions in lymphogranulomatosis, where osteogenesis compensating for increased bone destruction could be detected. Pathologic states could also be detected by following the disappearance of Ca/sup 47/ from plasma, it being delayed by hypercalcemia associated with multiple cancer metastases in bone or accelerated by hypocalcemia, such as in Paget's disease. The rate of urinary excretion of radioactivity was also of diagnostic value. (H.H.D.)« less

Regenerative Medicine and Restoration of Joint Function

DTIC Science & Technology

2012-10-01

identify the parameters that generate anatomically shaped bone substitutes of optimal composition and structure with an articulating profile. 2) to develop...strengths. An in vivo study in rabbits to evaluate these materials are ongoing. Task 2. Optimization of SFF Rolling Compaction Parameters : The work is...ongoing related to optimizing SFF rolling compaction parameters to control the density of green samples. We have used CPP powders for these studies

Immobilization-associated osteoporosis in primates

NASA Technical Reports Server (NTRS)

Young, D. R.; Niklowitz, W. J.; Brown, R. J.; Jee, W. S. S.

1986-01-01

Osteopenic changes in the tibial compact bone of fifteen adult male monkeys immobilized for up to 7 months are examined histologically. Osteonal formation in the proximal tibia is analyzed. The analysis reveals the loss of haversian bone in the proximal tibia, increased activation with excessive depth of penetration of osteoclastic activity, rapid bone loss, and resorption cavities of irregular size and orientation. Osteonal formation following reambulation is examined; the recovery of cortical is a repair and rejuvenation process characterized by refilling of resorption cavities and remodeling activities.

Forensic genetic analysis of bone remain samples.

PubMed

Siriboonpiputtana, T; Rinthachai, T; Shotivaranon, J; Peonim, V; Rerkamnuaychoke, B

2018-03-01

DNA typing from degraded human remains is still challenging forensic DNA scientists not only in the prospective of DNA purification but also in the interpretation of established DNA profiles and data manipulation, especially in mass fatalities. In this report, we presented DNA typing protocol to investigate many skeletal remains in different degrees of decomposing. In addition, we established the grading system aiming for prior determination of the association between levels of decomposing and overall STR amplification efficacy. A total of 80 bone samples were subjected to DNA isolation using the modified DNA IQ™ System (Promega, USA) for bone extraction following with STR analysis using the AmpFLSTR Identifiler ® (Thermo Fisher Scientific, USA). In low destruction group, complete STR profiles were observed as 84.4% whereas partial profiles and non-amplified were found as 9.4% and 6.2%, respectively. Moreover, in medium destruction group, both complete and partial STR profiles were observed as 31.2% while 37.5% of this group was unable to amplify. Nevertheless, we could not purify DNA and were unable to generate STR profile in any sample from the high destroyed bone samples. Compact bones such as femur and humerus have high successful amplification rate superior than loose/spongy bones. Furthermore, costal cartilage could be a designate specimen for DNA isolation in a case of the body that was discovered approximately to 3 days after death which enabled to isolate high quality and quantity of DNA, reduce time and cost, and do not require special tools such as freezer mill. Copyright © 2018 Elsevier B.V. All rights reserved.

A Method for the Measurement of Acoustic Impedance and Speed of Sound in a Small Region of Bone using a Fused Quartz Rod as a Transmission Line

NASA Astrophysics Data System (ADS)

Hatakeyama, Rokuro; Yoshizawa, Masazumi; Moriya, Tadashi

2000-11-01

Precise correction for γ-ray attenuation in skull bone has been a significant problem in obtaining quantitative single photon emission computed tomography (SPECT) images. The correction for γ-ray attenuation is approximately proportional to the density and thickness of the bone under investigation. If the acoustic impedance and the speed of sound in bone are measurable using ultrasonic techniques, then the density and thickness of the bone sample can be calculated. Whole bone usually consists of three layers, and each layer has a different ultrasonic character. Thus, the speed of sound must be measured in a small section of each layer in order to determine the overall density of whole bone. It is important to measure the attenuation constant in order to determine the appropriate level for the ultrasonic input signal. We have developed a method for measuring the acoustic impedance, speed of sound, and attenuation constant in a small region of a bone sample using a fused quartz rod as a transmission line. In the present study, we obtained the following results: impedance of compact bone; 5.30(±0.40)× 106 kg/(m2s), speed of sound; 3780± 250 m/s, and attenuation constant; 2.70± 0.50 Np/m. These results were used to obtain the densities of compact bone, spongy bone and bone marrow in a bovine bone sample and as well as the density of pig skull bone, which were found to be 1.40± 0.30 g/cm3, 1.19± 0.50 g/cm3, 0.90± 0.30 g/cm3 and 1.26± 0.30 g/cm3, respectively. Using a thin solid transmission line, the proposed method makes it possible to determine the density of a small region of a bone sample. It is expected that the proposed method, which is based on ultrasonic measurement, will be useful for application in brain SPECT.

Sinus septi nasi: Anatomical study.

PubMed

Mladina, Ranko; Antunović, Romano; Cingi, Cemal; Bayar Muluk, Nuray; Skitarelić, Neven

2017-04-01

The aim of this study was to perform a pioneering investigation into the incidence of pneumatization in human skulls. A total of 93 human skulls (≥20 years of age, 69 males, 24 females) were included in the study. The skulls were scanned in a fixed position using cone beam computed tomography (CBCT). The pneumatized space parameters within the nasal septum-width, length, and height-were measured. Two types of finding were identified: (a) Pneumatization, named "sinus septi nasi" (SSN), and (b) "spongy bone" (SB). The results showed SSN in 32 of the 93 skulls (34.4%). The SSN formations were from 0.5 to 4.2 mm wide, 3.5 to 18.8 mm long, and 3.8 to 17.7 mm high. Tumefactions filled with SB were found in 61 of the 93 skulls (65.59%). These were not suitable for precise measurements since the outer borders were not strictly and well defined on CT scans (perhaps because of the preparation process). In conclusion, the perpendicular plate of the ethmoidal bone is not always compact bone; in 34.4% of cases, it shows a degree of pneumatization. In contrast, an enlarged formation filled with SB is present in 65.59% of cases. The possible sources of pneumatization of this little-investigated region are discussed: sphenoid sinus, frontal sinus, and vomeronasal organ. Clin. Anat. 30:312-317, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Beneath the minerals, a layer of round lipid particles was identified to mediate collagen calcification in compact bone formation.

PubMed

Xu, Shaohua; Yu, Jianqing J

2006-12-01

Astronauts lose 1-2% of their bone minerals per month during space flights. A systematic search for a countermeasure relies on a good understanding of the mechanism of bone formation at the molecular level. How collagen fibers, the dominant matrix protein in bones, are mineralized remains mysterious. Atomic force microscopy was carried out, in combination with immunostaining and Western blotting, on bovine tibia to identify unrecognized building blocks involved in bone formation and for an elucidation of the process of collagen calcification in bone formation. Before demineralization, tiles of hydroxyapatite crystals were found stacked along bundles of collagen fibers. These tiles were homogeneous in size and shape with dimensions 0.69 x 0.77 x 0.2 micro m(3). Demineralization dissolved these tiles and revealed small spheres with an apparent diameter around 145 nm. These spheres appeared to be lipid particles since organic solvents dissolved them. The parallel collagen bundles had widths mostly <2 micro m. Composition analysis of compact bones indicated a high content of apolar lipids, including triglycerides and cholesterol esters. Apolar lipids are known to form lipid droplets or lipoproteins, and these spheres are unlikely to be matrix vesicles as reported for collagen calcification in epiphyseal cartilages. Results from this study suggest that the layer of round lipid particles on collagen fibers mediates the mineral deposition onto the fibers. The homogeneous size of these lipid particles and the presence of apolipoprotein in demineralized bone tissue suggest the possibility that these particles might be of lipoprotein origin. More studies are needed to verify the last claim and to exclude the possibility that they are secreted lipid droplets.

Biomechanics and Mechanobiology of Trabecular Bone: A Review

PubMed Central

Oftadeh, Ramin; Perez-Viloria, Miguel; Villa-Camacho, Juan C.; Vaziri, Ashkan; Nazarian, Ara

2015-01-01

Trabecular bone is a highly porous, heterogeneous, and anisotropic material which can be found at the epiphyses of long bones and in the vertebral bodies. Studying the mechanical properties of trabecular bone is important, since trabecular bone is the main load bearing bone in vertebral bodies and also transfers the load from joints to the compact bone of the cortex of long bones. This review article highlights the high dependency of the mechanical properties of trabecular bone on species, age, anatomic site, loading direction, and size of the sample under consideration. In recent years, high resolution micro finite element methods have been extensively used to specifically address the mechanical properties of the trabecular bone and provide unique tools to interpret and model the mechanical testing experiments. The aims of the current work are to first review the mechanobiology of trabecular bone and then present classical and new approaches for modeling and analyzing the trabecular bone microstructure and macrostructure and corresponding mechanical properties such as elastic properties and strength. PMID:25412137

Deep erosions of the palmar aspect of the navicular bone diagnosed by standing magnetic resonance imaging.

PubMed

Sherlock, C; Mair, T; Blunden, T

2008-11-01

Erosion of the palmar (flexor) aspect of the navicular bone is difficult to diagnose with conventional imaging techniques. To review the clinical, magnetic resonance (MR) and pathological features of deep erosions of the palmar aspect of the navicular bone. Cases of deep erosions of the palmar aspect of the navicular bone, diagnosed by standing low field MR imaging, were selected. Clinical details, results of diagnostic procedures, MR features and pathological findings were reviewed. Deep erosions of the palmar aspect of the navicular bone were diagnosed in 16 mature horses, 6 of which were bilaterally lame. Sudden onset of lameness was recorded in 63%. Radiography prior to MR imaging showed equivocal changes in 7 horses. The MR features consisted of focal areas of intermediate or high signal intensity on T1-, T2*- and T2-weighted images and STIR images affecting the dorsal aspect of the deep digital flexor tendon, the fibrocartilage of the palmar aspect, subchondral compact bone and medulla of the navicular bone. On follow-up, 7/16 horses (44%) had been subjected to euthanasia and only one was being worked at its previous level. Erosions of the palmar aspect of the navicular bone were confirmed post mortem in 2 horses. Histologically, the lesions were characterised by localised degeneration of fibrocartilage with underlying focal osteonecrosis and fibroplasia. The adjacent deep digital flexor tendon showed fibril formation and fibrocartilaginous metaplasia. Deep erosions of the palmar aspect of the navicular bone are more easily diagnosed by standing low field MR imaging than by conventional radiography. The lesions involve degeneration of the palmar fibrocartilage with underlying osteonecrosis and fibroplasia affecting the subchondral compact bone and medulla, and carry a poor prognosis for return to performance. Diagnosis of shallow erosive lesions of the palmar fibrocartilage may allow therapeutic intervention earlier in the disease process, thereby preventing progression to deep erosive lesions.

Complete horizontal skin cell resurfacing and delayed vertical cell infiltration into porcine reconstructive tissue matrix compared to bovine collagen matrix and human dermis.

PubMed

Mirastschijski, Ursula; Kerzel, Corinna; Schnabel, Reinhild; Strauss, Sarah; Breuing, Karl-Heinz

2013-10-01

Xenogenous dermal matrices are used for hernia repair and breast reconstruction. Full-thickness skin replacement is needed after burn or degloving injuries with exposure of tendons or bones. The authors used a human skin organ culture model to study whether porcine reconstructive tissue matrix (Strattice) is effective as a dermal tissue replacement. Skin cells or split-thickness skin grafts were seeded onto human deepidermized dermis, Strattice, and Matriderm. Cellular resurfacing and matrix infiltration were monitored by live fluorescence imaging, histology, and electron microscopy. Proliferation, apoptosis, cell differentiation, and adhesion were analyzed by immunohistochemistry. Epithelial resurfacing and vertical proliferation were reduced and delayed with both bioartificial matrices compared with deepidermized dermis; however, no differences in apoptosis, cell differentiation, or basement membrane formation were found. Vertical penetration was greatest on Matriderm, whereas no matrix infiltration was found on Strattice in the first 12 days. Uncompromised horizontal resurfacing was greatest with Strattice but was absent with Matriderm. Strattice showed no stimulatory effect on cellular inflammation. Matrix texture and surface properties governed cellular performance on tissues. Although dense dermal compaction delayed vertical cellular ingrowth for Strattice, it allowed uncompromised horizontal resurfacing. Dense dermal compaction may slow matrix decomposition and result in prolonged biomechanical stability of the graft. Reconstructive surgeons should choose the adequate matrix substitute depending on biomechanical requirements at the recipient site. Strattice may be suitable as a dermal replacement at recipient sites with high mechanical load requirements.

Compact biomedical pulsed signal generator for bone tissue stimulation

DOEpatents

Kronberg, J.W.

1993-06-08

An apparatus for stimulating bone tissue for stimulating bone growth or treating osteoporosis by applying directly to the skin of the patient an alternating current electrical signal comprising wave forms known to simulate the piezoelectric constituents in bone. The apparatus may, by moving a switch, stimulate bone growth or treat osteoporosis, as desired. Based on low-power CMOS technology and enclosed in a moisture-resistant case shaped to fit comfortably, two astable multivibrators produce the desired waveforms. The amplitude, pulse width and pulse frequency, and the subpulse width and subpulse frequency of the waveforms are adjustable. The apparatus, preferably powered by a standard 9-volt battery, includes signal amplitude sensors and warning signals indicate an output is being produced and the battery needs to be replaced.

Compact biomedical pulsed signal generator for bone tissue stimulation

DOEpatents

Kronberg, James W.

1993-01-01

An apparatus for stimulating bone tissue for stimulating bone growth or treating osteoporosis by applying directly to the skin of the patient an alternating current electrical signal comprising wave forms known to simulate the piezoelectric constituents in bone. The apparatus may, by moving a switch, stimulate bone growth or treat osteoporosis, as desired. Based on low-power CMOS technology and enclosed in a moisture-resistant case shaped to fit comfortably, two astable multivibrators produce the desired waveforms. The amplitude, pulse width and pulse frequency, and the subpulse width and subpulse frequency of the waveforms are adjustable. The apparatus, preferably powered by a standard 9-volt battery, includes signal amplitude sensors and warning signals indicate an output is being produced and the battery needs to be replaced.

Fabrication of porous low crystalline calcite block by carbonation of calcium hydroxide compact.

PubMed

Matsuya, Shigeki; Lin, Xin; Udoh, Koh-ichi; Nakagawa, Masaharu; Shimogoryo, Ryoji; Terada, Yoshihiro; Ishikawa, Kunio

2007-07-01

Calcium carbonate (CaCO(3)) has been widely used as a bone substitute material because of its excellent tissue response and good resorbability. In this experimental study, we propose a new method obtaining porous CaCO(3) monolith for an artificial bone substitute. In the method, calcium hydroxide compacts were exposed to carbon dioxide saturated with water vapor at room temperature. Carbonation completed within 3 days and calcite was the only product. The mechanical strength of CaCO(3) monolith increased with carbonation period and molding pressure. Development of mechanical strength proceeded through two steps; the first rapid increase by bonding with calcite layer formed at the surface of calcium hydroxide particles and the latter increase by the full conversion of calcium hydroxide to calcite. The latter process was thought to be controlled by the diffusion of CO(2) through micropores in the surface calcite layer. Porosity of calcite blocks thus prepared had 36.8-48.1% depending on molding pressure between 1 MPa and 5 MPa. We concluded that the present method may be useful for the preparation of bone substitutes or the preparation of source material for bone substitutes since this method succeeded in fabricating a low-crystalline, and thus a highly reactive, porous calcite block.

Preliminary Testing of a Compact, Bone-Attached Robot for Otologic Surgery

PubMed Central

Dillon, Neal P.; Balachandran, Ramya; dit Falisse, Antoine Motte; Wanna, George B.; Labadie, Robert F.; Withrow, Thomas J.; Fitzpatrick, J. Michael; Webster, Robert J.

2014-01-01

Otologic surgery often involves a mastoidectomy procedure, in which part of the temporal bone is milled away in order to visualize critical structures embedded in the bone and safely access the middle and inner ear. We propose to automate this portion of the surgery using a compact, bone-attached milling robot. A high level of accuracy is required to avoid damage to vital anatomy along the surgical path, most notably the facial nerve, making this procedure well-suited for robotic intervention. In this study, several of the design considerations are discussed and a robot design and prototype are presented. The prototype is a 4 degrees-of-freedom robot similar to a four-axis milling machine that mounts to the patient’s skull. A positioning frame, containing fiducial markers and attachment points for the robot, is rigidly attached to the skull of the patient, and a CT scan is acquired. The target bone volume is manually segmented in the CT by the surgeon and automatically converted to a milling path and robot trajectory. The robot is then attached to the positioning frame and is used to drill the desired volume. The accuracy of the entire system (image processing, planning, robot) was evaluated at several critical locations within or near the target bone volume with a mean free space accuracy result of 0.50 mm or less at all points. A milling test in a phantom material was then performed to evaluate the surgical workflow. The resulting milled volume did not violate any critical structures. PMID:25477726

Microstructure and thermal characterization of dense bone and metals for biomedical use

NASA Astrophysics Data System (ADS)

Rodríguez, G. Peña; Calderón, A.; Hernández, R. A. Muñoz; Orea, A. Cruz; Méndez, M.; Sinencio, F. Sánchez

2000-10-01

We present a microstructural study and thermal diffusivity measurements at room temperature in two different sections of bull dense bone, bull bone and commercial hydroxyapatite, the last two in powder form. A comparison was realised between these measured values and those obtained from metallic samples frequently used in implants, as high purity titanium and 316L stainless steel. Our results show that the porosity and its orientation in the bone are two important factors for the heat flux through the bone. On the other hand, we obtained that the hydroxyapatite, in compact powder form, presents a thermal diffusivity value close to those obtained for the samples of bone which gives a good thermal agreement between these materials. Finally, it was obtained at one order of magnitude difference between the thermal diffusivity values of metallic samples and those corresponding values to bone and hydroxyapatite being this difference greater in titanium than in stainless steel.

42 CFR 137.35 - What is the term of a self-governance compact?

Code of Federal Regulations, 2010 CFR

2010-10-01

....35 Section 137.35 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Self-Governance compact... compact, the compact remains in effect for so long as permitted by Federal law or until terminated by...

Design of Natural Hydroxyapatite as bio-composite ceramics (HAP): Experimental and Numerical Study

NASA Astrophysics Data System (ADS)

Belghazi, Z.; Katundi, D.; Ayari, F.; Bayraktar, E.

2011-01-01

Hydroxyapatite (HAP—Ca10(PO4)6 (OH)2), which exhibits excellent biocompatibility in the body, is one of the most widely used bioactive ceramics for biomedical applications. Along with the ability to carry the load, one of the most important properties of materials used for bone replacement is biocompatibility. In fact, HAP is a bioactive material and it can incorporate into bone structures, supporting bone in-growth without breaking down or dissolving, and it interacts with the living tissue due to the presence of free calcium and phosphate compounds. Generally, Al2O3 powder is added to HAP powder in order to obtain high fracture toughness. Al2O3 has good mechanical properties as compared with HAP, and exhibits extremely high stability with human tissues [1-6]. In this paper, the effect of microwave sintering temperature on the relative density, hardness, and phase purity of compacted bovine Hydroxyapatite (BHA) powder was reported. This research is a comprehensive attempt to develop Hydroxyapatite bio composite ceramics reinforced with alumina—Al2O3, pure titanium and pure pulverised boron powder. A Finite Element (FEM) analysis is also used for modelling to simulate the macroscopic behaviour of this material, taking into account the relevant microscopic scales.

Assessment of mechanical properties of human head tissues for trauma modelling.

PubMed

Lozano-Mínguez, Estívaliz; Palomar, Marta; Infante-García, Diego; Rupérez, María José; Giner, Eugenio

2018-05-01

Many discrepancies are found in the literature regarding the damage and constitutive models for head tissues as well as the values of the constants involved in the constitutive equations. Their proper definition is required for consistent numerical model performance when predicting human head behaviour, and hence skull fracture and brain damage. The objective of this research is to perform a critical review of constitutive models and damage indicators describing human head tissue response under impact loading. A 3D finite element human head model has been generated by using computed tomography images, which has been validated through the comparison to experimental data in the literature. The threshold values of the skull and the scalp that lead to fracture have been analysed. We conclude that (1) compact bone properties are critical in skull fracture, (2) the elastic constants of the cerebrospinal fluid affect the intracranial pressure distribution, and (3) the consideration of brain tissue as a nearly incompressible solid with a high (but not complete) water content offers pressure responses consistent with the experimental data. Copyright © 2018 John Wiley & Sons, Ltd.

Bone matrix structure in different seasons of cervid antlerogenesis and gestation

NASA Astrophysics Data System (ADS)

Silvennoinen, Raimo V. J.; Nygren, Kaarlo; Rouvinen, Juha; Petrova, Valentina V.

1994-05-01

During the antlerogenesis and gestation, substantial amounts of mineral compounds are removed from the skeleton and transferred to the growing antler or foetus. We have used holographic nondestructive testing for sorting out biomechanically aberrant radioulnar bones of European moose and radiological methods to study, whether observed aberrations are due to changes of the structure of the long bones (radius). In males, these changes were studied in three phases of antler cycle: antlerless season, antler growing and mature antler. In females, the studies were made with samples of adult individuals in and after gestation period. We studied x-ray diffraction responses of the bones before and after compression up to saturation level. Our results are indicating that compact and spongy part of the bones are giving seasonally different biomechanical responses.

Isolation and Characterisation of Mesenchymal Stem Cells from Rat Bone Marrow and the Endosteal Niche: A Comparative Study

PubMed Central

Yusop, Norhayati; Battersby, Paul; Alraies, Amr; Moseley, Ryan

2018-01-01

Within bone, mesenchymal stromal cells (MSCs) exist within the bone marrow stroma (BM-MSC) and the endosteal niche, as cells lining compact bone (CB-MSCs). This study isolated and characterised heterogeneous MSC populations from each niche and subsequently investigated the effects of extensive cell expansion, analysing population doublings (PDs)/cellular senescence, colony-forming efficiencies (CFEs), MSC cell marker expression, and osteogenic/adipogenic differentiation. CB-MSCs and BM-MSCs demonstrated similar morphologies and PDs, reaching 100 PDs. Both populations exhibited consistent telomere lengths (12–17 kb), minimal senescence, and positive telomerase expression. CB-MSCs (PD15) had significantly lower CFEs than PD50. CB-MSCs and BM-MSCs both expressed MSC (CD73/CD90/CD105); embryonic (Nanog) and osteogenic markers (Runx2, osteocalcin) but no hematopoietic markers (CD45). CB-MSCs (PD15) strongly expressed Oct4 and p16INK4A. At early PDs, CB-MSCs possessed a strong osteogenic potency and low potency for adipogenesis, whilst BM-MSCs possessed greater overall bipotentiality for osteogenesis and adipogenesis. At PD50, CB-MSCs demonstrated reduced potency for both osteogenesis and adipogenesis, compared to BM-MSCs at equivalent PDs. This study demonstrates similarities in proliferative and mesenchymal cell characteristics between CB-MSCs and BM-MSCs, but contrasting multipotentiality. Such findings support further comparisons of human CB-MSCs and BM-MSCs, facilitating selection of optimal MSC populations for regenerative medicine purposes. PMID:29765418

Radiation and mechanical unloading effects on mouse vertebral bone: Ground-based models of the spaceflight environment

NASA Astrophysics Data System (ADS)

Alwood, Joshua Stewart

Astronauts on long-duration space missions experience increased ionizing radiation background levels and occasional acute doses of ionizing radiation from solar particle events, in addition to biological challenges introduced by weightlessness. Previous research indicates that cancer radiotherapy damages bone marrow cell populations and reduces mechanical strength of bone. However, the cumulative doses in radiotherapy are an order of magnitude or greater than dose predictions for long-duration space missions. Further detriments to the skeletal system are the disuse and mechanical unloading experienced during weightlessness, which causes osteopenia in weight-bearing cancellous bone (a sponge-like bony network of rods, plates and voids) and cortical bone (dense, compact bone). Studies of radiation exposure utilizing spaceflight-relevant types and doses, and in combination with mechanical unloading, have received little attention. Motivated by the future human exploration of the solar system, the effects of acute and increased background radiation on astronaut skeletal health are important areas of study in order to prevent osteopenic deterioration and, ultimately, skeletal fracture. This dissertation addresses how spaceflight-relevant radiation affects bone microarchitecture and mechanical properties in the cancellous-rich vertebrae and compares results to that of mechanical unloading. In addition, a period of re-ambulation is used to test whether animals recover skeletal tissue after irradiation. Whether radiation exposure displays synergism with mechanical unloading is further investigated. Finite element structural and statistical analyses are used to investigate how changes in architecture affect mechanical stress within the vertebra and to interpret the mechanical testing results. In this dissertation, ground-based models provide evidence that ionizing radiation, both highly energetic gamma-rays and charged iron ions, resulted in a persistent loss of cancellous bone in male mice. Mechanical unloading, by contrast, is shown to cause bone loss in the vertebrae via cancellous and cortical thinning that resulted in decreased whole-bone mechanical properties. The effects of mechanical unloading were altogether reversible in the vertebra after re-ambulation, though some residual alteration of trabecular morphology persisted. The combination of unloading and radiation exposure appeared to worsen the reductions of strength. Under either environmental condition, cancellous bone loss occurred near the vertebral endplates and at the centrum midplane. Finite element analysis suggested that tissue-level stresses increase in the centrum after either unloading or irradiation in agreement with the cellular-solid model of dense, plate-like trabeculae. Force-sharing between cancellous and cortical bone decreased after radiation, with stress concentrating on the cortex. In conclusion, acute exposure to spaceflight-relevant ionizing radiation altered trabecular microarchitecture and stress distribution, without a loss of whole-bone strength at the endpoints investigated, while unloading presented the greater immediate detriment to whole-bone mechanical properties. From a skeletal-health perspective, strategies to mitigate and counteract astronaut exposure to acute doses of radiation and mechanical unloading should be developed in preparation for long-term human spaceflight.

A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

PubMed Central

Thibaudeau, Laure; Taubenberger, Anna V.; Holzapfel, Boris M.; Quent, Verena M.; Fuehrmann, Tobias; Hesami, Parisa; Brown, Toby D.; Dalton, Paul D.; Power, Carl A.; Hollier, Brett G.; Hutmacher, Dietmar W.

2014-01-01

ABSTRACT The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact ‘organ’ bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo. PMID:24713276

Histological and compositional responses of bone to immobilization and other experimental conditions

NASA Technical Reports Server (NTRS)

Brown, R. J.; Niklowitz, W. J.

1985-01-01

Histological techniques were utilized for evaluating progressive changes in tibial compact bone in adult male monkeys during chronic studies of immobilization-associated osteopenia. The animals were restrained in a semirecumbent position which reduces normally occurring stresses in the lower extremities and results in bone mass loss. The longest immobilization studies were of seven months duration. Losses of haversian bone tended to occur predominatly in the proximal tibia and were characterized by increased activation with excessive depth of penetration of osteoclastic activity. There was no apparent regulation of the size and orientation of resorption cavities. Rapid bone loss seen during 10 weeks of immobilization appeared to be due to unrestrained osteoclastic activity without controls and regulation which are characteristic of adaptive systems. The general pattern of loss persisted throughout 7 months of immobilization. Clear cut evidence of a formation phase in haversian bone was seen only after two months of reambulation.

Melorheostosis with recurrent soft-tissue components: a histologically confirmed case.

PubMed

Hasegawa, Shoichi; Kanda, Shotaro; Imada, Hiroki; Yamaguchi, Takehiko; Akiyama, Toru

2017-03-01

Melorheostosis is a very rare disorder characterized by irregular cortical thickening seen on radiographs. In this paper, we present a case of melorheostosis with microscopically confirmed soft-tissue components. The patient was a 51-year-old man who complained of severe pain in the lateral aspect of his right knee. The excision of an ossified soft-tissue lesion relieved intractable pain that had lasted 20 years. Microscopically, the cortex of the affected fibula was composed of thick compact bone and the soft-tissue component consisted of dense compact bone without endochondral ossification. The presence of soft-tissue osseous nodules around the joints is one of the specific conditions for melorheostosis and should be differentiated from synovial chondromatosis. The ossified soft-tissue lesion in our patient is to our knowledge the first reported case of the histologically confirmed soft-tissue component of melorheostosis, which differs from that of synovial chondromatosis.

Preparation of Laponite Bioceramics for Potential Bone Tissue Engineering Applications

PubMed Central

Li, Kai; Ju, Yaping; Li, Jipeng; Zhang, Yongxing; Li, Jinhua; Liu, Xuanyong; Shi, Xiangyang; Zhao, Qinghua

2014-01-01

We report a facile approach to preparing laponite (LAP) bioceramics via sintering LAP powder compacts for bone tissue engineering applications. The sintering behavior and mechanical properties of LAP compacts under different temperatures, heating rates, and soaking times were investigated. We show that LAP bioceramic with a smooth and porous surface can be formed at 800°C with a heating rate of 5°C/h for 6 h under air. The formed LAP bioceramic was systematically characterized via different methods. Our results reveal that the LAP bioceramic possesses an excellent surface hydrophilicity and serum absorption capacity, and good cytocompatibility and hemocompatibility as demonstrated by resazurin reduction assay of rat mesenchymal stem cells (rMSCs) and hemolytic assay of pig red blood cells, respectively. The potential bone tissue engineering applicability of LAP bioceramic was explored by studying the surface mineralization behavior via soaking in simulated body fluid (SBF), as well as the surface cellular response of rMSCs. Our results suggest that LAP bioceramic is able to induce hydroxyapatite deposition on its surface when soaked in SBF and rMSCs can proliferate well on the LAP bioceramic surface. Most strikingly, alkaline phosphatase activity together with alizarin red staining results reveal that the produced LAP bioceramic is able to induce osteoblast differentiation of rMSCs in growth medium without any inducing factors. Finally, in vivo animal implantation, acute systemic toxicity test and hematoxylin and eosin (H&E)-staining data demonstrate that the prepared LAP bioceramic displays an excellent biosafety and is able to heal the bone defect. Findings from this study suggest that the developed LAP bioceramic holds a great promise for treating bone defects in bone tissue engineering. PMID:24955961

Collection of Human Wastes on Long Missions

NASA Technical Reports Server (NTRS)

Jennings, D. C.; Lewis, T. A.; Brose, H. F.

1986-01-01

Report evaluates and compares three alternative approaches to hygienic containment of human wastes. Three practical means of waste collection: filter-bag collection with compaction by fan suction, canister collection with compaction by force applied to compaction cups or disks, and sleeve collection with compaction by rollers and winding on reel. Potentially useful in airplanes, buses, boats, trains, and campers and temporary toilets for construction sites and outdoor gatherings.

Engineering a humanized bone organ model in mice to study bone metastases.

PubMed

Martine, Laure C; Holzapfel, Boris M; McGovern, Jacqui A; Wagner, Ferdinand; Quent, Verena M; Hesami, Parisa; Wunner, Felix M; Vaquette, Cedryck; De-Juan-Pardo, Elena M; Brown, Toby D; Nowlan, Bianca; Wu, Dan Jing; Hutmacher, Cosmo Orlando; Moi, Davide; Oussenko, Tatiana; Piccinini, Elia; Zandstra, Peter W; Mazzieri, Roberta; Lévesque, Jean-Pierre; Dalton, Paul D; Taubenberger, Anna V; Hutmacher, Dietmar W

2017-04-01

Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM); however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.

Numerical damage models using a structural approach: application in bones and ligaments

NASA Astrophysics Data System (ADS)

Arnoux, P. J.; Bonnoit, J.; Chabrand, P.; Jean, M.; Pithioux, M.

2002-01-01

The purpose of the present study was to apply knowledge of structural properties to perform numerical simulations with models of bones and knee ligaments exposed to dynamic tensile loading leading to tissue damage. Compact bones and knee ligaments exhibit the same geometrical pattern in their different levels of structural hierarchy from the tropocollagen molecule to the fibre. Nevertheless, their mechanical behaviours differ considerably at the fibril level. These differences are due to the contribution of the joints in the microfibril-fibril-fibre assembly and to the mechanical properties of the structural components. Two finite element models of the fibrous bone and ligament structure were used to describe damage in terms of elastoplastic laws or joint decohesion processes.

[Comparative studies on the material performances of natural bone-like apatite from different bone sources].

PubMed

Fan, Xiaoxia; Ren, Haohao; Chen, Shutian; Wang, Guangni; Deng, Tianyu; Chen, Xingtao; Yan, Yonggang

2014-04-01

The compressive strength of the original bone tissue was tested, based on the raw human thigh bone, bovine bone, pig bone and goat bone. The four different bone-like apatites were prepared by calcining the raw bones at 800 degrees C for 8 hours to remove organic components. The comparison of composition and structure of bone-like apatite from different bone sources was carried out with a composition and structure test. The results indicated that the compressive strength of goat bone was similar to that of human thigh bone, reached (135.00 +/- 7.84) MPa; Infrared spectrum (IR), X-ray diffraction (XRD) analysis results showed that the bone-like apatite from goat bone was much closer to the structure and phase composition of bone-like apatite of human bones. Inductively Coupled Plasma (ICP) test results showed that the content of trace elements of bone-like apatite from goat bone was closer to that of apatite of human bone. Energy Dispersive Spectrometer (EDS) results showed that the Ca/P value of bone-like apatite from goat bone was also close to that of human bone, ranged to 1.73 +/- 0.033. Scanning electron microscopy (SEM) patterns indicated that the macrographs of the apatite from human bone and that of goat bone were much similar to each other. Considering all the results above, it could be concluded that the goat bone-like apatite is much similar to that of human bone. It can be used as a potential natural bioceramic material in terms of material properties.

Beads but no collar; the significance of an asymptomatic rib bone healing pattern in infants.

PubMed

Talbert, David

2010-07-01

When a long bone, such as a rib, is broken, the position of the break can be seen in the following weeks by a temporary collar of a collagen based material (callus) which holds the broken ends together during the repair process. However in infants a different pattern is sometimes found at autopsy, in which the repair material occurs as widely spaced "beads" along the shaft of the rib. The consistency of the bead material corresponds to the progress of repair in the normal way, but there is no focal region as would be expected in a clean break or greenstick fracture. It is proposed that this results from micro-fractures in the compact bone forming the outer aspect of the rib when it is bent excessively, during thoracic compression such as required in Cardiopulmonary Resuscitation, (CPR), or when the infant is "grabbed" when about to slip from the hands of a carer. The compact bone surface is covered by a relatively very elastic layer, the periosteum, which carries nerves sensitive to stretch or tearing of this periosteum. It is proposed that the local stretch induced in the periosteum bridging these micro-fractures is insufficient to cause these nerves to signal pain and so the condition is asymptomatic, and may be quite common in infancy. It should not be confused with imposed trauma. Copyright 2010 Elsevier Ltd. All rights reserved.

[Comparation on Haversian system between human and animal bones by imaging analysis].

PubMed

Lu, Hui-Ling; Zheng, Jing; Yao, Ya-Nan; Chen, Sen; Wang, Hui-Pin; Chen, Li-Xian; Guo, Jing-Yuan

2006-04-01

To explore the differences in Haversian system between human and animal bones through imaging analysis and morphology description. Thirty-five slices grinding from human being as well as dog, pig, cow and sheep bones were observed to compare their structure, then were analysed with the researchful microscope. Plexiform bone or oeston band was not found in human bones; There were significant differences in the shape, size, location, density of Haversian system, between human and animal bones. The amount of Haversian lamella and diameter of central canal in human were the biggest; Significant differences in the central canal diameter and total area percentage between human and animal bones were shown by imaging analysis. (1) Plexiform bone and osteon band could be the exclusive index in human bone; (2) There were significant differences in the structure of Haversian system between human and animal bones; (3) The percentage of central canals total area was valuable in species identification through imaging analysis.

Development of hydroxyapatite/polyvinyl alcohol bionanocomposite for prosthesis implants

NASA Astrophysics Data System (ADS)

Karthik, V.; Pabi, S. K.; Chowdhury, S. K. Roy

2018-02-01

Hydroxyapatite (Ca10(PO4)6(OH)2) has similar structural and chemical properties of natural bone mineral and hence widely used as a bone replacement substitute. Natural bone consists of hydroxyapatite and collagen. For mimicking the natural, in the present work, a sintered porous hydroxyapatite component has been vacuum impregnated with Polyvinyl alcohol (PVA), which has better properties like biocompatibility, biodegradability and water- solubility. Hydroxyapatite powders have been made into nanosize to reduce the melting point and hence the sintering temperature. In the present investigation high energy ball mill is used to produce nano-hydroxyapatite powders in bulk quantity by optimizing the milling parameters using stainless steel grinding media. Pellets of 10 mm diameter have been produced from nano- hydroxyapatite powders under different uniaxial compaction pressures. The pellets have been sintered to form porous compacts. The vacuum impregnation of sintered pallets with PVA solution of different strength has been done to find the optimum impregnation condition. Microhardness, compressive strength, wear loss and haemocompatibility of hydroxyapatite ceramics have been studied before and after impregnation of PVA. The nano- hydroxyapatite/PVA composites have superior mechanical properties and reduced wear loss than the non-impregnated porous nano-hydroxyapatite ceramics.

Teneur en uranium et datation U-Th des tissus osseux et dentaires fossiles de la grotte du Lazaret

NASA Astrophysics Data System (ADS)

Michel, Véronique; Falguères, Christophe; Yokoyama, Yuji

1997-09-01

Fossil bone and dental tissues from Lazaret cave and modern ones are here the subject of a comparative microscopical study. Porous tissues such as dentine and bone have retained their Haversian and Tomes canals respectively. However, cracked areas with calcite were detected, indicating a water percolation within porous tissues and an alteration of tissue in places. In addition, compact fossil enamel is particularly well preserved. These results are essential for U-Th and ESR dating application. Uranium contents, U-Th ages of two fossil mandibular tissues, two tibias and of six burnt fossil bones are presented and discussed.

Early changes in the distal intertarsal joint of Dutch Warmblood foals and the influence of exercise on bone density in the third tarsal bone.

PubMed

Barneveld, A; van Weeren, P R

1999-11-01

It was hypothesised that imposition of different exercise levels at a young age would lead to differences in bone density in the third tarsal bone and to difference in the prevalence of pathological lesions that might contribute to the development of bone spavin later in life. Furthermore, based on earlier literature, it was hypothesised that such lesions could be classified as a manifestation of osteochondrosis. Changes in bone density in the third tarsal bone and early pathological changes in the articular cartilage of the distal intertarsal joint were studied in the offspring of sires with radiographic evidence of osteochondrosis in either stifle or hock. Twenty-four foals were studied at age 5 months after having been subjected to different exercise programmes (box-rest, box-rest with sprint training, pasture exercise) from age one week. Nineteen other foals that originally belonged to the same exercise groups were studied at age 11 months, after they had been weaned, housed together and subjected to an identical low level exercise regimen for an additional 6 months. Bone density was quantified using a microscopic technique. Histomorphological analysis was performed semiquantitatively and using high detail radiography techniques. At age 5 months, mean +/- s.d. bone density in the compact bone of the third tarsal bone was significantly lower in the box-rested foals (37 +/- 4%) than in both the trained and pastured foals (48 +/- 7% and 52 +/- 11%, respectively). After 6 months of identical exercise the previously box-rested foals showed an increase in bone density (53 +/- 12%) which became similar to the value found in the formerly pastured foals (52 +/- 8%). Major pathological lesions (chondrocyte necrosis, fragmentation and chondrone formation) of the articular cartilage of the third and central tarsal bones were already present at age 5 months, but were significantly more numerous at 11 months. There was no relation between the number of cartilage lesions and the osteochondrosis status of the foals. Only 2 lesions in 11-month-old foals had histological characteristics compatible with osteochondrosis, all other lesions were degenerative in nature. It is concluded that bone density of the compact bone of the subchondral bone plate in the third tarsal bone reacts strongly to variations in exercise at a very young age. Low bone density, caused by lack of exercise, can be compensated for when exercise is later increased. Pathological changes in the distal intertarsal joint are common at 5 months and increase to 11 months. These lesions are degenerative in nature and seem not to be related to osteochondrosis. Although the clinical relevance of these abnormalities is uncertain, they may be relevant for the development of osteoarthritic processes in this region later in life.

Analysis of compaction initiation in human embryos by using time-lapse cinematography.

PubMed

Iwata, Kyoko; Yumoto, Keitaro; Sugishima, Minako; Mizoguchi, Chizuru; Kai, Yoshiteru; Iba, Yumiko; Mio, Yasuyuki

2014-04-01

To analyze the initiation of compaction in human embryos in vitro by using time-lapse cinematography (TLC), with the goal of determining the precise timing of compaction and clarifying the morphological changes underlying the compaction process. One hundred and fifteen embryos donated by couples with no further need for embryo-transfer were used in this study. Donated embryos were thawed and processed, and then their morphological behavior during the initiation of compaction was dynamically observed via time-lapse cinematography (TLC) for 5 days. Although the initiation of compaction occurred throughout the period from the 4-cell to 16-cell stage, 99 (86.1 %) embryos initiated compaction at the 8-cell stage or later, with initiation at the 8-cell stage being most frequent (22.6 %). Of these 99 embryos, 49.5 % developed into good-quality blastocysts. In contrast, of the 16 (13.9 %) embryos that initiated compaction prior to the 8-cell stage, only 18.8 % developed into good-quality blastocysts. Embryos that initiated compaction before the 8-cell stage showed significantly higher numbers of multinucleated blastomeres, due to asynchronism in nuclear division at the third mitotic division resulting from cytokinetic failure. The initiation of compaction primarily occurs at the third mitotic division or later in human embryos. Embryos that initiate compaction before the 8-cell stage are usually associated with aberrant embryonic development (i.e., cytokinetic failure accompanied by karyokinesis).

Characterization of mechanical properties of hydroxyapatite-silicon-multi walled carbon nano tubes composite coatings synthesized by EPD on NiTi alloys for biomedical application.

PubMed

Khalili, Vida; Khalil-Allafi, Jafar; Sengstock, Christina; Motemani, Yahya; Paulsen, Alexander; Frenzel, Jan; Eggeler, Gunther; Köller, Manfred

2016-06-01

Release of Ni(1+) ions from NiTi alloy into tissue environment, biological response on the surface of NiTi and the allergic reaction of atopic people towards Ni are challengeable issues for biomedical application. In this study, composite coatings of hydroxyapatite-silicon multi walled carbon nano-tubes with 20wt% Silicon and 1wt% multi walled carbon nano-tubes of HA were deposited on a NiTi substrate using electrophoretic methods. The SEM images of coated samples exhibit a continuous and compact morphology for hydroxyapatite-silicon and hydroxyapatite-silicon-multi walled carbon nano-tubes coatings. Nano-indentation analysis on different locations of coatings represents the highest elastic modulus (45.8GPa) for HA-Si-MWCNTs which is between the elastic modulus of NiTi substrate (66.5GPa) and bone tissue (≈30GPa). This results in decrease of stress gradient on coating-substrate-bone interfaces during performance. The results of nano-scratch analysis show the highest critical distance of delamination (2.5mm) and normal load before failure (837mN) as well as highest critical contact pressure for hydroxyapatite-silicon-multi walled carbon nano-tubes coating. The cell culture results show that human mesenchymal stem cells are able to adhere and proliferate on the pure hydroxyapatite and composite coatings. The presence of both silicon and multi walled carbon nano-tubes (CS3) in the hydroxyapatite coating induce more adherence of viable human mesenchymal stem cells in contrast to the HA coated samples with only silicon (CS2). These results make hydroxyapatite-silicon-multi walled carbon nano-tubes a promising composite coating for future bone implant application. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glyoxal Crosslinking of Cell-Seeded Chitosan/Collagen Hydrogels for Bone Regeneration

PubMed Central

Wang, Limin; Stegemann, Jan P.

2011-01-01

Chitosan and collagen are natural biomaterials that have been used extensively in tissue engineering, both separately and as composite materials. Most methods to fabricate chitosan/collagen composites use freeze drying and chemical crosslinking to create stable porous scaffolds, which subsequently can be seeded with cells. In this study, we directly embedded human bone marrow stem cells (hBMSC) in chitosan/collagen materials by initiating gelation using β-glycerophosphate at physiological temperature and pH. We further examined the use of glyoxal, a dialdehyde with relatively low toxicity, to crosslink these materials and characterized the resulting changes in matrix and cell properties. The cytocompatibility of glyoxal and the crosslinked gels were investigated in terms of hBMSC metabolic activity, viability, proliferation, and osteogenic differentiation. These studies revealed that glyoxal was cytocompatible at concentrations below about 1 mM for periods of exposure up to 15 h, though the degree of cell spreading and proliferation were dependent on matrix composition. Glyoxal-crosslinked matrices were stiffer and compacted less than uncrosslinked controls. It was further demonstrated that hBMSC can attach and proliferate in 3D matrices composed of 50/50 chitosan/collagen, and that these materials supported osteogenic differentiation in response to stimulation. Such glyoxal-crosslinked chitosan/collagen composite materials may find utility as cell delivery vehicles for enhancing the repair of bone defects. PMID:21345389

Thermogelling chitosan and collagen composite hydrogels initiated with β-glycerophosphate for bone tissue engineering

PubMed Central

Wang, Limin; Stegemann, Jan P.

2010-01-01

Chitosan and collagen type I are naturally-derived materials used as cell carriers because of their ability to mimic the extracellular environment and direct cell function. In this study beta-glycerophosphate (beta-GP), an osteogenic medium supplement and a weak base, was used to simultaneously initiate gelation of pure chitosan, pure collagen, and chitosan-collagen composite materials at physiological pH and temperature. Adult human bone marrow-derived stem cells (hBMSC) encapsulated in such hydrogels at chitosan/collagen ratios of 100/0, 65/35, 25/75, and 0/100 wt% exhibited high viability at day 1 after encapsulation, but DNA content dropped by about half over 12 days in pure chitosan materials while it increased two-fold in materials containing collagen. Collagen-containing materials compacted more strongly and were significantly stiffer than pure chitosan gels. In monolayer culture, exposure of hBMSC to beta-GP resulted in decreased cell metabolic activity that varied with concentration and exposure time, but washing effectively removed excess beta-GP from hydrogels. The presence of chitosan in materials resulted in higher expression of osterix and bone sialoprotein genes in medium with and without osteogenic supplements. Chitosan also increased alkaline phosphatase activity and calcium deposition in osteogenic medium. Chitosan-collagen composite materials have potential as matrices for cell encapsulation and delivery, or as in situ gel-forming materials for tissue repair. PMID:20170955

Thermogelling chitosan and collagen composite hydrogels initiated with beta-glycerophosphate for bone tissue engineering.

PubMed

Wang, Limin; Stegemann, Jan P

2010-05-01

Chitosan and collagen type I are naturally derived materials used as cell carriers because of their ability to mimic the extracellular environment and direct cell function. In this study beta-glycerophosphate (beta-GP), an osteogenic medium supplement and a weak base, was used to simultaneously initiate gelation of pure chitosan, pure collagen, and chitosan-collagen composite materials at physiological pH and temperature. Adult human bone marrow-derived stem cells (hBMSC) encapsulated in such hydrogels at chitosan/collagen ratios of 100/0, 65/35, 25/75, and 0/100 wt% exhibited high viability at day 1 after encapsulation, but DNA content dropped by about half over 12 days in pure chitosan materials while it increased twofold in materials containing collagen. Collagen-containing materials compacted more strongly and were significantly stiffer than pure chitosan gels. In monolayer culture, exposure of hBMSC to beta-GP resulted in decreased cell metabolic activity that varied with concentration and exposure time, but washing effectively removed excess beta-GP from hydrogels. The presence of chitosan in materials resulted in higher expression of osterix and bone sialoprotein genes in medium with and without osteogenic supplements. Chitosan also increased alkaline phosphatase activity and calcium deposition in osteogenic medium. Chitosan-collagen composite materials have potential as matrices for cell encapsulation and delivery, or as in situ gel-forming materials for tissue repair. Copyright 2010 Elsevier Ltd. All rights reserved.

42 CFR 137.32 - Is a compact required to participate in self-governance?

Code of Federal Regulations, 2010 CFR

2010-10-01

...-governance? 137.32 Section 137.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Self-Governance compact § 137.32 Is a compact required to participate in self-governance? Yes, Tribes must have a...

[The possibilities for the expert diagnostics of the injuries for the purpose of examination of the remains of the strongly burnt and carbonized corpses].

PubMed

Fetisov, V A; Makarov, I Yu; Kovalev, A V; Gusarov, A A; Sarkisyan, B A; Yankovsky, V E

The objective of the present study was the analysis of the publications in the domestic and foreign literature containing the reports concerning the experience with forensic medical expertise of the strongly burnt and carbonized human corpses. Flame is known to sometimes cause injuries simulating the intravital wounds. Such injuries are categorized into the following types. Thermal ruptures reminiscent of the classical stab and slash wounds unaccompanied by swelling and hemorrhage in the surrounding tissues. Thermal epidural hematomas characterized, unlike traumatic hemorrhages, by the loose cellular structure, brown or reddish-brown colour, and localization at the convex surfaces of both hemispheres of the brain. Thermal amputations differs from the intravital injuries in that they have the polished edges as well as the smoothed and rounded ends the bones bearing no residual soft tissues. The morphological picture of the thermal fractures depends on the time and temperature of the thermal impact. As a rule, the compact bone tissue separates into layers in both longitudinal and transverse directions with the formation of even cortical and through cracks of different length and width. The comprehensive investigation of bone injuries accompanied by the alteration of their physical properties makes it possible to determine the type and the sequence of the combined (mechanical and thermal) actions. The bone of the base of the skull and cervical vertebrae sometimes retain the signs of intravital mechanical injuries. Post-mortem tomography provides an important accessory tool for the examination of the remains.

X1: A Robotic Exoskeleton for In-Space Countermeasures and Dynamometry

NASA Technical Reports Server (NTRS)

Rea, Rochelle; Beck, Christopher; Rovekamp, Roger; Diftler, Myron; Neuhaus, Peter

2013-01-01

Bone density loss and muscle atrophy are among the National Aeronautics and Space Administration's (NASA) highest concerns for crew health in space. Countless hours are spent maintaining an exercise regimen aboard the International Space Station (ISS) to counteract the effect of zero-gravity. Looking toward the future, NASA researchers are developing new compact and innovative exercise technologies to maintain crew health as missions increase in length and take humans further out into the solar system. The X1 Exoskeleton, initially designed for assisted mobility on Earth, was quickly theorized to have far-reaching potential as both an in-space countermeasures device and a dynamometry device to measure muscle strength. This lower-extremity device has the ability to assist or resist human movement through the use of actuators positioned at the hips and knees. Multiple points of adjustment allow for a wide range of users, all the while maintaining correct joint alignment. This paper discusses how the X1 Exoskeleton may fit NASA's onorbit countermeasures needs.

Shell bone histology of the long-necked chelid Yaminuechelys (Testudines: Pleurodira) from the late Cretaceous—early Palaeocene of Patagonia with comments on the histogenesis of bone ornamentation

NASA Astrophysics Data System (ADS)

Jannello, Juan Marcos; Cerda, Ignacio A.; de la Fuente, Marcelo S.

2016-04-01

Yaminuechelys is a long-necked chelid turtle whose remains have been recovered from outcrops of the Santonian-Maastrichtian and Danian of South America. With the purpose of providing data about shell sculpturing origin and palaeoecology, the bone histology of several shell elements (including neural, costal, peripheral and plastral plates) of Yaminuechelys is described herein. Histological analysis reveals that Yaminuechelys shares with Chelidae the presence of interwoven structural fibre bundles in the external cortex, and parallel-fibred bone of the internal cortex. The presence of resorption lines in several samples indicates that the particular ornamentation of the external surfaces originated, at least in part, by focalized resorption and new bone deposition. This mechanism for ornamentation origin and maintenance is here described for the first time in a turtle. Compactness of the shell bones is consistent with an aquatic habitat, which supports previous hypothesis based on palaeoenvironmental and morphological data.

Application of continuous-wave terahertz computed tomography for the analysis of chicken bone structure

NASA Astrophysics Data System (ADS)

Li, Bin; Wang, Dayong; Rong, Lu; Zhai, Changchao; Wang, Yunxin; Zhao, Jie

2018-02-01

Terahertz (THz) radiation is able to penetrate many different types of nonpolar and nonmetallic materials without the damaging effects of x-rays. THz technology can be combined with computed tomography (CT) to form THz CT, which is an effective imaging method that is used to visualize the internal structure of a three-dimensional sample as cross-sectional images. Here, we reported an application of THz as the radiation source in CT imaging by replacing the x-rays. In this method, the sample cross section is scanned in all translation and rotation directions. Then, the projection data are reconstructed using a tomographic reconstruction algorithm. Two-dimensional (2-D) cross-sectional images of the chicken ulna were obtained through the continuous-wave (CW) THz CT system. Given by the difference of the THz absorption of different substances, the compact bone and spongy bone inside the chicken ulna are structurally distinguishable in the 2-D cross-sectional images. Using the filtered back projection algorithm, we reconstructed the projection data of the chicken ulna at different projection angle intervals and found that the artifacts and noise in the images are strikingly increased when the projection angle intervals become larger, reflected by the blurred boundary of the compact bone. The quality and fidelity of the 2-D cross-sectional images could be substantially improved by reducing the projection angle intervals. Our experimental data demonstrated a feasible application of the CW THz CT system in biological imaging.

Unexpected skeletal histology of an ichthyosaur from the Middle Jurassic of Patagonia: implications for evolution of bone microstructure among secondary aquatic tetrapods.

PubMed

Talevi, Marianella; Fernández, Marta S

2012-03-01

During the Mesozoic, one of the most significant evolutionary processes was the secondary adaptation of tetrapods to life in water. Several non-related lineages invaded from the terrestrial realms and from the oceans of the entire world. Among these lineages, ichthyosaurs were particularly successful. Advance parvipelvian ichthyosaurs were the first tetrapods to evolve a fish-shaped body profile. The deep skeletal modifications of their bodies, as well as their biology, depict advance ichthyosaurs as the paradigm of secondary adaptation of reptiles to marine life. Functional inferences point to them as off-shore cruising forms, similar to a living tuna, and some of them were capable of deep diving. Bone histology of some genera such as Temnodontosaurus, Stenopterygius, Ichthyosaurus, and Caypullisaurus, characterized by overall cancellous bone, is consistent with the idea of a fish-shaped ichthyosaurs as fast and far cruisers. Here, we provide histological examination of the ribs of the Middle Jurassic parvipelvian Mollesaurus. Contrasting with the bone histology of other parvipelvian, Mollesaurus ribs are characterized by a compact and thick cortex. Our data indicate that the rib cage was heavy and suggest that not all advanced ichthyosaurs were fast cruisers. The compact and dense ribs in these parvipelvian show that advance ichthyosaurs were ecologically more diverse than previously thought and that the lightening of the skeleton reversed, as also occurred in the evolution of cetacean, at least once along the evolutionary history of ichthyosaurs.

Porous Ti-6Al-4V alloy fabricated by spark plasma sintering for biomimetic surface modification.

PubMed

Kon, Masayuki; Hirakata, Luciana M; Asaoka, Kenzo

2004-01-15

Porous compacts with both biological and biomechanical compatibilities and high strength were developed. Spherical powders of Ti-6Al-4V alloy, which were either as received or surface modified with the use of calcium ions by hydrothermal treatment (HTT), were fabricated by a spark plasma sintering process. The porous compacts of pure Ti were used as reference materials. Porosity was approximately 30%, and compressive strengths were 113 and 125 MPa for the as-received Ti alloy powders and those modified by the HTT process, respectively. The bending strength and elastic modulus of as-received Ti alloy powders were 128-178 MPa and 16-18 GPa, respectively. Each of the compacts was immersed in simulated body fluid (SBF). The amount of adsorption/precipitation of calcium phosphate through the compacts was measured by weight change and was observed by SEM. The compacts were covered with calcium phosphate after 2 weeks of immersion in SBF. The compacts of Ti alloy had plenty of precipitated apatite crystals, and modification by HTT accumulated more precipitation. Because calcium phosphate is a mineral component of bone, apatite, which is precipitated on the surface of the compacts, could adsorb proteins and/or drugs such as antibiotics. It is expected that a large amount of proteins and/or drugs could be impregnated when the porous compacts developed are used. Copyright 2003 Wiley Periodicals, Inc.

The Tarsometatarsus of the Ostrich Struthio camelus: Anatomy, Bone Densities, and Structural Mechanics.

PubMed

Gilbert, Meagan M; Snively, Eric; Cotton, John

2016-01-01

The ostrich Struthio camelus reaches the highest speeds of any extant biped, and has been an extraordinary subject for studies of soft-tissue anatomy and dynamics of locomotion. An elongate tarsometatarsus in adult ostriches contributes to their speed. The internal osteology of the tarsometatarsus, and its mechanical response to forces of running, are potentially revealing about ostrich foot function. Computed tomography (CT) reveals anatomy and bone densities in tarsometatarsi of an adult and a young juvenile ostrich. A finite element (FE) model for the adult was constructed with properties of compact and cancellous bone where these respective tissues predominate in the original specimen. The model was subjected to a quasi-static analysis under the midstance ground reaction and muscular forces of a fast run. Anatomy-Metatarsals are divided proximally and distally and unify around a single internal cavity in most adult tarsometatarsus shafts, but the juvenile retains an internal three-part division of metatarsals throughout the element. The juvenile has a sparsely ossified hypotarsus for insertion of the m. fibularis longus, as part of a proximally separate third metatarsal. Bone is denser in all regions of the adult tarsometatarsus, with cancellous bone concentrated at proximal and distal articulations, and highly dense compact bone throughout the shaft. Biomechanics-FE simulations show stress and strain are much greater at midshaft than at force applications, suggesting that shaft bending is the most important stressor of the tarsometatarsus. Contraction of digital flexors, inducing a posterior force at the TMT distal condyles, likely reduces buildup of tensile stresses in the bone by inducing compression at these locations, and counteracts bending loads. Safety factors are high for von Mises stress, consistent with faster running speeds known for ostriches. High safety factors suggest that bone densities and anatomy of the ostrich tarsometatarsus confer strength for selectively critical activities, such as fleeing and kicking predators. Anatomical results and FE modeling of the ostrich tarsometatarsus are a useful baseline for testing the structure's capabilities and constraints for locomotion, through ontogeny and the full step cycle. With this foundation, future analyses can incorporate behaviorally realistic strain rates and distal joint forces, experimental validation, and proximal elements of the ostrich hind limb.

Applications of the direct photon absorption technique for measuring bone mineral content in vivo. Determination of body composition in vivo

NASA Technical Reports Server (NTRS)

Cameron, J. R.

1972-01-01

The bone mineral content, BMC, determined by monoenergetic photon absorption technique, of 29 different locations on the long bones and vertebral columns of 24 skeletons was measured. Compressive tests were made on bone from these locations in which the maximum load and maximum stress were measured. Also the ultimate strain, modulus of elasticity and energy absorbed to failure were determined for compact bone from the femoral diaphysis and cancellous bone from the eighth through eleventh thoracic vertebrae. Correlations and predictive relationships between these parameters were examined to investigate the applicability of using the BMC at sites normally measured in vivo, i.e. radius and ulna in estimating the BMC and/or strength of the spine or femoral neck. It was found that the BMC at sites on the same bone were highly correlated r = 0.95 or better; the BMC at sites on different bones were also highly interrelated, r = 0.85. The BMC at various sites on the long bones could be estimated to between 10 and 15 per cent from the BMC of sites on the radius or ulna.

Fractographic examination of racing greyhound central (navicular) tarsal bone failure surfaces using scanning electron microscopy.

PubMed

Tomlin, J L; Lawes, T J; Blunn, G W; Goodship, A E; Muir, P

2000-09-01

The greyhound is a fatigue fracture model of a short distance running athlete. Greyhounds have a high incidence of central (navicular) tarsal bone (CTB) fractures, which are not associated with overt trauma. We wished to determine whether these fractures occur because of accumulation of fatigue microdamage. We hypothesized that bone from racing dogs would show site-specific microdamage accumulation, causing predisposition to structural failure. We performed a fractographic examination of failure surfaces from fractured bones using scanning electron microscopy and assessed microcracking observed at the failure surface using a visual analog scale. Branching arrays of microcracks were seen in failure surfaces of CTB and adjacent tarsal bones, suggestive of compressive fatigue failure. Branching arrays of microcracks were particularly prevalent in remodeled trabecular bone that had become compact. CTB fractures showed increased microdamage when compared with other in vivo fractures (adjacent tarsal bone and long bone fractures), and ex vivo tarsal fractures induced by monotonic loading (P < 0.02). It was concluded that greyhound racing and training often results in CTB structural failure, because of accumulation and coalescence of branching arrays of fatigue microcracks, the formation of which appears to be predisposed to adapted bone.

Differentiating human bone from animal bone: a review of histological methods.

PubMed

Hillier, Maria L; Bell, Lynne S

2007-03-01

This review brings together a complex and extensive literature to address the question of whether it is possible to distinguish human from nonhuman bone using the histological appearance of cortical bone. The mammalian species included are rat, hare, badger, racoon dog, cat, dog, pig, cow, goat, sheep, deer, horse, water buffalo, bear, nonhuman primates, and human and are therefore not exhaustive, but cover those mammals that may contribute to a North American or Eurasian forensic assemblage. The review has demonstrated that differentiation of human from certain nonhuman species is possible, including small mammals exhibiting Haversian bone tissue and large mammals exhibiting plexiform bone tissue. Pig, cow, goat, sheep, horse, and water buffalo exhibit both plexiform and Haversian bone tissue and where only Haversian bone tissue exists in bone fragments, differentiation of these species from humans is not possible. Other primate Haversian bone tissue is also not distinguishable from humans. Where differentiation using Haversian bone tissue is undertaken, both the general microstructural appearance and measurements of histological structures should be applied. Haversian system diameter and Haversian canal diameter are the most optimal and diagnostic measurements to use. Haversian system density may be usefully applied to provide an upper and lower limit for humans.

42 CFR 137.30 - What is a self-governance compact?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false What is a self-governance compact? 137.30 Section... SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Self-Governance compact § 137.30 What is a self-governance compact? A self-governance compact is a legally binding and mutually...

Decision tree analysis as a supplementary tool to enhance histomorphological differentiation when distinguishing human from non-human cranial bone in both burnt and unburnt states: A feasibility study.

PubMed

Simmons, T; Goodburn, B; Singhrao, S K

2016-01-01

This feasibility study was undertaken to describe and record the histological characteristics of burnt and unburnt cranial bone fragments from human and non-human bones. Reference series of fully mineralized, transverse sections of cranial bone, from all variables and specimen states, were prepared by manual cutting and semi-automated grinding and polishing methods. A photomicrograph catalogue reflecting differences in burnt and unburnt bone from human and non-humans was recorded and qualitative analysis was performed using an established classification system based on primary bone characteristics. The histomorphology associated with human and non-human samples was, for the main part, preserved following burning at high temperature. Clearly, fibro-lamellar complex tissue subtypes, such as plexiform or laminar primary bone, were only present in non-human bones. A decision tree analysis based on histological features provided a definitive identification key for distinguishing human from non-human bone, with an accuracy of 100%. The decision tree for samples where burning was unknown was 96% accurate, and multi-step classification to taxon was possible with 100% accuracy. The results of this feasibility study strongly suggest that histology remains a viable alternative technique if fragments of cranial bone require forensic examination in both burnt and unburnt states. The decision tree analysis may provide an additional but vital tool to enhance data interpretation. Further studies are needed to assess variation in histomorphology taking into account other cranial bones, ontogeny, species and burning conditions. © The Author(s) 2015.

Histological determination of the human origin from dry bone: a cautionary note for subadults.

PubMed

Caccia, Giulia; Magli, Francesca; Tagi, Veronica Maria; Porta, Davide Guido Ampelio; Cummaudo, Marco; Márquez-Grant, Nicholas; Cattaneo, Cristina

2016-01-01

Anthropologists are frequently required to confirm or exclude the human origin of skeletal remains; DNA and protein radioimmunoassays are useful in confirming the human origin of bone fragments but are not always successful. Histology may be the solution, but the young subadult structure could create misinterpretation. Histological tests were conducted on femur and skull of 31 human subjects. Each sample was observed focusing on presence or absence of fibrous bone, lamellar bone, radial lamellar bone, plexiform bone, reticular pattern, osteon banding, Haversian bone, primary osteons, secondary osteon and osteon fragments. Samples were divided into five age classes; 1 (<1 year), 2 (1-5 years), 3 (6-10 years), 4 (11-15 years) and 5 (16-20 years). Regarding femurs, class 1 presented the following: 87.5% fibrous bone, 37.5% plexiform bone, 12.5% reticular pattern and 12.5% lamellar bone radially oriented. Class 2 showed 37.5% of fibrous bone, 12.5% of reticular pattern and 37.5% of osteon banding. In the higher age classes, the classical human structures, lamellar bone and osteons were frequently visible, except for one case of reticular pattern, generally considered a distinctive non-human structure. The situation appeared different for the skull, where there was a lack of similar information, both in human and non-human. An analysis of the percentage of lamellar bone and osteons was conducted on femur and skull fragments. A trend of increase of primary osteon number and a decrease of the lamellar bone area has been detected in the femur. The present study has therefore shed some light on further pitfalls in species determination of subadult bone.

Titanium compacts produced by the pulvimetallurgical hydride-dehydride method for biomedical applications.

PubMed

Barreiro, M M; Grana, D R; Kokubu, G A; Luppo, M I; Mintzer, S; Vigna, G

2010-04-01

Titanium powder production by the hydride-dehydride method has been developed as a non-expensive process. In this work, commercially pure grade two Ti specimens were hydrogenated. The hydrided material was milled in a planetary mill. The hydrided titanium powder was dehydrided and then sieved to obtain a particle size between 37 and 125 microm in order to compare it with a commercial powder produced by chemical reduction with a particle size lower than 150 microm. Cylindrical green compacts were obtained by uniaxial pressing of the powders at 343 MPa and sintering in vacuum. The powders and the density of sintered compacts were characterized, the oxygen content was measured and in vivo tests were performed in the tibia bones of Wistar rats in order to evaluate their biocompatibility. No differences were observed between the materials which were produced either with powders obtained by the hydride-dehydride method or with commercial powders produced by chemical reduction regarding modifications in compactation, sintering and biological behaviour.

Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

PubMed

Croker, Sarah L; Reed, Warren; Donlon, Denise

2016-03-01

The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone thickness data for a range of bones, this study may be able to assist in the identification of some bone fragments by providing another piece of evidence that, used in conjunction with other clues, can provide a likely determination of the origin of a bone fragment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The synthesis, characterisation and in vivo study of a bioceramic for potential tissue regeneration applications

PubMed Central

Poinern, Gérrard Eddy Jai; Brundavanam, Ravi Krishna; Thi Le, Xuan; Nicholls, Philip K.; Cake, Martin A.; Fawcett, Derek

2014-01-01

Hydroxyapatite (HAP) is a biocompatible ceramic that is currently used in a number of current biomedical applications. Recently, nanometre scale forms of HAP have attracted considerable interest due to their close similarity to the inorganic mineral component of the bone matrix found in humans. In this study ultrafine nanometre scale HAP powders were prepared via a wet precipitation method under the influence of ultrasonic irradiation. The resulting powders were compacted and sintered to form a series of ceramic pellets with a sponge-like structure with varying density and porosity. The crystalline structure, size and morphology of the powders and the porous ceramic pellets were investigated using advanced characterization techniques. The pellets demonstrated good biocompatibility, including mixed cell colonisation and matrix deposition, in vivo following surgical implantation into sheep M. latissimus dorsi. PMID:25168046

A Novel Porous Diamond - Titanium Biomaterial: Structure, Microstructure, Physico-Mechanical Properties and Biocompatibility.

PubMed

Guimarães, Zulmira A S; Damatta, Renato A; Guimarães, Renan S; Filgueira, Marcello

2017-01-01

With the aim of introducing permanent prostheses with main properties equivalent to cortical human bone, Ti-diamond composites were processed through powder metallurgy. Grade 1 titanium and mixtures of Ti powder with 2%, 5% and 10 wt% diamond were compacted at 100MPa, and then sintered at 1250°C/2hr/10-6mbar. Sintered samples were studied in the point of view of their microstructures, structures, yield strength and elastic modulus. The results showed that the best addition of diamonds was 2 wt%, which led to a uniform porosity, yield strength of 370MPa and elastic modulus of 13.9 GPa. Samples of Ti and Ti-2% diamond were subjected to in vitro cytotoxicity test, using cultures of VERO cells, and it resulted in a biocompatible and nontoxic composite material.

Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in hair sheep of northeastern Brazil.

PubMed

Dantas, F P M; Medeiros, G X; Figueiredo, A P M; Thompson, K; Riet-Correa, F

2014-01-01

This paper reports a newly described form of skeletal dysplasia affecting Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a short head and in some cases the animals are smaller and more compact than sheep of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face characteristic of the breed. Dwarf lambs were much smaller than normal, with short legs, a domed head with retruded muzzle and protruded mandible, sternal deformities and exophthalmic eyes situated more laterally in the face than normal. Microscopical examination of long bones of the limbs, bones of the base of the skull and vertebrae showed no lesions. Bones from four affected lambs and one control lamb were macerated for morphometric examination. Although the length of the spinal cord was similar, there was disproportionate shortening of the appendicular bones, particularly the distal segments. Thus the disease was defined as a skeletal dysplasia characterized by craniofacial deformity and disproportionate dwarfism. It is suggested that the disease is inherited as an incomplete dominant trait. The shortened face, which is a feature of the Cabugi breed, may represent the heterozygous state and the more severe, often lethal, dwarfism may occur in homozygotes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Localized accumulation of lead within and among bones from lead-dosed goats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cretacci, Yan; Department of Environmental Health Sciences, School of Public Health, The University at Albany, P.O. Box 509, Albany, NY 12201-0509; Parsons, Patrick J., E-mail: pparsons@wadsworth.org

2010-01-15

The principal aim of this study was to gain a better understanding of where lead (Pb) accumulates and how it is distributed, within the bones of dosed goats. Adult goats were periodically dosed with Pb over a number of years for the primary purpose of producing blood pools containing endogenously bound Pb, for the New York State Blood Lead Proficiency Testing Program. Bone samples (e.g., primarily tibia, femur, humerus, and radius) were collected post-mortem from 11 animals and were analyzed for Pb content by acid digestion and electrothermal atomic absorption spectrometry (ETAAS or GFAAS). Average tibia Pb levels were foundmore » to correlate strongly with the cumulative Pb dose (r{sup 2}=0.81). However, the concentration of Pb in different bones and even within a small area of the same bone varied tremendously. Blood-rich trabecular (spongy) bone, such as the patella and calcaneus, were much more enriched in Pb than was cortical (compact) bone. In some dosed animals, the Pb concentration in the tibia was markedly higher at the proximal and distal ends of the bone compared to the mid-shaft. The implications of these findings with regard to the noninvasive measurement of lead in bone by XRF methods are discussed.« less

Identification of proteinaceous material in the bone of the dinosaur Iguanodon.

PubMed

Embery, Graham; Milner, Angela C; Waddington, Rachel J; Hall, Rachel C; Langley, Martin S; Milan, Anna M

2003-01-01

This study has directed attention at the search for bone-related proteins in an extract of demineralized rib bone of the 120 mya Iguanodon. The inner compact bone was demineralized and the GuCl extract resolved into 11 fractions using anion exchange chromatography, which all contained silver-reactive proteins with various amino acid profiles. Two specific fractions, iv and xi, revealed characteristics typical of contemporary phosphoproteins and proteoglycans, respectively. Fraction iv, 43-57 kDa, contained a high ratio of aspartate and serine, although no phosphate was discernable. Fraction xi contained a band of 41-47 kDa and was rich in chondroitin sulphate and hyaluronan. In addition an early eluting fraction was immunoreactive with an antibody against osteocalcin. A cancellous bone fraction from the same bone sample was also analyzed using N-terminal sequencing and revealed potential similarities with cystatin. While we do not claim to have identified the presence of intact proteins, this study has value in demonstrating that extruded extracellular matrix is protected by its capacity to induce mineralization, which subsequently is important in conserving detectable protein products in ancient skeletal tissues.

An in vitro study of adherence of coagulase-negative staphylococci to bone chip columns.

PubMed

Lazarovich, Zilia; Boldur, Ida; Reifer, Rachel; Nitzan, Yeshayahu

2006-09-01

Coagulase-negative staphylococci (CNS) have become a dominant cause of bone infections and their adherence to the infected bones is a prerequisite for the initiation of these infections. In the present study we investigated and compared the adherence of CNS bacteria to human, chicken and rabbit bones. The study was performed using columns made of bone powder from the three different sources, and measurement of the extent of adhesion to bones of CNS bacteria as an in vitro model which is based on particles of matrix that are closely related to the natural matrix. The adhesion to rabbit bone was relatively high, while adhesion to both human and chicken bone columns was lower and almost identical. Pretreatment of the CNS bacteria with sodium periodate, beta-galactosidase or proteinase K significantly inhibited by 50-60% the adhesion to human bones. Pretreatment of CNS bacteria with subinhibitory concentrations of vancomycin or tunicamycin increased their adherence to human bones several-fold. When the bones were pretreated with vancomycin a considerable increase in the adhesion rate of the bacteria to human and chicken bones was seen. A smaller increase in adherence was observed after pretreatment of human bones with the antibiotic tunicamycin. Salicylic acid or benzalkonium chloride (BZC) also resulted in an increase in adhesion to these pretreated bones. From the results obtained it seems that pretreatment of the CNS bacteria with certain reagents exposes adhesins on the surface of the CNS bacteria. On the other hand, pretreatment of the bones with other reagents may enable a better exposure of receptors located on the bone cells and, as a consequence, may improve the adhesion of the CNS bacteria to the treated bones.

On-chip synthesis of fine-tuned bone-seeking hybrid nanoparticles.

PubMed

Hasani-Sadrabadi, Mohammad Mahdi; Dashtimoghadam, Erfan; Bahlakeh, Ghasem; Majedi, Fatemeh S; Keshvari, Hamid; Van Dersarl, Jules J; Bertsch, Arnaud; Panahifar, Arash; Renaud, Philippe; Tayebi, Lobat; Mahmoudi, Morteza; Jacob, Karl I

2015-01-01

Here we report a one-step approach for reproducible synthesis of finely tuned targeting multifunctional hybrid nanoparticles (HNPs). A microfluidic-assisted method was employed for controlled nanoprecipitation of bisphosphonate-conjugated poly(D,L-lactide-co-glycolide) chains, while coencapsulating superparamagnetic iron oxide nanoparticles and the anticancer drug Paclitaxel. Smaller and more compact HNPs with narrower size distribution and higher drug loading were obtained at microfluidic rapid mixing regimen compared with the conventional bulk method. The HNPs were shown to have a strong affinity for hydroxyapatite, as demonstrated in vitro bone-binding assay, which was further supported by molecular dynamics simulation results. In vivo proof of concept study verified the prolonged circulation of targeted microfluidic HNPs. Biodistribution as well as noninvasive bioimaging experiments showed high tumor localization and suppression of targeted HNPs to the bone metastatic tumor. The hybrid bone-targeting nanoparticles with adjustable characteristics can be considered as promising nanoplatforms for various theragnostic applications.

The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans

PubMed Central

2013-01-01

Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized. PMID:23689830

Intracochlear pressure measurements to study bone conduction transmission: State-of-the art and proof of concept of the experimental Procedure

NASA Astrophysics Data System (ADS)

Borgers, Charlotte; van Wieringen, Astrid; D'hondt, Christiane; Verhaert, Nicolas

2018-05-01

The cochlea is the main contributor in bone conduction perception. Measurements of differential pressure in the cochlea give a good estimation of the cochlear input provided by bone conduction stimulation. Recent studies have proven the feasibility of intracochlear pressure measurements in chinchillas and in human temporal bones to study bone conduction. However, similar measurements in fresh-frozen whole human cadaveric heads could give a more realistic representation of the five different transmission pathways of bone conduction to the cochlea compared to human temporal bones. The aim of our study is to develop and validate a framework for intracochlear pressure measurements to evaluate different aspects of bone conduction in whole human cadaveric heads. A proof of concept describing our experimental setup is provided together with the procedure. Additionally, we also present a method to fix the stapes footplate in order to simulate otosclerosis in human temporal bones. The effectiveness of this method is verified by some preliminary results.

The shock response and suitability of Synbone® as a tissue simulant

NASA Astrophysics Data System (ADS)

Appleby-Thomas, G. J.; Fitzmaurice, B. C.; Hameed, A.; Wood, D. C.; Gibson, M. C.; Painter, J.

2017-01-01

The applicability of various materials as human tissue analogues has been a topic of increasing interest in recent years. It allows for more cost-effective experiments to be carried out, but also avoids ethical issues that would arise from using real human tissue. Synbone®, a porous polyurethane material, is commonly used in ballistic experiments as a bone simulant, but until now has not been characterised in terms of its dynamic behaviour. Here, the Hugoniot equation-of-state (EOS) for Synbone® has been derived via a series of plate-impact experiments; highlighting the importance of the underlying material structure in terms of material collapse under high strain-rates. A compaction model was also used for a more extensive analysis of Synbone® and for further comparison of this material to solid polyurethane. This work - following on from previous in-house studies of other tissue analogues - has provided useful data for future simulation of this material. In addition, comparison to dynamic data for other tissue and simulant materials has highlighted the importance of considering tissue as non-monolithic; each layer of tissue should ideally be represented by its own simulant in ballistic experiments. The equation-of-state (EOS) of Synbone® was found to be Us = 0.33up + 0.97; up < 0.55 mm μs-1 and Us=13.87 up2-14.82 up+5.21 ; 0.55 >up<0.95 mm μs-1 , while the compaction Hugoniot curve tended towards the Hugoniot for polyurethane at higher pressures.

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells.

PubMed

Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

2016-11-22

One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells

PubMed Central

Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

2016-01-01

One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes. PMID:27765913

Application of synchrotron radiation computed microtomography for quantification of bone microstructure in human and rat bones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parreiras Nogueira, Liebert; Barroso, Regina Cely; Pereira de Almeida, Andre

2012-05-17

This work aims to evaluate histomorphometric quantification by synchrotron radiation computed microto-mography in bones of human and rat specimens. Bones specimens are classified as normal and pathological (for human samples) and irradiated and non-irradiated samples (for rat ones). Human bones are specimens which were affected by some injury, or not. Rat bones are specimens which were irradiated, simulating radiotherapy procedures, or not. Images were obtained on SYRMEP beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. The system generated 14 {mu}m tomographic images. The quantification of bone structures were performed directly by the 3D rendered images using a home-made software.more » Resolution yielded was excellent what facilitate quantification of bone microstructures.« less

Repatriation and Identification of Finnish World War II Soldiers

PubMed Central

Palo, Jukka U.; Hedman, Minttu; Söderholm, Niklas; Sajantila, Antti

2007-01-01

Aim To present a summary of the organization, field search, repatriation, forensic anthropological examination, and DNA analysis for the purpose of identification of Finnish soldiers with unresolved fate in World War II. Methods Field searches were organized, executed, and financed by the Ministry of Education and the Association for Cherishing the Memory of the Dead of the War. Anthropological examination conducted on human remains retrieved in the field searches was used to establish the minimum number of individuals and description of the skeletal diseases, treatment, anomalies, or injuries. DNA tests were performed by extracting DNA from powdered bones and blood samples from relatives. Mitochondrial DNA (mtDNA) sequence comparisons, together with circumstantial evidence, were used to connect the remains to the putative family members. Results At present, the skeletal remains of about a thousand soldiers have been found and repatriated. In forensic anthropological examination, several injuries related to death were documented. For the total of 181 bone samples, mtDNA HVR-1 and HVR-2 sequences were successfully obtained for 167 (92.3%) and 148 (81.8%) of the samples, respectively. Five samples yielded no reliable sequence data. Our data suggests that mtDNA preserves at least for 60 years in the boreal acidic soil. The quality of the obtained mtDNA sequence data varied depending on the sample bone type, with long compact bones (femur, tibia and humerus) having significantly better (90.0%) success rate than other bones (51.2%). Conclusion Although more than 60 years have passed since the World War II, our experience is that resolving the fate of soldiers missing in action is still of uttermost importance for people having lost their relatives in the war. Although cultural and individual differences may exist, our experience presented here gives a good perspective on the importance of individual identification performed by forensic professionals. PMID:17696308

Atomic scale chemical tomography of human bone

NASA Astrophysics Data System (ADS)

Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

2017-01-01

Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale - the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

78 FR 50104 - Notice of Inventory Completion: U.S. Department of the Interior, National Park Service, San Juan...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... individuals were identified. The 60 associated funerary objects are 1 splinter awl made from deer bone, 1 tip... flakes, 47 non-human skeletal fragments and non-human teeth, and 2 bags of non-human bone. In the Federal... identified. The 34 associated funerary objects are 28 non-human bone fragments, 1 miniature bone club, and 5...

The Tarsometatarsus of the Ostrich Struthio camelus: Anatomy, Bone Densities, and Structural Mechanics

PubMed Central

Gilbert, Meagan M.; Snively, Eric; Cotton, John

2016-01-01

Background The ostrich Struthio camelus reaches the highest speeds of any extant biped, and has been an extraordinary subject for studies of soft-tissue anatomy and dynamics of locomotion. An elongate tarsometatarsus in adult ostriches contributes to their speed. The internal osteology of the tarsometatarsus, and its mechanical response to forces of running, are potentially revealing about ostrich foot function. Methods/Principal Findings Computed tomography (CT) reveals anatomy and bone densities in tarsometatarsi of an adult and a young juvenile ostrich. A finite element (FE) model for the adult was constructed with properties of compact and cancellous bone where these respective tissues predominate in the original specimen. The model was subjected to a quasi-static analysis under the midstance ground reaction and muscular forces of a fast run. Anatomy–Metatarsals are divided proximally and distally and unify around a single internal cavity in most adult tarsometatarsus shafts, but the juvenile retains an internal three-part division of metatarsals throughout the element. The juvenile has a sparsely ossified hypotarsus for insertion of the m. fibularis longus, as part of a proximally separate third metatarsal. Bone is denser in all regions of the adult tarsometatarsus, with cancellous bone concentrated at proximal and distal articulations, and highly dense compact bone throughout the shaft. Biomechanics–FE simulations show stress and strain are much greater at midshaft than at force applications, suggesting that shaft bending is the most important stressor of the tarsometatarsus. Contraction of digital flexors, inducing a posterior force at the TMT distal condyles, likely reduces buildup of tensile stresses in the bone by inducing compression at these locations, and counteracts bending loads. Safety factors are high for von Mises stress, consistent with faster running speeds known for ostriches. Conclusions/Significance High safety factors suggest that bone densities and anatomy of the ostrich tarsometatarsus confer strength for selectively critical activities, such as fleeing and kicking predators. Anatomical results and FE modeling of the ostrich tarsometatarsus are a useful baseline for testing the structure’s capabilities and constraints for locomotion, through ontogeny and the full step cycle. With this foundation, future analyses can incorporate behaviorally realistic strain rates and distal joint forces, experimental validation, and proximal elements of the ostrich hind limb. PMID:27015416

Determination of mechanical stiffness of bone by pQCT measurements: correlation with non-destructive mechanical four-point bending test data.

PubMed

Martin, Daniel E; Severns, Anne E; Kabo, J M J Michael

2004-08-01

Mechanical tests of bone provide valuable information about material and structural properties important for understanding bone pathology in both clinical and research settings, but no previous studies have produced applicable non-invasive, quantitative estimates of bending stiffness. The goal of this study was to evaluate the effectiveness of using peripheral quantitative computed tomography (pQCT) data to accurately compute the bending stiffness of bone. Normal rabbit humeri (N=8) were scanned at their mid-diaphyses using pQCT. The average bone mineral densities and the cross-sectional moments of inertia were computed from the pQCT cross-sections. Bending stiffness was determined as a function of the elastic modulus of compact bone (based on the local bone mineral density), cross-sectional moment of inertia, and simulated quasistatic strain rate. The actual bending stiffness of the bones was determined using four-point bending tests. Comparison of the bending stiffness estimated from the pQCT data and the mechanical bending stiffness revealed excellent correlation (R2=0.96). The bending stiffness from the pQCT data was on average 103% of that obtained from the four-point bending tests. The results indicate that pQCT data can be used to accurately determine the bending stiffness of normal bone. Possible applications include temporal quantification of fracture healing and risk management of osteoporosis or other bone pathologies.

The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

NASA Astrophysics Data System (ADS)

Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

2016-08-01

Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

Disruption of collagen/apatite alignment impairs bone mechanical function in osteoblastic metastasis induced by prostate cancer.

PubMed

Sekita, Aiko; Matsugaki, Aira; Nakano, Takayoshi

2017-04-01

Prostate cancer (PCa) frequently metastasizes to the bone, generally inducing osteoblastic alterations that increase bone brittleness. Although there is growing interest in the management of the physical capability of patients with bone metastasis, the mechanism underlying the impairment of bone mechanical function remains unclear. The alignment of both collagen fibrils and biological apatite (BAp) c-axis, together with bone mineral density, is one of the strongest contributors to bone mechanical function. In this study, we analyzed the bone microstructure of the mouse femurs with and without PCa cell inoculation. Histological assessment revealed that the bone-forming pattern in the PCa-bearing bone was non-directional, resulting in a spongious structure, whereas that in the control bone was unidirectional and layer-by-layer, resulting in a compact lamellar structure. The degree of preferential alignment of collagen fibrils and BAp, which was evaluated by quantitative polarized microscopy and microbeam X-ray diffraction, respectively, were significantly lower in the PCa-bearing bone than in the control bone. Material parameters including Young's modulus and toughness, measured by the three-point bending test, were simultaneously decreased in the PCa-bearing bone. Specifically, there was a significant positive correlation between the degree of BAp c-axis orientation and Young's modulus. In conclusion, the impairment of mechanical function in the PCa-bearing bone is attributable to disruption of the anisotropic microstructure of bone in multiple phases. This is the first report demonstrating that cancer bone metastasis induces disruption of the collagen/BAp alignment in long bones, thereby impairing their mechanical function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Validating in vivo Raman spectroscopy of bone in human subjects

NASA Astrophysics Data System (ADS)

Esmonde-White, Francis W. L.; Morris, Michael D.

2013-03-01

Raman spectroscopy can non-destructively measure properties of bone related to mineral density, mineral composition, and collagen composition. Bone properties can be measured through the skin in animal and human subjects, but correlations between the transcutaneous and exposed bone measurements have only been reported for human cadavers. In this study, we examine human subjects to collect measurements transcutaneously, on surgically exposed bone, and on recovered bone fragments. This data will be used to demonstrate in vivo feasibility and to compare transcutaneous and exposed Raman spectroscopy of bone. A commercially available Raman spectrograph and optical probe operating at 785 nm excitation are used for the in vivo measurements. Requirements for applying Raman spectroscopy during a surgery are also discussed.

Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues

PubMed Central

Coste, Cécile; Neirinckx, Virginie; Sharma, Anil; Agirman, Gulistan; Rogister, Bernard; Foguenne, Jacques; Lallemend, François

2017-01-01

Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow. PMID:28683107

Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

PubMed

Folwarczna, Joanna; Pytlik, Maria; Zych, Maria; Cegieła, Urszula; Kaczmarczyk-Sedlak, Ilona; Nowińska, Barbara; Sliwiński, Leszek

2013-10-01

Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of immediate and delayed loading on peri-implant trabecular structures: a cone beam CT evaluation.

PubMed

Huang, Yan; Van Dessel, Jeroen; Liang, Xin; Depypere, Maarten; Zhong, Weijian; Ma, Guowu; Lambrichts, Ivo; Maes, Frederik; Jacobs, Reinhilde

2014-12-01

To develop a method for characterizing trabecular bone microarchitecture using cone beam computed tomography (CBCT) and to evaluate trabecular bone changes after rehabilitation using immediate versus delayed implant protocols. Six mongrel dogs randomly received 27 titanium implants in the maxillary incisor or mandibular premolar areas, following one of four protocols: (1) normal extraction socket healing; (2) immediate implant placement and immediate loading; (3) delayed implant placement and delayed loading; (4) delayed implant placement and immediate loading. The animals were euthanized at 8 weeks, and block biopsies were scanned using high resolution CBCT. Standard bone structural variables were assessed in coronal, middle, and apical levels. Coronal and middle regions had more compact, more platelike, and thicker trabeculae. Protocols (2), (3), and (4) had significantly higher values (p < 0.001) than protocol (1) for bone surface density, bone surface volume ratio, and connectivity density, while significantly lower values (p < 0.001) were found for trabecular separation and fractal dimension. However, protocols (2), (3), and (4) did not show significantly different bone remodeling. Compared with normal extraction healing, the implant protocols have an improved bone structural integration. Results do not suggest a different bone remodeling pattern when a delayed versus an immediate implant protocol is used. © 2013 Wiley Periodicals, Inc.

A severe combined immunodeficient-hu in vivo mouse model of human primary mantle cell lymphoma.

PubMed

Wang, Michael; Zhang, Liang; Han, Xiaohong; Yang, Jing; Qian, Jianfei; Hong, Sungyoul; Lin, Pei; Shi, Yuankai; Romaguera, Jorge; Kwak, Larry W; Yi, Qing

2008-04-01

To establish a severe combined immunodeficient (SCID)-hu in vivo mouse model of human primary mantle cell lymphoma (MCL) for the study of the biology and novel therapy of human MCL. Primary MCL cells were isolated from spleen, lymph node, bone marrow aspirates, or peripheral blood of six different patients and injected respectively into human bone chips, which had been s.c. implanted in SCID-hu. Circulating human beta(2)-microglobulin in mouse serum was used to monitor the engraftment and growth of patient's MCL cells. H&E staining and immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies were used to confirm the tumor growth and migration. Increasing levels of circulating human beta(2)-microglobulin in mouse serum indicated that the patient's MCL cells were engrafted successfully into human bone chip of SCID-hu mice. The engraftment and growth of patient's MCL cells were dependent on human bone marrow microenvironment. Immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies confirmed that patient's MCL cells were able to not only survive and propagate in the bone marrow microenvironment of the human fetal bone chips, but also similar to the human disease, migrate to lymph nodes, spleen, bone marrow, and gastrointestinal tract of host mice. Treatment of MCL-bearing SCID-hu mice with atiprimod, a novel antitumor compound against the protection of bone marrow stromal cells, induced tumor regression. This is the first human primary MCL animal model that should be useful for the biological and therapeutic research on MCL.

Osteopathia striata with cranial sclerosis: clinical, radiological, and bone histological findings in an adolescent girl.

PubMed

Ward, L M; Rauch, F; Travers, R; Roy, M; Montes, J; Chabot, G; Glorieux, F H

2004-08-15

Osteopathia striata with cranial sclerosis (OS-CS) is a rare skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extra-skeletal anomalies. We provide a comprehensive description of the skeletal phenotype in a French-Canadian girl with a moderate to severe form of sporadic OS-CS. Multiple medical problems, including anal stenosis and the Pierre-Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile, with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical indices of bone and mineral metabolism were within normal limits. Bone densitometry showed increased areal bone mineral density in the skull, trunk, and pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen revealed an increased amount of trabecular bone. Trabeculae were abnormally thick, but there was no evidence of disturbed bone remodeling. In a cranial bone specimen, multiple layers of periosteal bone were found that covered a compact cortical compartment containing tightly packed haversian canals. Bone lamellation was normal in both the iliac and skull samples. Osteoclast differentiation studies showed that peripheral blood osteoclast precursors from this patient formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not explain why bone mass is increased in most skeletal areas of this patient. Cranial histology points to exuberant periosteal bone formation as a potential cause of the cranial sclerosis.

Imaging microfractures and other abnormalities of bone using a supercontinuum laser source with wavelengths in the four NIR optical windows

NASA Astrophysics Data System (ADS)

Sordillo, Laura A.; Sordillo, Peter P.; Budansky, Yury; Leproux, Philippe; Alfano, R. R.

2015-02-01

Many areas of the body such as the tibia have minimal tissue thickness overlying bone. Near-infrared (NIR) optical windows may be used to image more deeply to reveal abnormalities hidden beneath tissue. We report on the potential application of a compact Leukos supercontinuum laser source (model STM-2000-IR) with wavelengths in the four NIR optical windows (from 650 nm to 950 nm, 1,100 nm to 1,350 nm, 1,600 to 1,870, and 2,100 nm to 2,300 nm, respectively) and between 200 - 500 microwatt/nm power, with InGaAs (Goodrich Sensors Inc. SU320- 1.7RT) and InSb detectors (Teledyne Technologies) to image microfractures and abnormalities of bone hidden beneath tissue.

Histomorphological analysis of the variability of the human skeleton: forensic implications.

PubMed

Cummaudo, Marco; Cappella, Annalisa; Biraghi, Miranda; Raffone, Caterina; Màrquez-Grant, Nicholas; Cattaneo, Cristina

2018-01-20

One of the fundamental questions in forensic medicine and anthropology is whether or not a bone or bone fragment is human. Surprisingly at times for the extreme degradation of the bone (charred, old), DNA cannot be successfully performed and one must turn to other methods. Histological analysis at times can be proposed. However, the variability of a single human skeleton has never been tested. Forty-nine thin sections of long, flat, irregular and short bones were obtained from a well-preserved medieval adult human skeleton. A qualitative histomorphological analysis was performed in order to assess the presence of primary and secondary bone and the presence, absence and orientation of vascular canals. No histological sections exhibited woven or fibro-lamellar bone. Long bones showed a higher variability with an alternation within the same section of areas characterized by tightly packed secondary osteons and areas with scattered secondary osteons immersed in a lamellar matrix. Flat and irregular bones appeared to be characterized by a greater uniformity with scattered osteons in abundant interstitial lamellae. Some cases of "osteon banding" and "drifting osteons" were observed. Although Haversian bone represent the most frequent pattern, a histomorphological variability between different bones of the same individual, in different portions of the same bone, and in different parts of the same section has been observed. Therefore, the present study has highlighted the importance of extending research to whole skeletons without focusing only on single bones, in order to have a better understanding of the histological variability of both human and non-human bone.

Dynamics of poroelastic foams

NASA Astrophysics Data System (ADS)

Forterre, Yoel; Sobac, Benjamin

2010-11-01

Soft poroelastic structures are widespread in biological tissues such as cartilaginous joints in bones, blood-filled placentae or plant organs. Here we investigate the dynamics of open elastic foams immersed in viscous fluids, as model soft poroelastic materials. The experiment consists in slowly compacting blocs of polyurethane solid foam embedded in silicon oil-tanks and studying their relaxation to equilibrium when the confining stress is suddenly released. Measurements of the local fluid pressure and foam velocity field are compared with a simple two-phase flow approach. For small initial compactions, the results show quantitative agreement with the classical diffusion theory of soil consolidation (Terzaghi, Biot). On the other hand, for large initial compactions, the dynamics exhibits long relaxation times and decompaction fronts, which are mainly controlled by the highly non-linear mechanical response of the foam. The analogy between this process and the evaporation of a polymer melt close to the glass transition will be briefly discussed.

The safety of bone allografts used in dentistry: a review.

PubMed

Holtzclaw, Dan; Toscano, Nicholas; Eisenlohr, Lisa; Callan, Don

2008-09-01

Recent media reports concerning "stolen body parts" have shaken the public's trust in the safety of and the use of ethical practices involving human allografts. The authors provide a comprehensive review of the safety aspects of human bone allografts. The authors reviewed U.S. government regulations, industry standards, independent industry association guidelines, company guidelines and scientific articles related to the use of human bone allografts in the practice of dentistry published in the English language. The use of human bone allografts in the practice of dentistry involves the steps of procurement, processing, use and tracking. Rigorous donor screening and aseptic proprietary processing programs have rendered the use of human bone allografts safe and effective as a treatment option. When purchasing human bone allografts for the practice of dentistry, one should choose products accredited by the American Association of Tissue Banks for meeting uniformly high safety and quality control measures. Knowledge of human bone allograft procurement, processing, use and tracking procedures may allow dental clinicians to better educate their patients and address concerns about this valuable treatment option.

Human osteocalcin and bone sialoprotein mediating osteomimicry of prostate cancer cells: role of cAMP-dependent protein kinase A signaling pathway.

PubMed

Huang, Wen-Chin; Xie, Zhihui; Konaka, Hiroyuki; Sodek, Jaro; Zhau, Haiyen E; Chung, Leland W K

2005-03-15

Osteocalcin and bone sialoprotein are the most abundant noncollagenous bone matrix proteins expressed by osteoblasts. Surprisingly, osteocalcin and bone sialoprotein are also expressed by malignant but not normal prostate epithelial cells. The purpose of this study is to investigate how osteocalcin and bone sialoprotein expression is regulated in prostate cancer cells. Our investigation revealed that (a) human osteocalcin and bone sialoprotein promoter activities in an androgen-independent prostate cancer cell line of LNCaP lineage, C4-2B, were markedly enhanced 7- to 12-fold in a concentration-dependent manner by conditioned medium collected from prostate cancer and bone stromal cells. (b) Deletion analysis of human osteocalcin and bone sialoprotein promoter regions identified cyclic AMP (cAMP)-responsive elements (CRE) as the critical determinants for conditioned medium-mediated osteocalcin and bone sialoprotein gene expression in prostate cancer cells. Consistent with these results, the protein kinase A (PKA) pathway activators forskolin and dibutyryl cAMP and the PKA pathway inhibitor H-89, respectively, increased or repressed human osteocalcin and bone sialoprotein promoter activities. (c) Electrophoretic mobility shift assay showed that conditioned medium-mediated stimulation of human osteocalcin and bone sialoprotein promoter activities occurs through increased interaction between CRE and CRE-binding protein. (d) Conditioned medium was found to induce human osteocalcin and bone sialoprotein promoter activities via increased CRE/CRE-binding protein interaction in a cell background-dependent manner, with marked stimulation in selected prostate cancer but not bone stromal cells. Collectively, these results suggest that osteocalcin and bone sialoprotein expression is coordinated and regulated through cAMP-dependent PKA signaling, which may define the molecular basis of the osteomimicry exhibited by prostate cancer cells.

Exercise Sensing and Pose Recovery Inference Tool (ESPRIT) - A Compact Stereo-based Motion Capture Solution For Exercise Monitoring

NASA Technical Reports Server (NTRS)

Lee, Mun Wai

2015-01-01

Crew exercise is important during long-duration space flight not only for maintaining health and fitness but also for preventing adverse health problems, such as losses in muscle strength and bone density. Monitoring crew exercise via motion capture and kinematic analysis aids understanding of the effects of microgravity on exercise and helps ensure that exercise prescriptions are effective. Intelligent Automation, Inc., has developed ESPRIT to monitor exercise activities, detect body markers, extract image features, and recover three-dimensional (3D) kinematic body poses. The system relies on prior knowledge and modeling of the human body and on advanced statistical inference techniques to achieve robust and accurate motion capture. In Phase I, the company demonstrated motion capture of several exercises, including walking, curling, and dead lifting. Phase II efforts focused on enhancing algorithms and delivering an ESPRIT prototype for testing and demonstration.

Application of fluoridated hydroxyapatite thin film coatings using KrF pulsed laser deposition.

PubMed

Hashimoto, Yoshiya; Ueda, Mamoru; Kohiga, Yu; Imura, Kazuki; Hontsu, Shigeki

2018-06-08

Fluoridated hydroxyapatite (FHA) was investigated for application as an implant coating for titanium bone substitute materials in dental implants. A KrF pulsed excimer deposition technique was used for film preparation on a titanium plate. The compacts were ablated by laser irradiation at an energy density of 1 J/cm 2 on an area 1×1 mm 2 with the substrate at room temparature. Energydispersive spectrometric analysis of the FHA film revealed peaks of fluorine in addition to calcium and phosphorus. X-ray diffraction revealed the presence of crystalline FHA on the FHA film after a 10 h post annealing treatment at 450°C. The FHA film coating exhibited significant dissolution resistance to sodium phosphate buffer for up to 21 days, and favorable cell attachment of human mesenchymal stem cells compared with HA film. The results of this study suggest that FHA coatings are suitable for real-world implantation applications.

Magnetic field shimming of a permanent magnet using a combination of pieces of permanent magnets and a single-channel shim coil for skeletal age assessment of children

NASA Astrophysics Data System (ADS)

Terada, Y.; Kono, S.; Ishizawa, K.; Inamura, S.; Uchiumi, T.; Tamada, D.; Kose, K.

2013-05-01

We adopted a combination of pieces of permanent magnets and a single-channel (SC) shim coil to shim the magnetic field in a magnetic resonance imaging system dedicated for skeletal age assessment of children. The target magnet was a 0.3-T open and compact permanent magnet tailored to the hand imaging of young children. The homogeneity of the magnetic field was first improved by shimming using pieces of permanent magnets. The residual local inhomogeneity was then compensated for by shimming using the SC shim coil. The effectiveness of the shimming was measured by imaging the left hands of human subjects and evaluating the image quality. The magnetic resonance images for the child subject clearly visualized anatomical structures of all bones necessary for skeletal age assessment, demonstrating the usefulness of combined shimming.

Magnetic field shimming of a permanent magnet using a combination of pieces of permanent magnets and a single-channel shim coil for skeletal age assessment of children.

PubMed

Terada, Y; Kono, S; Ishizawa, K; Inamura, S; Uchiumi, T; Tamada, D; Kose, K

2013-05-01

We adopted a combination of pieces of permanent magnets and a single-channel (SC) shim coil to shim the magnetic field in a magnetic resonance imaging system dedicated for skeletal age assessment of children. The target magnet was a 0.3-T open and compact permanent magnet tailored to the hand imaging of young children. The homogeneity of the magnetic field was first improved by shimming using pieces of permanent magnets. The residual local inhomogeneity was then compensated for by shimming using the SC shim coil. The effectiveness of the shimming was measured by imaging the left hands of human subjects and evaluating the image quality. The magnetic resonance images for the child subject clearly visualized anatomical structures of all bones necessary for skeletal age assessment, demonstrating the usefulness of combined shimming. Copyright © 2013 Elsevier Inc. All rights reserved.

Nanoporous hydroxyapatite/sodium titanate bilayer on titanium implants for improved osteointegration.

PubMed

Carradò, A; Perrin-Schmitt, F; Le, Q V; Giraudel, M; Fischer, C; Koenig, G; Jacomine, L; Behr, L; Chalom, A; Fiette, L; Morlet, A; Pourroy, G

2017-03-01

The aim of this study was to improve the strength and quality of the titanium-hydroxyapatite interface in order to prevent long-term failure of the implanted devices originating from coating delamination and to test it in an in-vivo model. Ti disks and dental commercial implants were etched in Kroll solution. Thermochemical treatments of the acid-etched titanium were combined with sol-gel hydroxyapatite (HA) coating processes to obtain a nanoporous hydroxyapatite/sodium titanate bilayer. The sodium titanate layer was created by incorporating sodium ions onto the Ti surface during a NaOH alkaline treatment and stabilized using a heat treatment. HA layer was added by dip-coating in a sol-gel solution. The bioactivity was assessed in vitro with murine MC3T3-E1 and human SaOs-2 cells. Functional and histopathological evaluations of the coated Ti implants were performed at 22, 34 and 60days of implantation in a dog lower mandible model. Nanoporous hydroxyapatite/sodium titanate bilayer on titanium implants was sensitive neither to crack propagation nor to layer delamination. The in vitro results on murine MC3T3-E1 and human SaOs-2 cells confirm the advantage of this coating regarding the capacity of cell growth and differentiation. Signs of progressive bone incorporation, such as cancellous bone formed in contact with the implant over the existing compact bone, were notable as early as day 22. Overall, osteoconduction and osteointegration mean scores were higher for test implants compared to the controls at 22 and 34 days. Nanoporous hydroxyapatite/sodium titanate bilayer improves the in-vivo osteoconduction and osteointegration. It prevents the delamination during the screwing and it could increase HA-coated dental implant stability without adhesive failures. The combination of thermochemical treatments with dip coating is a low-cost strategy. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation.

PubMed

Koskela, A; Koponen, J; Lehenkari, P; Viluksela, M; Korkalainen, M; Tuukkanen, J

2017-07-28

Perfluoroalkyl substances (PFAS), including two most commonly studied compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely distributed environmental pollutants, used extensively earlier. Due to their toxicological effects the use of PFAS is now regulated. Based on earlier studies on PFOA's distribution in bone and bone marrow in mice, we investigated PFAS levels and their possible link to bone microarchitecture of human femoral bone samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year old female cadaver for PFAS analyses. We also studied how PFOA exposure affects differentiation of human osteoblasts and osteoclasts. PFAS were detectable from all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In cadaver biopsies, lungs and liver contained the highest concentrations of PFAS, whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was present in the bones, PFOA and PFOS were absent. In vitro results showed no disturbance in osteogenic differentiation after PFOA exposure, but in osteoclasts, lower concentrations led to increased resorption, which eventually dropped to zero after increase in PFOA concentration. In conclusion, PFAS are present in bone and have the potential to affect human bone cells partly at environmentally relevant concentrations.

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

PubMed

Ohman, Caroline; Zwierzak, Iwona; Baleani, Massimiliano; Viceconti, Marco

2013-02-01

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.

High-strength mineralized collagen artificial bone

NASA Astrophysics Data System (ADS)

Qiu, Zhi-Ye; Tao, Chun-Sheng; Cui, Helen; Wang, Chang-Ming; Cui, Fu-Zhai

2014-03-01

Mineralized collagen (MC) is a biomimetic material that mimics natural bone matrix in terms of both chemical composition and microstructure. The biomimetic MC possesses good biocompatibility and osteogenic activity, and is capable of guiding bone regeneration as being used for bone defect repair. However, mechanical strength of existing MC artificial bone is too low to provide effective support at human load-bearing sites, so it can only be used for the repair at non-load-bearing sites, such as bone defect filling, bone graft augmentation, and so on. In the present study, a high strength MC artificial bone material was developed by using collagen as the template for the biomimetic mineralization of the calcium phosphate, and then followed by a cold compression molding process with a certain pressure. The appearance and density of the dense MC were similar to those of natural cortical bone, and the phase composition was in conformity with that of animal's cortical bone demonstrated by XRD. Mechanical properties were tested and results showed that the compressive strength was comparable to human cortical bone, while the compressive modulus was as low as human cancellous bone. Such high strength was able to provide effective mechanical support for bone defect repair at human load-bearing sites, and the low compressive modulus can help avoid stress shielding in the application of bone regeneration. Both in vitro cell experiments and in vivo implantation assay demonstrated good biocompatibility of the material, and in vivo stability evaluation indicated that this high-strength MC artificial bone could provide long-term effective mechanical support at human load-bearing sites.

The influence of bone damage on press-fit mechanics.

PubMed

Bishop, Nicholas E; Höhn, Jan-Christian; Rothstock, Stephan; Damm, Niklas B; Morlock, Michael M

2014-04-11

Press-fitting is used to anchor uncemented implants in bone. It relies in part on friction resistance to relative motion at the implant-bone interface to allow bone ingrowth and long-term stability. Frictional shear capacity is related to the interference fit of the implant and the roughness of its surface. It was hypothesised here that a rough implant could generate trabecular bone damage during implantation, which would reduce its stability. A device was constructed to simulate implantation by displacement of angled platens with varying surface finishes (polished, beaded and flaked) onto the surface of an embedded trabecular bone cube, to different nominal interferences. Push-in (implantation) and Pull-out forces were measured and micro-CT scans were made before and after testing to assess permanent bone deformation. Depth of permanent trabecular bone deformation ('damage'), Pull-out force and Radial force all increased with implantation displacement and with implantation force, for all surface roughnesses. The proposed hypothesis was rejected, since primary stability did not decrease with trabecular bone damage. In fact, Pull-out force linearly increased with push-in force, independently of trabecular bone damage or implant surface. This similar behaviour for the different surfaces might be explained by the compaction of bone into the surfaces during push-in so that Pull-out resistance is governed by bone-on-bone, rather than implant surface-on-bone friction. The data suggest that maximum stability is achieved for the maximum implantation force possible (regardless of trabecular bone damage or surface roughness), but this must be limited to prevent periprosthetic cortical bone fracture, patient damage and component malpositioning. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of weight at slaughter and sex on the carcass characteristics of Florida suckling kids.

PubMed

Peña, Francisco; Perea, J; García, A; Acero, R

2007-03-01

The effect of slaughter weight and sex on some carcass traits of suckling kids of the Florida breed was evaluated. A total of 60 kids (30 male and 30 female), fed exclusively on milk replacers, were slaughtered at 7-8kg (group 1), 10-11kg (group 2) or 14-15kg (group 3) of liveweight (mean weights of 7.6kg, 10.8kg and 14.4kg, respectively). Higher slaughter weights decreased the percentage of subproducts (blood, skin, head, feet) and internal organs (lungs+traquea, heart, liver, spleen, thymus) but significantly increased the percentage of intestine and fat depots (omental fat and mesenteric fat). Higher slaughter weights also increased carcass measures (L 40.5 vs 49.1; F 22.5 vs 25.9; G 10.4 vs 14.2; Wr 10.1 vs 13.9; Wth 8.0 vs 10.5; Th 16.5 vs 199; B 32.3 vs 42.4; PT 41.5 vs 50.8), compactness carcass index (96.6 vs 152.3) and compactness leg index (27.5 vs 44.1). Sex only significantly affected the percentages of feet, internal organs, omental fat, measure L, carcass compactness index and hind limb compactness index. The meat colour and fat colour were mainly scored as pale and white respectively in the carcasses of the lightest animals, whereas heavier kids were scored as pink and cream. Slaughter weight also influenced significantly the carcass fatness (score 1 in lightest kids and 2 or 3 in heavier ones). There were no significant (p>0.05) differences between slaughter weight group and sex in dressing percentages. Percentages corresponding to the long leg, back and neck (30-33%, 18-19% and 8-10%, respectively) decreased when the slaughter weight increased, whereas the ribs (23-25%) and the flank (10-11%) increased slightly. The carcasses comprised 57-58% muscle, 22-25% bone, 5-6% subcutaneous fat and 9-12% intermuscular fat. The percentage muscle stayed the same with increasing slaughter weight, whereas the bone decreased and the fat increased. The carcasses of the heavier females contained less lean and more fat than the males. The bone percentage was significantly (p<0.05) lower in the females and the carcass fat percentage was significantly (p<0.05) higher than in the males.

Effects of Recombinant Human Lactoferrin on Osteoblast Growth and Bone Status in Piglets.

PubMed

Li, Qiuling; Zhao, Jie; Hu, Wenping; Wang, Jianwu; Yu, Tian; Dai, Yunping; Li, Ning

2018-04-03

Lactoferrin (LF), an ~80 kDa iron-binding glycoprotein, modulates many biological effects, including antimicrobial and immunomodulatory activities. Recently, it was shown that LF also regulates bone cell activity, suggesting its therapeutic effect on postmenopausal bone loss. However, a minimal amount is known regarding the effects of recombinant human LF (rhLF) supplementation on bone status in young healthy infants. We found osteoblast cell differentiation was significantly promoted in vitro. Furthermore, treatment of human osteoblast cells with rhLF rapidly induced phosphorylation of p44/p42 mitogen-activated protein kinase (p44/p42 MAPK, ERK1/2). In order to investigate the effects of rhLF on bone status in vivo, we used a piglet model, which is a useful model for human infants. Piglets were supplemented with rhLF milk for 30 days. Bone formation markers, Serum calcium concentration, bone mineral density (BMD), bone mineral content (BMC), tibia bone strength, and the overall metabolite profile analysis showed that rhLF was advantageous to the bone growth in piglets. These findings suggest that rhLF supplementation benefits neonate bone health by modulating bone formation.

Interspecies comparison of subchondral bone properties important for cartilage repair.

PubMed

Chevrier, Anik; Kouao, Ahou S M; Picard, Genevieve; Hurtig, Mark B; Buschmann, Michael D

2015-01-01

Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro-CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone of the rabbit trochlea was the most similar to human MFC, where both had a relatively thin bone plate and a more porous and less dense character of subchondral bone. MFC from animals all displayed thicker bone plates, denser and less porous bone and thicker trabeculae, which may be more representative of older or osteoarthritic patients, while both sheep trochlear ridges and the horse lateral trochlea shared some structural features with human MFC. Since several cartilage repair procedures rely on subchondral bone for repair, subchondral properties should be accounted for when choosing animal models to study and test procedures that are intended for human cartilage repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Octacalcium phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans.

PubMed

Kawai, Tadashi; Suzuki, Osamu; Matsui, Keiko; Tanuma, Yuji; Takahashi, Tetsu; Kamakura, Shinji

2017-05-01

Recently it was reported that the implantation of octacalcium phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Inca - interparietal bones in neurocranium of human skulls in central India

PubMed Central

Marathe, RR; Yogesh, AS; Pandit, SV; Joshi, M; Trivedi, GN

2010-01-01

Inca bones are accessory bones found in neurocranium of human skulls. Occurrence of Inca bones is rare as compared to other inter sutural bones such as wormian bones. These Inca ossicles are regarded as variants of the normal. The reporting of such occurrences is inadequate from Central India. Objectives: To find the incidence of Inca variants in Central India. Materials and Methods: In the present study, 380 dried adult human skulls were examined. All specimen samples were procured from various Medical colleges of Central India. They were analyzed for gross incidence, sexual dimorphism and number of fragments of Inca bones. Results: Gross incidence of Inca bones was found to be 1.315 %. Incidence rate was higher in male skulls than female skulls (male: 1.428%; female: 1.176%). The Inca bones frequently occurred signally. Out of the five observed Inca ossicles, two were fragmented. Conclusions: This data gives idea regarding gross incidence, sexual dimorphism and number of fragments of Inca bones in neurocranium of human skulls from Central India. The knowledge of this variable is useful for neurosurgeons, anthropologists and radiologists. PMID:21799611

Inca - interparietal bones in neurocranium of human skulls in central India.

PubMed

Marathe, Rr; Yogesh, As; Pandit, Sv; Joshi, M; Trivedi, Gn

2010-01-01

Inca bones are accessory bones found in neurocranium of human skulls. Occurrence of Inca bones is rare as compared to other inter sutural bones such as wormian bones. These Inca ossicles are regarded as variants of the normal. The reporting of such occurrences is inadequate from Central India. To find the incidence of Inca variants in Central India. In the present study, 380 dried adult human skulls were examined. All specimen samples were procured from various Medical colleges of Central India. They were analyzed for gross incidence, sexual dimorphism and number of fragments of Inca bones. Gross incidence of Inca bones was found to be 1.315 %. Incidence rate was higher in male skulls than female skulls (male: 1.428%; female: 1.176%). The Inca bones frequently occurred signally. Out of the five observed Inca ossicles, two were fragmented. This data gives idea regarding gross incidence, sexual dimorphism and number of fragments of Inca bones in neurocranium of human skulls from Central India. The knowledge of this variable is useful for neurosurgeons, anthropologists and radiologists.

Customized compact neutron activation analysis system to quantify manganese (Mn) in bone in vivo

PubMed Central

Liu, Yingzi; Mostafaei, Farshad; Sowers, Daniel; Hsieh, Mindy; Zheng, Wei; Nie, Linda H

2018-01-01

Objective In the US alone, millions of workers, including over 300 000 welders, are at high risk of occupational manganese (Mn) exposure. Those who have been chronically exposed to excessive amount of Mn can develop severe neurological disorders similar, but not identical, to the idiopathic Parkinson’s disease. One challenge of identifing the health effects of Mn exposure is to find a reliable biomarker for exposure assessment, especially for long-term cumulative exposure. Approach Mn’s long biological half-life as well as its relatively high concentration in bone makes bone Mn (BnMn) a potentially valuable biomarker for Mn exposure. Our group has been working on the development of a deuterium–deuterium (D–D)-based neutron generator to quantify Mn in bone in vivo. Main results and significance In this paper, we report the latest advancements in our system. With a customized hand irradiation assembly, a fully characterized high purity germanium (HPGe) detector system, and an acceptable hand dose of 36 mSv, a detection limit of 0.64 µg Mn/g bone (ppm) has been achieved. PMID:28060775

Relatively well preserved DNA is present in the crystal aggregates of fossil bones

PubMed Central

Salamon, Michal; Tuross, Noreen; Arensburg, Baruch; Weiner, Steve

2005-01-01

DNA from fossil human bones could provide invaluable information about population migrations, genetic relations between different groups and the spread of diseases. The use of ancient DNA from bones to study the genetics of past populations is, however, very often compromised by the altered and degraded state of preservation of the extracted material. The universally observed postmortem degradation, together with the real possibility of contamination with modern human DNA, makes the acquisition of reliable data, from humans in particular, very difficult. We demonstrate that relatively well preserved DNA is occluded within clusters of intergrown bone crystals that are resistant to disaggregation by the strong oxidant NaOCl. We obtained reproducible authentic sequences from both modern and ancient animal bones, including humans, from DNA extracts of crystal aggregates. The treatment with NaOCl also minimizes the possibility of modern DNA contamination. We thus demonstrate the presence of a privileged niche within fossil bone, which contains DNA in a better state of preservation than the DNA present in the total bone. This counterintuitive approach to extracting relatively well preserved DNA from bones significantly improves the chances of obtaining authentic ancient DNA sequences, especially from human bones. PMID:16162675

Is the corticomedullary index valid to distinguish human from nonhuman bones: a multislice computed tomography study.

PubMed

Rérolle, Camille; Saint-Martin, Pauline; Dedouit, Fabrice; Rousseau, Hervé; Telmon, Norbert

2013-09-10

The first step in the identification process of bone remains is to determine whether they are of human or nonhuman origin. This issue may arise when only a fragment of bone is available, as the species of origin is usually easily determined on a complete bone. The present study aims to assess the validity of a morphometric method used by French forensic anthropologists to determine the species of origin: the corticomedullary index (CMI), defined by the ratio of the diameter of the medullary cavity to the total diameter of the bone. We studied the constancy of the CMI from measurements made on computed tomography images (CT scans) of different human bones, and compared our measurements with reference values selected in the literature. The measurements obtained on CT scans at three different sites of 30 human femurs, 24 tibias, and 24 fibulas were compared between themselves and with the CMI reference values for humans, pigs, dogs and sheep. Our results differed significantly from these reference values, with three exceptions: the proximal quarter of the femur and mid-fibular measurements for the human CMI, and the proximal quarter of the tibia for the sheep CMI. Mid-tibial, mid-femoral, and mid-fibular measurements also differed significantly between themselves. Only 22.6% of CT scans of human bones were correctly identified as human. We concluded that the CMI is not an effective method for determining the human origin of bone remains. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Glycation Contributes to Interaction Between Human Bone Alkaline Phosphatase and Collagen Type I.

PubMed

Halling Linder, Cecilia; Enander, Karin; Magnusson, Per

2016-03-01

Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein-protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

Spatial distribution of the trace elements zinc, strontium and lead in human bone tissue☆

PubMed Central

Pemmer, B.; Roschger, A.; Wastl, A.; Hofstaetter, J.G.; Wobrauschek, P.; Simon, R.; Thaler, H.W.; Roschger, P.; Klaushofer, K.; Streli, C.

2013-01-01

Trace elements are chemical elements in minute quantities, which are known to accumulate in the bone. Cortical and trabecular bones consist of bone structural units (BSUs) such as osteons and bone packets of different mineral content and are separated by cement lines. Previous studies investigating trace elements in bone lacked resolution and therefore very little is known about the local concentration of zinc (Zn), strontium (Sr) and lead (Pb) in BSUs of human bone. We used synchrotron radiation induced micro X-ray fluorescence analysis (SR μ-XRF) in combination with quantitative backscattered electron imaging (qBEI) to determine the distribution and accumulation of Zn, Sr, and Pb in human bone tissue. Fourteen human bone samples (10 femoral necks and 4 femoral heads) from individuals with osteoporotic femoral neck fractures as well as from healthy individuals were analyzed. Fluorescence intensity maps were matched with BE images and correlated with calcium (Ca) content. We found that Zn and Pb had significantly increased levels in the cement lines of all samples compared to the surrounding mineralized bone matrix. Pb and Sr levels were found to be correlated with the degree of mineralization. Interestingly, Zn intensities had no correlation with Ca levels. We have shown for the first time that there is a differential accumulation of the trace elements Zn, Pb and Sr in BSUs of human bone indicating different mechanisms of accumulation. PMID:23932972

Ash content of bones in the pigtail monkey, Macaca nemestrina.

NASA Technical Reports Server (NTRS)

Vose, G. P.; Roach, T. L.

1972-01-01

Ash analyses of skeletons of four adult primates, Macaca nemestrina, revealed some similarities and some marked contrasts when compared with published data on human skeletal ash. The skull in both Macaca nemestrina and man has the highest ash content of all bones in the skeleton. While the bones of the arms of humans have an ash content nearly identical to that of the legs (0.3% difference), in Macaca nemestrina the humeri and radii contain 5.4% more ash than the femora and tibiae. Similarly in Macaca nemestrina the bones of the hands contain 3.5% more ash than the bones of the feet, while in humans the same bones agree within 0.3% implying that adaptive use function is a factor in bone ash concentration. The ribs of Macaca nemestrina showed an unexpectedly high ash content in comparison with those of humans. In contrast with the relatively constant ash content throughout the vertebrae in humans, a conspicuous decrease axially was noted in Macaca nemestrina.

An experimental study to investigate biomechanical aspects of the initial stability of press-fit implants.

PubMed

Berahmani, Sanaz; Janssen, Dennis; van Kessel, Sal; Wolfson, David; de Waal Malefijt, Maarten; Buma, Pieter; Verdonschot, Nico

2015-02-01

Initial fixation of press-fit implants depends on interference fit, surface morphology, and bone material properties. To understand the biomechanical effect of each factor and their interactions, the pull-out strength of seven types of CoCrMo tapered implants, with four different interference fits, three different surface morphologies (low, medium and high roughness), and at two time points (0 and 30 min) were tested in trabecular bone with varying density. The effect of interference fit on pull-out strength depended on the surface morphology and time. In contrast with our expectations, samples with a higher roughness had a lower pull-out strength. We found a similar magnitude of bone damage for the different surface morphologies, but the type of damage was different, with bone compaction versus bone abrasion for low and high frictional surfaces, respectively. This explains a reduced sensitivity of fixation strength to bone mineral density in the latter group. In addition, a reduction in fixation strength after a waiting period only occurred for the low frictional specimens. Our study demonstrates that it is essential to evaluate the interplay between different factors and emphasizes the importance of testing in natural bone in order to optimize the initial stability of press-fit implants. Copyright © 2014 Elsevier Ltd. All rights reserved.

THE EFFECT OF BACKGROUND SIGNAL AND ITS REPRESENTATION IN DECONVOLUTION OF EPR SPECTRA ON ACCURACY OF EPR DOSIMETRY IN BONE.

PubMed

Ciesielski, Bartlomiej; Marciniak, Agnieszka; Zientek, Agnieszka; Krefft, Karolina; Cieszyński, Mateusz; Boguś, Piotr; Prawdzik-Dampc, Anita

2016-12-01

This study is about the accuracy of EPR dosimetry in bones based on deconvolution of the experimental spectra into the background (BG) and the radiation-induced signal (RIS) components. The model RIS's were represented by EPR spectra from irradiated enamel or bone powder; the model BG signals by EPR spectra of unirradiated bone samples or by simulated spectra. Samples of compact and trabecular bones were irradiated in the 30-270 Gy range and the intensities of their RIS's were calculated using various combinations of those benchmark spectra. The relationships between the dose and the RIS were linear (R 2  > 0.995), with practically no difference between results obtained when using signals from irradiated enamel or bone as the model RIS. Use of different experimental spectra for the model BG resulted in variations in intercepts of the dose-RIS calibration lines, leading to systematic errors in reconstructed doses, in particular for high- BG samples of trabecular bone. These errors were reduced when simulated spectra instead of the experimental ones were used as the benchmark BG signal in the applied deconvolution procedures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

FROM ANEURYSMAL BONE CYST TO TELANGIECTATIC OSTEOSARCOMA WITH METASTASIS IN INGUINAL LYMPH NODES - CASE REPORT.

PubMed

Janevska, Vesna; Spasevska, Liljana; Samardziski, Milan; Nikodinovskai, Violeta; Zhivadinovik, Julija; Trajkovskai, Elizabeta

2015-01-01

Aneurysmal bone cyst is a benign bone lesion composed of blood filled cystic cavities lined by fibrous septa. Its malignant transformation of is a rare event. We report a case of a lesion in the second metatarsal bone in a 29-year-old male, presented as a slight swelling of the right foot. After the curettage had been done, the diagnosis of aneurysmal bone cyst was made but the recurrence occurred 4 years later. The biopsy of the recurrent tumor showed compact neoplastic tissue consistent with diagnosis of giant cell tumor with malignancy. The malignant component was recognized as a high grade sarcoma with osteoid production. A tumor mass with the whole II metatarsal bone was extirpated and a resected part of fibula was transplanted. A year later, another recurrence occurred, an amputation was performed and a teleangiectatic osteosarcoma with ingvinal lymph nodes metastases was diagnosed. No other tumor mass was confirmed, either clinically or by imaging techniques at the time of his third operation. He died 4 months later with multiple pulmonary metastases. We emphasize the importance of team work in order to achieve the accurate diagnosis, highlighting careful radiological examinations, good sampling and awareness of unusual cases in bone tumor pathology.

Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

DTIC Science & Technology

2014-09-01

13. SUPPLEMENTARY NOTES 14. ABSTRACT Bone is the most common site of metastasis for human breast cancer (BCa), which results in significant...to all major bones as in human patients. 15. SUBJECT TERMS Bone metastasis; osteolysis; osteoprotegerin 16. SECURITY CLASSIFICATION OF: 17...metastasis for human breast cancer (BCa), which results in significant morbidity and mortality in patients with advanced disease. A vicious cycle

Postnatal temporal bone ontogeny in Pan, Gorilla, and Homo, and the implications for temporal bone ontogeny in Australopithecus afarensis.

PubMed

Terhune, Claire E; Kimbel, William H; Lockwood, Charles A

2013-08-01

Assessments of temporal bone morphology have played an important role in taxonomic and phylogenetic evaluations of fossil taxa, and recent three-dimensional analyses of this region have supported the utility of the temporal bone for testing taxonomic and phylogenetic hypotheses. But while clinical analyses have examined aspects of temporal bone ontogeny in humans, the ontogeny of the temporal bone in non-human taxa is less well documented. This study examines ontogenetic allometry of the temporal bone in order to address several research questions related to the pattern and trajectory of temporal bone shape change during ontogeny in the African apes and humans. We further apply these data to a preliminary analysis of temporal bone ontogeny in Australopithecus afarensis. Three-dimensional landmarks were digitized on an ontogenetic series of specimens of Homo sapiens, Pan troglodytes, Pan paniscus, and Gorilla gorilla. Data were analyzed using geometric morphometric methods, and shape changes throughout ontogeny in relation to size were compared. Results of these analyses indicate that, despite broadly similar patterns, African apes and humans show marked differences in development of the mandibular fossa and tympanic portions of the temporal bone. These findings indicate divergent, rather than parallel, postnatal ontogenetic allometric trajectories for temporal bone shape in these taxa. The pattern of temporal bone shape change with size exhibited by A. afarensis showed some affinities to that of humans, but was most similar to extant African apes, particularly Gorilla. Copyright © 2013 Wiley Periodicals, Inc.

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com; O'Shea, Patrick J.; Fagura, Malbinder

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitorsmore » caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and mineralisation produced by GSK-3 inhibition. • In rats, 3 GSK-3 inhibitors produced a unique serum bone turnover biomarker profile. • Enhanced bone formation was seen within 7 to 14 days of compound treatment in rats.« less

Gracility of the modern Homo sapiens skeleton is the result of decreased biomechanical loading.

PubMed

Ryan, Timothy M; Shaw, Colin N

2015-01-13

The postcranial skeleton of modern Homo sapiens is relatively gracile compared with other hominoids and earlier hominins. This gracility predisposes contemporary humans to osteoporosis and increased fracture risk. Explanations for this gracility include reduced levels of physical activity, the dissipation of load through enlarged joint surfaces, and selection for systemic physiological characteristics that differentiate modern humans from other primates. This study considered the skeletal remains of four behaviorally diverse recent human populations and a large sample of extant primates to assess variation in trabecular bone structure in the human hip joint. Proximal femur trabecular bone structure was quantified from microCT data for 229 individuals from 31 extant primate taxa and 59 individuals from four distinct archaeological human populations representing sedentary agriculturalists and mobile foragers. Analyses of mass-corrected trabecular bone variables reveal that the forager populations had significantly higher bone volume fraction, thicker trabeculae, and consequently lower relative bone surface area compared with the two agriculturalist groups. There were no significant differences between the agriculturalist and forager populations for trabecular spacing, number, or degree of anisotropy. These results reveal a correspondence between human behavior and bone structure in the proximal femur, indicating that more highly mobile human populations have trabecular bone structure similar to what would be expected for wild nonhuman primates of the same body mass. These results strongly emphasize the importance of physical activity and exercise for bone health and the attenuation of age-related bone loss.

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herlin, Maria, E-mail: maria.herlin@ki.se; Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi; Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serummore » levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation results in increased trabecular bone and softer cortical bone. • TCDD does not affect the bones of Ahr{sup –/–} mice.« less

Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification.

PubMed

Osinga, Rik; Di Maggio, Nunzia; Todorov, Atanas; Allafi, Nima; Barbero, Andrea; Laurent, Frédéric; Schaefer, Dirk Johannes; Martin, Ivan; Scherberich, Arnaud

2016-08-01

: Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. Unlike bone marrow-derived stromal cells (also known as bone marrow-derived mesenchymal stromal/stem cells), adipose-derived stromal cells (ASC) have so far failed to form a bone organ by ECO. The goal of the present study was to assess whether priming human ASC to a defined stage of chondrogenesis in vitro allows their autonomous ECO upon ectopic implantation. ASC were cultured either as micromass pellets or into collagen sponges in chondrogenic medium containing transforming growth factor-β3 and bone morphogenetic protein-6 for 4 weeks (early hypertrophic templates) or for two additional weeks in medium supplemented with β-glycerophosphate, l-thyroxin, and interleukin1-β to induce hypertrophic maturation (late hypertrophic templates). Constructs were implanted in vivo and analyzed after 8 weeks. In vitro, ASC deposited cartilaginous matrix positive for glycosaminoglycans, type II collagen, and Indian hedgehog. Hypertrophic maturation induced upregulation of type X collagen, bone sialoprotein, and matrix metalloproteinase13 (MMP13). In vivo, both early and late hypertrophic templates underwent cartilage remodeling, as assessed by MMP13- and tartrate-resistant acid phosphatase-positive staining, and developed bone ossicles, including bone marrow elements, although to variable degrees of efficiency. In situ hybridization for human-specific sequences and staining with a human specific anti-CD146 antibody demonstrated the direct contribution of ASC to bone and stromal tissue formation. In conclusion, despite their debated skeletal progenitor nature, human ASC can generate bone organs through ECO when suitably primed in vitro. Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. This study demonstrated that expanded, human adult adipose-derived stromal cells can generate ectopic bone through ECO, as previously reported for bone marrow stromal cells. This system can be used as a model in a variety of settings for mimicking ECO during development, physiology, or pathology (e.g., to investigate the role of BMPs, their receptors, and signaling pathways). The findings have also translational relevance in the field of bone regeneration, which, despite several advances in the domains of materials and surgical techniques, still faces various limitations before being introduced in the routine clinical practice. ©AlphaMed Press.

Successful subtotal orbitectomy in a cat with osteoma

PubMed Central

Corgozinho, Katia B; Cunha, Simone CS; Siqueira, Ricardo S; Souza, Heloisa JM

2015-01-01

Case summary A 14-year-old Siamese neutered male cat was evaluated for anorexia and a left periorbital mass. Skull radiographic findings showed a well-defined lesion resembling new compact bone formation without destruction. A subtotal orbitectomy was indicated. The tumor was removed intact with a normal tissue margin of at least 1 cm. There were no postsurgical complications. Histopathologic examination revealed an osteoma. The cat returned to normal appetite and activity 15 days after surgery. Six months after surgery, there were no gross signs of recurrence. Relevance and novel information Periorbital tumors are infrequently diagnosed in companion animals and most are malignant. In this case, the diagnosis was orbital osteoma. The most commonly affected bone for osteoma in cats is the mandibular bone; few cases have been identified in orbital bones. Orbital surgery has the potential to be challenging owing to complex anatomy, difficult exposure and the tendency to bleed. Surgical complications are common. In this case, although the disease was advanced, subtotal orbitectomy was successfully performed. PMID:28491397

The Effect of Naturally Occurring Chronic Kidney Disease on the Micro-Structural and Mechanical Properties of Bone

PubMed Central

Meltzer, Hagar; Milrad, Moran; Brenner, Ori; Atkins, Ayelet; Shahar, Ron

2014-01-01

Chronic kidney disease (CKD) is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies) or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD). Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD. PMID:25333360

Combining ergometer exercise and artificial gravity in a compact-radius centrifuge

NASA Astrophysics Data System (ADS)

Diaz, Ana; Trigg, Chris; Young, Laurence R.

2015-08-01

Humans experience physiological deconditioning during space missions, primarily attributable to weightlessness. Some of these adverse consequences include bone loss, muscle atrophy, sensory-motor deconditioning, and cardiovascular alteration, which may lead to orthostatic intolerance when astronauts return to Earth. Artificial gravity could provide a comprehensive countermeasure capable of challenging all the physiological systems at once, particularly if combined with exercise, thereby maintaining overall health during extended exposure to weightlessness. A new Compact Radius Centrifuge (CRC) platform was designed and built on the existing Short Radius Centrifuge (SRC) at the Massachusetts Institute of Technology (MIT). The centrifuge has been constrained to a radius of 1.4 m, the upper radial limit for a centrifuge to fit within an International Space Station (ISS) module without extensive structural alterations. In addition, a cycle ergometer has been added for exercise during centrifugation. The CRC now includes sensors of foot forces, cardiovascular parameters, and leg muscle electromyography. An initial human experiment was conducted on 12 subjects to analyze the effects of different artificial gravity levels (0 g, 1 g, and 1.4 g, measured at the feet) and ergometer exercise intensities (25 W warm-up, 50 W moderate and 100 W vigorous) on the musculoskeletal function as well as motion sickness and comfort. Foot forces were measured during the centrifuge runs, and subjective comfort and motion sickness data were gathered after each session. Preliminary results indicate that ergometer exercise on a centrifuge may be effective in improving musculoskeletal function. The combination is well tolerated and motion sickness is minimal. The MIT CRC is a novel platform for future studies of exercise combined with artificial gravity. This combination may be effective as a countermeasure to space physiological deconditioning.

Radionuclide distribution dynamics in skeletons of beagles fed 90Sr: Correlation with injected 226Ra and 239Pu

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parks, N.J.

Data for the bone-by-bone redistribution of 90Sr in the beagle skeleton are reported for a period of 4000 d following a midgestation-to-540-d-exposure by ingestion. The partitioned clearance model (PCM) that was originally developed to describe bone-by-bone radionuclide redistribution of 226Ra after eight semimonthly injections at ages 435-535 d has been fitted to the 90Sr data. The parameter estimates for the PCM that describe the distribution and clearance of 226Ra after deposition on surfaces following injection and analogous parameter estimates for 90Sr after uniform deposition in the skeleton as a function of Ca mass are given. Fractional compact bone masses permore » bone group (mi,COM) are also predicted by the model and compared to measured values; a high degree of correlation (r = 0.84) is found. Bone groups for which the agreement between the model and experimental values of mi,COM was poor had tissue-to-calcium weight ratios about 1.5 times those for bones that agreed well. Metabolically defined surface in PCM is initial activity fraction per Ca fraction in a given skeletal component for intravenously injected alkaline earth (Sae) radionuclides; comparisons are made to similarly defined surface (Sact) values from 239Pu injection studies. The patterns of Sae and Sact distribution throughout the skeleton are similar.« less

Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells.

PubMed

Nakajima, Kengo; Kunimatsu, Ryo; Ando, Kazuyo; Ando, Toshinori; Hayashi, Yoko; Kihara, Takuya; Hiraki, Tomoka; Tsuka, Yuji; Abe, Takaharu; Kaku, Masato; Nikawa, Hiroki; Takata, Takashi; Tanne, Kazuo; Tanimoto, Kotaro

2018-03-11

Cleft lip and palate is the most common congenital anomaly in the orofacial region. Autogenous iliac bone graft, in general, has been employed for closing the bone defect at the alveolar cleft. However, such iliac bone graft provides patients with substantial surgical and psychological invasions. Consequently, development of a less invasive method has been highly anticipated. Stem cells from human exfoliated deciduous teeth (SHED) are a major candidate for playing a significant role in tissue engineering and regenerative medicine. The aim of this study was to elucidate the nature of bone regeneration by SHED as compared to that of human dental pulp stem cells (hDPSCs) and bone marrow mesenchymal stem cells (hBMSCs). The stems cells derived from pulp tissues and bone marrow were transplanted with a polylactic-coglycolic acid barrier membrane as a scaffold, for use in bone regeneration in an artificial bone defect of 4 mm in diameter in the calvaria of immunodeficient mice. Three-dimensional analysis using micro CT and histological evaluation were performed. Degree of bone regeneration with SHED relative to the bone defect was almost equivalent to that with hDPSCs and hBMSCs 12 weeks after transplantation. The ratio of new bone formation relative to the pre-created bone defect was not significantly different among groups with SHED, hDPSCs and hBMSCs. In addition, as a result of histological evaluation, SHED produced the largest osteoid and widely distributed collagen fibers compared to hDPSCs and hBMSCs groups. Thus, SHED transplantation exerted bone regeneration ability sufficient for the repair of bone defect. The present study has demonstrated that SHED is one of the best candidate as a cell source for the reconstruction of alveolar cleft due to the bone regeneration ability with less surgical invasion. Copyright © 2018 Elsevier Inc. All rights reserved.

Microtomographic imaging in the process of bone modeling and simulation

NASA Astrophysics Data System (ADS)

Mueller, Ralph

1999-09-01

Micro-computed tomography ((mu) CT) is an emerging technique to nondestructively image and quantify trabecular bone in three dimensions. Where the early implementations of (mu) CT focused more on technical aspects of the systems and required equipment not normally available to the general public, a more recent development emphasized practical aspects of micro- tomographic imaging. That system is based on a compact fan- beam type of tomograph, also referred to as desktop (mu) CT. Desk-top (mu) CT has been used extensively for the investigation of osteoporosis related health problems gaining new insight into the organization of trabecular bone and the influence of osteoporotic bone loss on bone architecture and the competence of bone. Osteoporosis is a condition characterized by excessive bone loss and deterioration in bone architecture. The reduced quality of bone increases the risk of fracture. Current imaging technologies do not allow accurate in vivo measurements of bone structure over several decades or the investigation of the local remodeling stimuli at the tissue level. Therefore, computer simulations and new experimental modeling procedures are necessary for determining the long-term effects of age, menopause, and osteoporosis on bone. Microstructural bone models allow us to study not only the effects of osteoporosis on the skeleton but also to assess and monitor the effectiveness of new treatment regimens. The basis for such approaches are realistic models of bone and a sound understanding of the underlying biological and mechanical processes in bone physiology. In this article, strategies for new approaches to bone modeling and simulation in the study and treatment of osteoporosis and age-related bone loss are presented. The focus is on the bioengineering and imaging aspects of osteoporosis research. With the introduction of desk-top (mu) CT, a new generation of imaging instruments has entered the arena allowing easy and relatively inexpensive access to the three-dimensional microstructure of bone, thereby giving bone researchers a powerful tool for the exploration of age-related bone loss and osteoporosis.

Bone tumor location in dogs given skeletal irradiation by {sup 239}Pu or {sup 226}Ra

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lloyd, R.D.; Taylor, G.N.; Miller, S.C.

1997-10-01

Statistical analyses have indicated that there was a significant difference between dogs injected with bone volume-seeking {sup 226} Ra as compared to those given bone surface-seeking {sup 239}Pu with respect to location within the skeleton of 334 radiation-induced primary bone malignancies. Corresponding differences also were event when dogs given bone volume-seeking {sup 90}Sr or bone surface-seeking {sup 241}Am, {sup 228}Th {sup 248,252}Cf, or {sup 224}Ra (which decays mostly on bone surfaces because of its short, 3.6 d half time) were included along with the {sup 226}Ra or {sup 239}Pu, respectively (562 total tumors). Further analysis suggested that higher values ofmore » percent red marrow (M) and bone turnover rate (R) are correlated with increased probability. of tumor appearance at a particular location within the skeleton for the surface seekers. Proportionately higher values of M and R are associated with skeletal sites containing mostly trabecular bone as compared to those with mostly compact (cortical) bone. Coefficients of determination (r{sup 2}) for the relationship between percent of total tumors vs the combination of percent red marrow and turnover rate (= MR) was about 0.7 for the surface seekers but only about 0.1 for the volume seekers. This indicates that the neoplastic effects of surface seekers, but not volume seekers, are associated with the presence of trabecular bone at the various sites of radio nuclide deposition within the skeleton. 10 refs., 3 tabs.« less

Spatial distribution of the trace elements zinc, strontium and lead in human bone tissue.

PubMed

Pemmer, B; Roschger, A; Wastl, A; Hofstaetter, J G; Wobrauschek, P; Simon, R; Thaler, H W; Roschger, P; Klaushofer, K; Streli, C

2013-11-01

Trace elements are chemical elements in minute quantities, which are known to accumulate in the bone. Cortical and trabecular bones consist of bone structural units (BSUs) such as osteons and bone packets of different mineral content and are separated by cement lines. Previous studies investigating trace elements in bone lacked resolution and therefore very little is known about the local concentration of zinc (Zn), strontium (Sr) and lead (Pb) in BSUs of human bone. We used synchrotron radiation induced micro X-ray fluorescence analysis (SR μ-XRF) in combination with quantitative backscattered electron imaging (qBEI) to determine the distribution and accumulation of Zn, Sr, and Pb in human bone tissue. Fourteen human bone samples (10 femoral necks and 4 femoral heads) from individuals with osteoporotic femoral neck fractures as well as from healthy individuals were analyzed. Fluorescence intensity maps were matched with BE images and correlated with calcium (Ca) content. We found that Zn and Pb had significantly increased levels in the cement lines of all samples compared to the surrounding mineralized bone matrix. Pb and Sr levels were found to be correlated with the degree of mineralization. Interestingly, Zn intensities had no correlation with Ca levels. We have shown for the first time that there is a differential accumulation of the trace elements Zn, Pb and Sr in BSUs of human bone indicating different mechanisms of accumulation. © 2013. Published by Elsevier Inc. All rights reserved.

[Remodeling simulation of human femur under bed rest and spaceflight circumstances based on three dimensional finite element analysis].

PubMed

Yang, Wenting; Wang, Dongmei; Lei, Zhoujixin; Wang, Chunhui; Chen, Shanguang

2017-12-01

Astronauts who are exposed to weightless environment in long-term spaceflight might encounter bone density and mass loss for the mechanical stimulus is smaller than normal value. This study built a three dimensional model of human femur to simulate the remodeling process of human femur during bed rest experiment based on finite element analysis (FEA). The remodeling parameters of this finite element model was validated after comparing experimental and numerical results. Then, the remodeling process of human femur in weightless environment was simulated, and the remodeling function of time was derived. The loading magnitude and loading cycle on human femur during weightless environment were increased to simulate the exercise against bone loss. Simulation results showed that increasing loading magnitude is more effective in diminishing bone loss than increasing loading cycles, which demonstrated that exercise of certain intensity could help resist bone loss during long-term spaceflight. At the end, this study simulated the bone recovery process after spaceflight. It was found that the bone absorption rate is larger than bone formation rate. We advise that astronauts should take exercise during spaceflight to resist bone loss.

A Method for Whole Protein Isolation from Human Cranial Bone

PubMed Central

Lyon, Sarah M.; Mayampurath, Anoop; Rogers, M. Rose; Wolfgeher, Donald J.; Fisher, Sean M.; Volchenboum, Samuel L.; He, Tong-Chuan; Reid, Russell R.

2016-01-01

The presence of the dense hydroxyapatite matrix within human bone limits the applicability of conventional protocols for protein extraction. This has hindered the complete and accurate characterization of the human bone proteome thus far, leaving many bone-related disorders poorly understood. We sought to refine an existing method of protein extraction from mouse bone to extract whole proteins of varying molecular weights from human cranial bone. Whole protein was extracted from human cranial suture by mechanically processing samples using a method that limits protein degradation by minimizing heat introduction to proteins. The presence of whole protein was confirmed by western blotting. Mass spectrometry was used to sequence peptides and identify isolated proteins. The data have been deposited to the ProteomeXchange with identifier PXD003215. Extracted proteins were characterized as both intra- and extracellular and had molecular weights ranging from 9.4-629 kDa. High correlation scores among suture protein spectral counts support the reproducibility of the method. Ontology analytics revealed proteins of myriad functions including mediators of metabolic processes and cell organelles. These results demonstrate a reproducible method for isolation of whole protein from human cranial bone, representing a large range of molecular weights, origins and functions. PMID:27677936

Cadmium osteotoxicity in experimental animals: Mechanisms and relationship to human exposures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharyya, Maryka H.

Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure,more » within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.« less

42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

Code of Federal Regulations, 2010 CFR

2010-10-01

... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Pre-Award Disputes § 137.435 Will an...

25 CFR 20.513 - Should Interstate Compacts be used for the placement of children?

Code of Federal Regulations, 2010 CFR

2010-04-01

... children? 20.513 Section 20.513 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES FINANCIAL ASSISTANCE AND SOCIAL SERVICES PROGRAMS Child Assistance Foster Care § 20.513 Should Interstate Compacts be used for the placement of children? Interstate compact agreements should be used when...

77 FR 34989 - Notice of Inventory Completion: U.S. Department of the Interior, Bureau of Indian Affairs...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... search through the survey collection led to the discovery of human bone fragments representing, at... survey collection led to the discovery of three human bone fragments representing, at minimum, one... discovery of one human bone fragment representing, at minimum, one individual. No associated funerary...

Convergence and stress analysis of the homogeneous structure of human femur bone during standing up condition

NASA Astrophysics Data System (ADS)

Izzawati, B.; Daud, R.; Afendi, M.; Majid, M. S. Abdul; Zain, N. A. M.

2017-09-01

Finite element models have been widely used to quantify the stress analysis and to predict the bone fractures of the human body. The present study highlights on the stress analysis of the homogeneous structure of human femur bone during standing up condition. The main objective of this study is to evaluate and understand the biomechanics for human femur bone and to prepare orthotropic homogeneous material models used for FE analysis of the global proximal femur. Thus, it is necessary to investigate critical stress on the human femur bone for future study on implantation of internal fixator and external fixator. The implication possibility to create a valid FE model by simply comparing the FE results with the actual biomechanics structures. Thus, a convergence test was performed by FE model of the femur and the stress analysis based on the actual biomechanics of the human femur bone. An increment of critical stress shows in the femur shaft as the increasing of load on the femoral head and decreasing the pulling force at greater trochanter.

Intrinsic Sensing and Evolving Internal Model Control of Compact Elastic Module for a Lower Extremity Exoskeleton.

PubMed

Wang, Likun; Du, Zhijiang; Dong, Wei; Shen, Yi; Zhao, Guangyu

2018-03-19

To achieve strength augmentation, endurance enhancement, and human assistance in a functional autonomous exoskeleton, control precision, back drivability, low output impedance, and mechanical compactness are desired. In our previous work, two elastic modules were designed for human-robot interaction sensing and compliant control, respectively. According to the intrinsic sensing properties of the elastic module, in this paper, only one compact elastic module is applied to realize both purposes. Thus, the corresponding control strategy is required and evolving internal model control is proposed to address this issue. Moreover, the input signal to the controller is derived from the deflection of the compact elastic module. The human-robot interaction is considered as the disturbance which is approximated by the output error between the exoskeleton control plant and evolving forward learning model. Finally, to verify our proposed control scheme, several experiments are conducted with our robotic exoskeleton system. The experiment shows a satisfying result and promising application feasibility.

Micro-computed tomography assessment of human alveolar bone: bone density and three-dimensional micro-architecture.

PubMed

Kim, Yoon Jeong; Henkin, Jeffrey

2015-04-01

Micro-computed tomography (micro-CT) is a valuable means to evaluate and secure information related to bone density and quality in human necropsy samples and small live animals. The aim of this study was to assess the bone density of the alveolar jaw bones in human cadaver, using micro-CT. The correlation between bone density and three-dimensional micro architecture of trabecular bone was evaluated. Thirty-four human cadaver jaw bone specimens were harvested. Each specimen was scanned with micro-CT at resolution of 10.5 μm. The bone volume fraction (BV/TV) and the bone mineral density (BMD) value within a volume of interest were measured. The three-dimensional micro architecture of trabecular bone was assessed. All the parameters in the maxilla and the mandible were subject to comparison. The variables for the bone density and the three-dimensional micro architecture were analyzed for nonparametric correlation using Spearman's rho at the significance level of p < .05. A wide range of bone density was observed. There was a significant difference between the maxilla and mandible. All micro architecture parameters were consistently higher in the mandible, up to 3.3 times greater than those in the maxilla. The most linear correlation was observed between BV/TV and BMD, with Spearman's rho = 0.99 (p = .01). Both BV/TV and BMD were highly correlated with all micro architecture parameters with Spearman's rho above 0.74 (p = .01). Two aspects of bone density using micro-CT, the BV/TV and BMD, are highly correlated with three-dimensional micro architecture parameters, which represent the quality of trabecular bone. This noninvasive method may adequately enhance evaluation of the alveolar bone. © 2013 Wiley Periodicals, Inc.

Beta 2-Microglobulin: A Novel Therapeutic Target for the Treatment of Human Prostate Cancer Bone Metastasis

DTIC Science & Technology

2009-03-14

H, Sodek J, Zhau HE, Chung LW. Human osteocalcin and bone sialoprotein mediating osteomimicry of prostate cancer cells: role of cAMP-dependent...with mesenchymal phenotype b2-m b2-Microglobulin BSP Bone sialoprotein C4-2 Lineage derivative cells from LNCaP C4-2B C4-2 cells metastasized to bone...OPN) and bone sialoprotein (BSP), and RANKL, collectively allow- ing cancer cells to survive and thrive in the bone microenvironment [7–9]. Previous

Determinants of Microdamage in Elderly Human Vertebral Trabecular Bone

PubMed Central

Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

2013-01-01

Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54–95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

Histomorphometry and cortical robusticity of the adult human femur.

PubMed

Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

2018-01-13

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

Gradual adaptation of bone structure to aquatic lifestyle in extinct sloths from Peru

PubMed Central

Amson, Eli; de Muizon, Christian; Laurin, Michel; Argot, Christine; de Buffrénil, Vivian

2014-01-01

Non-pathological densification (osteosclerosis) and swelling (pachyostosis) of bones are the main modifications affecting the skeleton of land vertebrates (tetrapods) that returned to water. However, a precise temporal calibration of the acquisition of such adaptations is still wanting. Here, we assess the timing of such acquisition using the aquatic sloth Thalassocnus, from the Neogene of the Pisco Formation, Peru. This genus is represented by five species occurring in successive vertebrate-bearing horizons of distinct ages. It yields the most detailed data about the gradual acquisition of aquatic adaptations among tetrapods, in displaying increasing osteosclerosis and pachyostosis through time. Such modifications, reflecting a shift in the habitat from terrestrial to aquatic, occurred over a short geological time span (ca 4 Myr). Otherwise, the bones of terrestrial pilosans (sloths and anteaters) are much more compact than the mean mammalian condition, which suggests that the osteosclerosis of Thalassocnus may represent an exaptation. PMID:24621950

Evolution of bone microanatomy of the tetrapod tibia and its use in palaeobiological inference.

PubMed

Kriloff, A; Germain, D; Canoville, A; Vincent, P; Sache, M; Laurin, M

2008-05-01

Bone microanatomy appears to track changes in various physiological or ecological properties of the individual or the taxon. Analyses of sections of the tibia of 99 taxa show a highly significant (P

The Great Irish Famine: Identifying Starvation in the Tissues of Victims Using Stable Isotope Analysis of Bone and Incremental Dentine Collagen

PubMed Central

Montgomery, Janet

2016-01-01

The major components of human diet both past and present may be estimated by measuring the carbon and nitrogen isotope ratios (δ13C and δ15N) of the collagenous proteins in bone and tooth dentine. However, the results from these two tissues differ substantially: bone collagen records a multi-year average whilst primary dentine records and retains time-bound isotope ratios deriving from the period of tooth development. Recent studies harnessing a sub-annual temporal sampling resolution have shed new light on the individual dietary histories of our ancestors by identifying unexpected radical short-term dietary changes, the duration of breastfeeding and migration where dietary change occurs, and by raising questions regarding factors other than diet that may impact on δ13C and δ15N values. Here we show that the dentine δ13C and δ15N profiles of workhouse inmates dating from the Great Irish Famine of the 19th century not only record the expected dietary change from C3 potatoes to C4 maize, but when used together they also document prolonged nutritional and other physiological stress resulting from insufficient sustenance. In the adults, the influence of the maize-based diet is seen in the δ13C difference between dentine (formed in childhood) and rib (representing an average from the last few years of life). The demonstrated effects of stress on the δ13C and δ15N values will have an impact on the interpretations of diet in past populations even in slow-turnover tissues such as compact bone. This technique also has applicability in the investigation of modern children subject to nutritional distress where hair and nails are unavailable or do not record an adequate period of time. PMID:27508412

Towards modular bone tissue engineering using Ti-Co-doped phosphate glass microspheres: cytocompatibility and dynamic culture studies.

PubMed

Peticone, Carlotta; De Silva Thompson, David; Owens, Gareth J; Kim, Hae-Won; Micheletti, Martina; Knowles, Jonathan C; Wall, Ivan

2017-09-01

The production of large quantities of functional vascularized bone tissue ex vivo still represent an unmet clinical challenge. Microcarriers offer a potential solution to scalable manufacture of bone tissue due to their high surface area-to-volume ratio and the capacity to be assembled using a modular approach. Microcarriers made of phosphate bioactive glass doped with titanium dioxide have been previously shown to enhance proliferation of osteoblast progenitors and maturation towards functional osteoblasts. Furthemore, doping with cobalt appears to mimic hypoxic conditions that have a key role in promoting angiogenesis. This characteristic could be exploited to meet the clinical requirement of producing vascularized units of bone tissue. In the current study, the human osteosarcoma cell line MG-63 was cultured on phosphate glass microspheres doped with 5% mol titanium dioxide and different concentrations of cobalt oxide (0%, 2% and 5% mol), under static and dynamic conditions (150 and 300 rpm on an orbital shaker). Cell proliferation and the formation of aggregates of cells and microspheres were observed over a period of two weeks in all glass compositions, thus confirming the biocompatibility of the substrate and the suitability of this system for the formation of compact micro-units of tissue. At the concentrations tested, cobalt was not found to be cytotoxic and did not alter cell metabolism. On the other hand, the dynamic environment played a key role, with moderate agitation having a positive effect on cell proliferation while higher agitation resulting in impaired cell growth. Finally, in static culture assays, the capacity of cobalt doping to induce vascular endothelial growth factor (VEGF) upregulation by osteoblastic cells was observed, but was not found to increase linearly with cobalt oxide content. In conclusion, Ti-Co phosphate glasses were found to support osteoblastic cell growth and aggregate formation that is a necessary precursor to tissue formation and the upregaulation of VEGF production can potentially support vascularization.

Mesenchymal Stem Cells for Osteochondral Tissue Engineering

PubMed Central

Ng, Johnathan; Bernhard, Jonathan; Vunjak-Novakovic, Gordana

2017-01-01

Summary Mesenchymal stem cells (MSC) are of major interest to regenerative medicine, because of the ease of harvesting from a variety of sources (including bone marrow and fat aspirates) and ability to form a range of mesenchymal tissues, in vitro and in vivo. We focus here on the use of MSCs for engineering of cartilage, bone, and complex osteochondral tissue constructs, using protocols that replicate some aspects of the natural mesodermal development. For engineering of human bone, we discuss some of the current advances, and highlight the use of perfusion bioreactors for supporting anatomically exact human bone grafts. For engineering of human cartilage, we discuss limitations of current approaches, and highlight engineering of stratified, mechanically functional human cartilage interfaced with bone by mesenchymal condensation of MSCs. Taken together, the current advances enable engineering physiologically relevant bone, cartilage and osteochondral composites, and physiologically relevant studies of osteochondral development and disease. PMID:27236665

The skeletal structure of insulin-like growth factor I-deficient mice

NASA Technical Reports Server (NTRS)

Bikle, D.; Majumdar, S.; Laib, A.; Powell-Braxton, L.; Rosen, C.; Beamer, W.; Nauman, E.; Leary, C.; Halloran, B.

2001-01-01

The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.

Experimental vitrification of human compacted morulae and early blastocysts using fine diameter plastic micropipettes.

PubMed

Cremades, N; Sousa, M; Silva, J; Viana, P; Sousa, S; Oliveira, C; Teixeira da Silva, J; Barros, A

2004-02-01

Vitrification of human blastocysts has been successfully applied using grids, straws and cryoloops. We assessed the survival rate of human compacted morulae and early blastocysts vitrified in pipette tips with a smaller inner diameter and solution volume than the previously described open pulled straw (OPS) method. Excess day 5 human embryos (n = 63) were experimentally vitrified in vessels. Embryos were incubated at 37 degrees C with sperm preparation medium (SPM) for 1 min, SPM + 7.5% ethylene glycol (EG)/dimethylsulphoxide (DMSO) for 3 min, and SPM + 16.5% EG + 16.5% DMSO + 0.67 mol/l sucrose for 25 s. They were then aspirated (0.5 microl) into a plastic micropipette tip (0.36 mm inner diameter), exposed to liquid nitrogen (LN(2)) vapour for 2 min before being placed into a pre-cooled cryotube, which was then closed and plunged into LN(2). Embryos were warmed and diluted using 0.33 mol/l and 0.2 mol/l sucrose. The survival rate for compacted morulae was 73% (22/30) and 82% (27/33) for early blastocysts. The survival rates of human compacted morulae and early blastocysts after vitrification with this simple technique are similar to those reported in the literature achieved by slow cooling and other vitrification protocols.

Bone morphogenetic protein (BMP)1-3 enhances bone repair.

PubMed

Grgurevic, Lovorka; Macek, Boris; Mercep, Mladen; Jelic, Mislav; Smoljanovic, Tomislav; Erjavec, Igor; Dumic-Cule, Ivo; Prgomet, Stefan; Durdevic, Dragan; Vnuk, Drazen; Lipar, Marija; Stejskal, Marko; Kufner, Vera; Brkljacic, Jelena; Maticic, Drazen; Vukicevic, Slobodan

2011-04-29

Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) regulate morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8. We have recently discovered that BMP1-3 isoform of the Bmp-1 gene circulates in the human plasma and is significantly increased in patients with acute bone fracture. We hypothesized that circulating BMP1-3 might have an important role in bone repair and serve as a novel bone biomarker. When administered systemically to rats with a long bone fracture and locally to rabbits with a critical size defect of the ulna, recombinant human BMP1-3 enhanced bone healing. In contrast, neutralization of the endogenous BMP1-3 by a specific polyclonal antibody delayed the bone union. Invitro BMP1-3 increased the expression of collagen type I and osteocalcin in MC3T3-E(1) osteoblast like cells, and enhanced the formation of mineralized bone nodules from bone marrow mesenchymal stem cells. We suggest that BMP1-3 is a novel systemic regulator of bone repair. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

NASA Technical Reports Server (NTRS)

Halloran, B.; Weider, T.; Morey-Holton, E.

1999-01-01

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Osteoinductive effect of bone bank allografts on human osteoblasts in culture.

PubMed

de la Piedra, Concepción; Vicario, Carlos; de Acuña, Lucrecia Rodríguez; García-Moreno, Carmen; Traba, Maria Luisa; Arlandis, Santiago; Marco, Fernando; López-Durán, Luis

2008-02-01

Incorporation of a human bone allograft requires osteoclast activity and growth of recipient osteoblasts. The aim of this work was to study the effects produced by autoclavated and -80 degrees C frozen bone allografts on osteoblast proliferation and synthesis of interleukin 6 (IL6), activator of bone resorption, aminoterminal propeptide of procollagen I (PINP), marker of bone matrix formation, and osteoprotegerin (OPG), inhibitor of osteoclast activity and differentiation. Allografts were obtained from human femoral heads. Human osteoblasts were cultured in the presence (problem group) or in the absence (control group) of allografts during 15 days. Allografts produced a decrease in osteoblast proliferation in the first week of the experiment, and an increase in IL6 mRNA, both at 3 h and 2 days, and an increase in the IL6 released to the culture medium the second day of the experiment. We found a decrease in OPG released to the culture on the 2nd and fourth days. These results suggest an increase in bone resorption and a decrease in bone formation in the first week of the experiment. In the second week, allografts produced an increase in osteoblast proliferation and PINP release to the culture medium, indicating an increase in bone formation; an increase in OPG released to the culture medium, which would indicate a decrease in bone resorption; and a decrease in IL6, indicating a decrease in bone resorption stimulation. These results demonstrate that autoclavated and -80 degrees C frozen bone allografts produce in bone environment changes that regulate their own incorporation to the recipient bone.

Ethanol inhibits human bone cell proliferation and function in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friday, K.E.; Howard, G.A.

1991-06-01

The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantlymore » reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol.« less

[Disruption of the arteria nutricia tibiae by reamed and unreamed intramedullary nailing. Study of the vascular architecture of the human tibial intramedullary cavity].

PubMed

Paar, O; mon O'Dey, D; Magin, M N; Prescher, A

2000-01-01

By reason of the pseudarthrotic healing of fractures due to vascular complications after reamed and unreamed intramedullary nailing, the intraosseous course and branching of the tibial nutrient artery and its impairment by nailing procedures needs an actual analysis. The nutrient vessel of 24 tibiae taken from fresh corpses were prepared by injection of Technovit and lead oxide. After this procedure the medullary cavities of 12 bones were opened by a frontal cut. These specimens were subjected to routine maceration. The other 12 tibiae were naed with the unreamed (6) and the reamed nailing (6) techniques. X-rays were also taken routinely. After penetration of the tibial compact bone the main trunk of the nutrient vessel runs through a perforated osseous tunnel (pars tecta arteriae nutriciae tibiae). At its end the vessel divides into a descending branch (obligate) and two ascending branches (facultative). The descending branch lies near to the centromedial region of the medullary cavity which is termed as the pars liberal arteriae nutriciae tibiae. All branches pass through supporting horizontal osseous lamellas. Due to this topography the reamed nailing technique destroyed the nutrient vessel completely in all specimens. In contrast to this observation the unreamed nailing destroyed the vessel completely only in 1 (16.7%) and partially in 3 (50%) bones; 2 (33.3%) specimens exhibited no destruction of the vessel. The unreamed as well as the reamed nailing technique can destroy the intramedullary course of the tibial nutrient artery. Fractures as well as displacement osteotomies or corticotomies are able to diminish the medullary blood supply seriously, if they are localised within the area of the tactic an of the tibial nutrient artery.

Post Processing and Biological Evaluation of the Titanium Scaffolds for Bone Tissue Engineering.

PubMed

Wysocki, Bartłomiej; Idaszek, Joanna; Szlązak, Karol; Strzelczyk, Karolina; Brynk, Tomasz; Kurzydłowski, Krzysztof J; Święszkowski, Wojciech

2016-03-15

Nowadays, post-surgical or post-accidental bone loss can be substituted by custom-made scaffolds fabricated by additive manufacturing (AM) methods from metallic powders. However, the partially melted powder particles must be removed in a post-process chemical treatment. The aim of this study was to investigate the effect of the chemical polishing with various acid baths on novel scaffolds' morphology, porosity and mechanical properties. In the first stage, Magics software (Materialise NV, Leuven, Belgium) was used to design a porous scaffolds with pore size equal to (A) 200 µm, (B) 500 µm and (C) 200 + 500 µm, and diamond cell structure. The scaffolds were fabricated from commercially pure titanium powder (CP Ti) using a SLM50 3D printing machine (Realizer GmbH, Borchen, Germany). The selective laser melting (SLM) process was optimized and the laser beam energy density in range of 91-151 J/mm³ was applied to receive 3D structures with fully dense struts. To remove not fully melted titanium particles the scaffolds were chemically polished using various HF and HF-HNO₃ acid solutions. Based on scaffolds mass loss and scanning electron (SEM) observations, baths which provided most uniform surface cleaning were proposed for each porosity. The pore and strut size after chemical treatments was calculated based on the micro-computed tomography (µ-CT) and SEM images. The mechanical tests showed that the treated scaffolds had Young's modulus close to that of compact bone. Additionally, the effect of pore size of chemically polished scaffolds on cell retention, proliferation and differentiation was studied using human mesenchymal stem cells. Small pores yielded higher cell retention within the scaffolds, which then affected their growth. This shows that in vitro cell performance can be controlled to certain extent by varying pore sizes.

Post Processing and Biological Evaluation of the Titanium Scaffolds for Bone Tissue Engineering

PubMed Central

Wysocki, Bartłomiej; Idaszek, Joanna; Szlązak, Karol; Strzelczyk, Karolina; Brynk, Tomasz; Kurzydłowski, Krzysztof J.; Święszkowski, Wojciech

2016-01-01

Nowadays, post-surgical or post-accidental bone loss can be substituted by custom-made scaffolds fabricated by additive manufacturing (AM) methods from metallic powders. However, the partially melted powder particles must be removed in a post-process chemical treatment. The aim of this study was to investigate the effect of the chemical polishing with various acid baths on novel scaffolds’ morphology, porosity and mechanical properties. In the first stage, Magics software (Materialise NV, Leuven, Belgium) was used to design a porous scaffolds with pore size equal to (A) 200 µm, (B) 500 µm and (C) 200 + 500 µm, and diamond cell structure. The scaffolds were fabricated from commercially pure titanium powder (CP Ti) using a SLM50 3D printing machine (Realizer GmbH, Borchen, Germany). The selective laser melting (SLM) process was optimized and the laser beam energy density in range of 91–151 J/mm3 was applied to receive 3D structures with fully dense struts. To remove not fully melted titanium particles the scaffolds were chemically polished using various HF and HF-HNO3 acid solutions. Based on scaffolds mass loss and scanning electron (SEM) observations, baths which provided most uniform surface cleaning were proposed for each porosity. The pore and strut size after chemical treatments was calculated based on the micro-computed tomography (µ-CT) and SEM images. The mechanical tests showed that the treated scaffolds had Young’s modulus close to that of compact bone. Additionally, the effect of pore size of chemically polished scaffolds on cell retention, proliferation and differentiation was studied using human mesenchymal stem cells. Small pores yielded higher cell retention within the scaffolds, which then affected their growth. This shows that in vitro cell performance can be controlled to certain extent by varying pore sizes. PMID:28773323

Quantification of Sodium (Na) in Bone with in Vivo Neutron Activation Analysis (IVNAA) and Its Implications on Na Retention Studies

NASA Astrophysics Data System (ADS)

Coyne, Mychaela

The locations of Na storage and its exchange mechanisms in different tissues in the body are not well known. This information is important for understanding the impact of Na intake, absorption, and retention on human health, especially on the risk of developing chronic diseases like hypertension. In order to non-invasively quantify Na in bone, a compact deuterium-deuterium (DD) neutron generator-based IVNAA system was developed for use in Na nutrition studies. This thesis will first discuss the optimization of the system using MCNP to maximize the thermal neutron flux inside the irradiation cave while limiting radiation exposure to the hand and the whole body. With optimized assembly in place, an animal study was conducted to investigate the storage and exchange of Na in the body. The right posterior legs of two live pigs, one on a low Na diet and one on a high Na diet, were irradiated inside the customized assembly and then measured with a 100% high efficiency high purity germanium detector (HPGe). The results show that the difference in concentration between the pigs on high vs low Na diets was distinguishable with the system. Analysis also shows rapid exchange of Na in the leg during the first 2 hour measurements (with an exchange decay time of 1.3 hours) while the exchange was minimal at the second and third 2 hour measurements, taken 7 and 21 hours post irradiation. With these results, we conclude there is a non or low exchangeable compartment (likely to be bone) for Na storage and that the DD neutron generator-based IVNAA is a useful method in Na nutrition studies.

Extracellular matrix components and culture regimen selectively regulate cartilage formation by self-assembling human mesenchymal stem cells in vitro and in vivo.

PubMed

Ng, Johnathan; Wei, Yiyong; Zhou, Bin; Burapachaisri, Aonnicha; Guo, Edward; Vunjak-Novakovic, Gordana

2016-12-09

Cartilage formation from self-assembling mesenchymal stem cells (MSCs) in vitro recapitulate important cellular events during mesenchymal condensation that precedes native cartilage development. The goal of this study was to investigate the effects of cartilaginous extracellular matrix (ECM) components and culture regimen on cartilage formation by self-assembling human MSCs in vitro and in vivo. Human bone marrow-derived MSCs (hMSCs) were seeded and compacted in 6.5-mm-diameter transwell inserts with coated (type I, type II collagen) or uncoated (vehicle) membranes, at different densities (0.5 × 10 6 , 1.0 × 10 6 , 1.5 × 10 6 per insert). Pellets were formed by aggregating hMSCs (0.25 × 10 6 ) in round-bottomed wells. All tissues were cultured for up to 6 weeks for in vitro analyses. Discs (cultured for 6, 8 or 10 weeks) and pellets (cultured for 10 weeks) were implanted subcutaneously in immunocompromised mice to evaluate the cartilage stability in vivo. Type I and type II collagen coatings enabled cartilage disc formation from self-assembling hMSCs. Without ECM coating, hMSCs formed dome-shaped tissues resembling the pellets. Type I collagen, expressed in the prechondrogenic mesenchyme, improved early chondrogenesis versus type II collagen. High seeding density improved cartilage tissue properties but resulted in a lower yield of disc formation. Discs and pellets exhibited compositional and organizational differences in vitro and in vivo. Prolonged chondrogenic induction of the discs in vitro expedited endochondral ossification in vivo. The outcomes of cartilage tissues formed from self-assembling MSCs in vitro and in vivo can be modulated by the control of culture parameters. These insights could motivate new directions for engineering cartilage and bone via a cartilage template from self-assembling MSCs.

Surprising origin of two carved bones donated to the Buchenwald Memorial Museum.

PubMed

Gapert, René

2018-03-28

Unidentified bones were donated to the Buchenwald Memorial Museum in Weimar, Germany. The donor thought the bones may have belonged to internees of the concentration camp and had been decoratively carved by camp personnel. Non-destructive forensic anthropological examination was carried out on the bones to identify their possible origin. Comparative human and non-human bones samples were used to determine the provenance of the bones and the anatomical region they may have come from. Literature and internet searches were conducted to trace the origin of the carved motifs on the bones. The bones were determined to belong to the lower limb region of bovids. The carvings were found to correspond with those of existing bone examples found in some museums in the UK. They were traced to German prisoners of war dating to the First World War. An in-depth examination of the donated bones revealed their non-human provenance. It further showed that no link existed between the bones, internees of the concentration camp, and the time of the camp's existence. It was discovered that they belonged to the period 1914-1918 and form an important part of German prisoner of war history in the UK.

Promising efficacy of Escherichia coli recombinant human bone morphogenetic protein-2 in collagen sponge for ectopic and orthotopic bone formation and comparison with mammalian cell recombinant human bone morphogenetic protein-2.

PubMed

Kim, In Sook; Lee, Eui Nam; Cho, Tae Hyung; Song, Yun Mi; Hwang, Soon Jung; Oh, Ji Hye; Park, Eun Kyung; Koo, Tai Young; Seo, Young-Kwon

2011-02-01

Nonglycosylated recombinant human bone morphogenetic protein (rhBMP)-2 prepared in Escherichia coli (E. coli rhBMP-2) has recently been considered as an alternative to mammalian cell rhBMP-2. However, its clinical use is still limited owing to lack of evidence for osteogenic activity comparable with that of mammalian cell rhBMP-2 via microcomputed tomography-based analysis. Therefore, this study aimed to evaluate the ability of E. coli rhBMP-2 in absorbable collagen sponge to form ectopic and orthotopic bone and to compare it to that of mammalian rhBMP-2. In vitro investigation was performed to study osteoblast differentiation of human mesenchymal stromal cells. Both types of rhBMP-2 enhanced proliferation, alkaline phosphatase activity, and matrix mineralization of human mesenchymal stromal cells at similar levels. Similar tendencies were observed in microcomputed tomography analysis, which determined bone volume, fractional bone volume, trabecular thickness, trabecular separation, bone mineral density, and other characteristics. Histology from an in vivo osteoinductivity test and from a rat calvarial defect model demonstrated a dose-dependent increase in local bone formation. The E. coli rhBMP-2 group (5 μg) not only induced complete regeneration of an 8-mm critical-sized defect at 4 weeks, but also led to new bone with the same bone mineral density as normal bone at 8 weeks, with the same efficiency as that of mammalian cell rhBMP-2 (5 μg). These uniformly favorable results provide evidence that the osteogenic activity of E. coli rhBMP-2 is not inferior to that of mammalian cell rhBMP-2 despite its low solubility and lack of gylcosylation. These results suggest that the application of E. coli rhBMP-2 in absorbable collagen sponge may be a promising equivalent to mammalian cell rhBMP-2 in bone tissue engineering.

Tissue engineering skeletal muscle for orthopaedic applications

NASA Technical Reports Server (NTRS)

Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

2002-01-01

With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

A clinical investigation of demineralized bone matrix putty for treatment of periodontal bony defects in humans.

PubMed

Banjar, Arwa Ahmed; Mealey, Brian L

2013-01-01

The goal of this study was to evaluate the effectiveness of demineralized bone matrix (DBM) putty, consisting of demineralized human bone allograft matrix in a carrier of bovine collagen and alginate, for the treatment of periodontal defects in humans. Twenty subjects with at least one site having a probing depth ≥ 6 mm and radiographic evidence of bony defect depth > 3 mm were included. The infrabony defects were grafted with DBM putty bone graft. The following clinical parameters were assessed at baseline and 6 months posttreatment: probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). Bone fill was evaluated using transgingival probing and standardized radiographs taken at baseline and 6 months posttreatment. The 6-month evaluation showed a significant PD reduction of 3.27 ± 1.67 mm and clinical attachment gain of 2.27 ± 1.74 mm. Bone sounding measurements showed a mean clinical bone defect fill of 2.93 ± 1.87 mm and a mean radiographic bone fill of 2.55 ± 2.31 mm. The use of DBM putty was effective for treatment of periodontal bony defects in humans. Significant improvement in CAL, PD, and bone fill was observed at 6 months compared to baseline.

Low-cost compact thermal imaging sensors for body temperature measurement

NASA Astrophysics Data System (ADS)

Han, Myung-Soo; Han, Seok Man; Kim, Hyo Jin; Shin, Jae Chul; Ahn, Mi Sook; Kim, Hyung Won; Han, Yong Hee

2013-06-01

This paper presents a 32x32 microbolometer thermal imaging sensor for human body temperature measurement. Waferlevel vacuum packaging technology allows us to get a low cost and compact imaging sensor chip. The microbolometer uses V-W-O film as sensing material and ROIC has been designed 0.35-um CMOS process in UMC. A thermal image of a human face and a hand using f/1 lens convinces that it has a potential of human body temperature for commercial use.

Integrin αMβ2 is differently expressed by subsets of human osteoclast precursors and mediates adhesion of classical monocytes to bone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sprangers, Sara, E-mail: s.l.sprangers@acta.nl; Schoenmaker, Ton, E-mail: t.schoenmaker@acta.nl; Department of Periodontology, Academic Centre for Dentistry Amsterdam

Bone-degrading osteoclasts are formed through fusion of their monocytic precursors. In the population of human peripheral blood monocytes, three distinct subsets have been identified: classical, intermediate and non-classical monocytes. We have previously shown that when the monocyte subsets are cultured on bone, significantly more osteoclasts are formed from classical monocytes than from intermediate or non-classical monocytes. Considering that this difference does not exist when monocyte subsets are cultured on plastic, we hypothesized that classical monocytes adhere better to the bone surface compared to intermediate and non-classical monocytes. To investigate this, the different monocyte subsets were isolated from human peripheral bloodmore » and cultured on slices of human bone in the presence of the cytokine M-CSF. We found that classical monocytes adhere better to bone due to a higher expression of the integrin αMβ2 and that their ability to attach to bone is significantly decreased when the integrin is blocked. This suggests that integrin αMβ2 mediates attachment of osteoclast precursors to bone and thereby enables the formation of osteoclasts.« less

Cross-sectional geometry of Pecos Pueblo femora and tibiae--a biomechanical investigation: II. Sex, age, side differences.

PubMed

Ruff, C B; Hayes, W C

1983-03-01

Intra-populational variation in cross-sectional geometric properties of the femur and tibia are investigated in the Pecos Pueblo skeletal sample. Sex differences in geometric parameters suggest that male lower limb bones are more adapted for A-P bending, females for M-L bending. Proposed explanations for this finding include sexual dimorphism in pelvic structure and culturally prescribed sex-related activities at Pecos. With aging, both males and females undergo endosteal resorption and cortical thinning, greater among females. Both sexes also demonstrate an increase with age in subperiosteal area and second moments of area, supporting results reported in some studies of modern population samples. Sex and site-specific remodeling of the femur and tibia with aging also occur. These localized remodeling changes appear to selectively conserve more compact cortical bone in areas of high mechanical stress. Side differences in cross-sectional geometric properties indicate that left lower limb bones are generally larger than right lower limb bones, with asymmetry greater among females. In particular, left femora and tibiae are relatively stronger in A-P bending, again more so in females.

A single scan skeletonization algorithm: application to medical imaging of trabecular bone

NASA Astrophysics Data System (ADS)

Arlicot, Aurore; Amouriq, Yves; Evenou, Pierre; Normand, Nicolas; Guédon, Jean-Pierre

2010-03-01

Shape description is an important step in image analysis. The skeleton is used as a simple, compact representation of a shape. A skeleton represents the line centered in the shape and must be homotopic and one point wide. Current skeletonization algorithms compute the skeleton over several image scans, using either thinning algorithms or distance transforms. The principle of thinning is to delete points as one goes along, preserving the topology of the shape. On the other hand, the maxima of the local distance transform identifies the skeleton and is an equivalent way to calculate the medial axis. However, with this method, the skeleton obtained is disconnected so it is required to connect all the points of the medial axis to produce the skeleton. In this study we introduce a translated distance transform and adapt an existing distance driven homotopic algorithm to perform skeletonization with a single scan and thus allow the processing of unbounded images. This method is applied, in our study, on micro scanner images of trabecular bones. We wish to characterize the bone micro architecture in order to quantify bone integrity.

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

PubMed

Kim, Beom-Jun; Kwak, Mi Kyung; Ahn, Seong Hee; Kim, Hyeonmok; Lee, Seung Hun; Song, Kee-Ho; Suh, Sunghwan; Kim, Jae Hyeon; Koh, Jung-Min

2017-08-01

Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. To clarify the link between the sympathetic nervous system and the skeleton in humans. Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption. Copyright © 2017 Endocrine Society

Mesenchymal stem cells for bone repair and metabolic bone diseases.

PubMed

Undale, Anita H; Westendorf, Jennifer J; Yaszemski, Michael J; Khosla, Sundeep

2009-10-01

Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases.

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations

PubMed Central

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-01-01

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. PMID:24975579

[Musculoskeletal rehabilitation and bone. Musculoskeletal response to human space flight and physical countermeasures].

PubMed

Ohshima, Hiroshi

2010-04-01

The assembly of the Japanese Experiment Module "Kibo" to international space station was completed in 2009 and Koichi Wakata became the first Japanese station astronaut who spent more than 4 months in the station. Bone and muscle losses are significant medical concerns for long duration human space flight. Effective countermeasure program for bone loss and muscle atrophy is necessary to avoid post flight bone fracture and joint sprain after landing. The musculoskeletal response to human space flight and current physical countermeasure program for station astronauts are described.

Dynamic Mechanical Testing Techniques for Cortical and Cancellous Bone

NASA Astrophysics Data System (ADS)

Cloete, Trevor

2017-06-01

Bone fracture typically occurs as an impact loading event (sporting accidents, vehicle collisions), the simulation of which requires in-depth understanding of dynamic bone behavior. Bone is a natural composite material with a complex multi length-scale hierarchical microstructure. At a macroscopic level, it is classified into hard/compact cortical bone and soft/spongy cancellous (trabecular) bone, though both are low-impedance materials relative to steels. Cortical bone is predominant in long bones, while in complex bone geometries (joints, flat bones) a cancellous bone core supports a thin cortical shell. Bone has primarily been studied at quasi-static strain rates (ɛ˙ < 1s-1), with some dynamic studies (300s-1 <ɛ˙ < 3000s-1), but rarely at intermediate strain rates (ISR) (1s-1 <ɛ˙ < 100s-1). The data shows bone to be viscoelastic, which suggests that more dynamic and ISR data is required. Furthermore, bone exhibits quasi-brittle failure, with interrupted quasi-static tests revealing a strong microstructure dependence. However, bone specimens are typically destroyed during dynamic tests, leading to a lack of dynamic microstructural damage investigations. In this paper, a short overview of dynamic bone testing is presented to give context to the challenges of testing low impedance, strain-rate dependent, non-linear, visco-elastic-brittle materials. Recent state-of-the-art experimental developments in dynamic bone testing are reviewed, with emphasis on pulse shaping, momentum trapping and ISR testing. These techniques allow for dynamic bone testing at small strains and near-constant strain rates with intact specimen recovery. The results are compared to those obtained with varying strain rate tests. Interrupted dynamic test results with microstructural analysis of the recovered specimens are presented and discussed. The paper concludes with a discussion of the experimental and modeling challenges that lie ahead in the field of dynamic bone behavior. The financial assistance of the National Research Foundation and the University of Cape Town towards this research is hereby acknowledged. Opinions expressed and conclusions arrived at are those of the author alone.

Comparison of Bone Grafts From Various Donor Sites in Human Bone Specimens.

PubMed

Kamal, Mohammad; Gremse, Felix; Rosenhain, Stefanie; Bartella, Alexander K; Hölzle, Frank; Kessler, Peter; Lethaus, Bernd

2018-05-14

The objective of the current study was to compare the three-dimensional (3D) morphometric microstructure in human cadaveric bone specimens taken from various commonly utilized donor sites for autogenous bone grafting. Autogenous bone grafts can be harvested from various anatomic sites and express heterogeneous bone quality with a specific 3D microstructure for each site. The long-term structural integrity and susceptibility to resorption of the graft depend on the selected donor bone. Micro-computed tomography generates high-resolution datasets of bone structures and calcifications making this modality versatile for microarchitecture analysis and quantification of the bone. Six bone specimens, 10 mm in length, where anatomically possible, were obtained from various anatomical sites from 10 human dentate cadavers (4 men, 6 women, mean age 69.5 years). Specimens were scanned using a micro-computed tomography device and volumetrically reconstructed. A virtual cylindrical inclusion was reconstructed to analyze the bone mineral density and structural morphometric analysis using bone indices: relative bone volume, surface density, trabecular thicknesses, and trabecular separation. Calvarial bone specimens showed the highest mineral density, followed by the chin, then mandibular ramus then the tibia, whereas iliac crest and maxillary tuberosity had lower bone mineral densities. The pairwise comparison revealed statistically significant differences in the bone mineral density and relative bone volume index in the calvaria, mandibular ramus, mandibular symphysis groups when compared with those in the iliac crest and maxillary tuberosity, suggesting higher bone quality in the former groups than in the latter; tibial specimens expressed variable results.

The role of the collaborative functions of the composite structure of organic and inorganic constituents and their influence on the electrical properties of human bone.

PubMed

Kohata, Kazuhiro; Itoh, Soichiro; Horiuchi, Naohiro; Yoshioka, Taro; Yamashita, Kimihiro

2016-08-12

The electrical potential, which is generated in bone by collagen displacement, has been well documented. However, the role of mineral crystals in bone piezoelectricity has not yet been elucidated. We examined the mechanism that the composite structure of organic and inorganic constituents and their collaborative functions play an important role in the electrical properties of human bone. The electrical potential and bone structure were evaluated using thermally stimulated depolarized current (TSDC) and micro computed tomography, respectively. After electrical polarization of bone specimens, the stored electrical charge was calculated using TSDC measurements. The CO3/PO4 peak ratio was calculated using attenuated total reflection to compare the content of carbonate ion in the bone specimens. The TSDC curve contained 3 peaks at 100, 300 and 500°C, which were classified into 4 patterns. The CO3/PO4 peak ratio positively correlated with the stored charges at approximately 300°C in the polarized bone. There was a positive correlation between the stored bone charge and the bone mineral density only. It is suggested that the peak at 300°C is attributed to carbonate apatite and the total bone mass of human bone, not the three-dimensional structure, affects the stored charge.

A tissue engineering solution for segmental defect regeneration in load-bearing long bones.

PubMed

Reichert, Johannes C; Cipitria, Amaia; Epari, Devakara R; Saifzadeh, Siamak; Krishnakanth, Pushpanjali; Berner, Arne; Woodruff, Maria A; Schell, Hanna; Mehta, Manav; Schuetz, Michael A; Duda, Georg N; Hutmacher, Dietmar W

2012-07-04

The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep--a model closely resembling human bone formation and structure--were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

Quantitative in vivo assessment of bone microarchitecture in the human knee using HR-pQCT.

PubMed

Kroker, Andres; Zhu, Ying; Manske, Sarah L; Barber, Rhamona; Mohtadi, Nicholas; Boyd, Steven K

2017-04-01

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel imaging modality capable of visualizing bone microarchitecture in vivo at human peripheral sites such as the distal radius and distal tibia. This research has extended the technology to provide a non-invasive assessment of bone microarchitecture at the human knee by establishing new hardware, imaging protocols and data analysis. A custom leg holder was developed to stabilize a human knee centrally within a second generation HR-pQCT field of view. Five participants with anterior cruciate ligament reconstructions had their knee joint imaged in a continuous scan of 6cm axially. The nominal isotropic voxel size was 60.7μm. Bone mineral density and microarchitecture were assessed within the weight-bearing regions of medial and lateral compartments of the knee at three depths from the weight-bearing articular bone surface, including both the cortical and trabecular bone regions. Scan duration was approximately 18min per knee and produced 5GB of projection data and 10GB of reconstructed image data (2304×2304 image matrix, 1008 slices). Motion during the scan was minimized by the leg holder and was similar in magnitude as a scan of the distal tibia. Bone mineral density and microarchitectural parameters were assessed for 16 volumes of interest in the tibiofemoral joint. This is a new non-invasive in vivo assessment tool for bone microarchitecture in the human knee that provides an opportunity to gain insight into normal, injured and surgically reconstructed human knee bone architecture in cross-sectional or longitudinal studies. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Drilling force and temperature of bone under dry and physiological drilling conditions

NASA Astrophysics Data System (ADS)

Xu, Linlin; Wang, Chengyong; Jiang, Min; He, Huiyu; Song, Yuexian; Chen, Hanyuan; Shen, Jingnan; Zhang, Jiayong

2014-11-01

Many researches on drilling force and temperature have been done with the aim to reduce the labour intensiveness of surgery, avoid unnecessary damage and improve drilling quality. However, there has not been a systematic study of mid- and high-speed drilling under dry and physiological conditions(injection of saline). Furthermore, there is no consensus on optimal drilling parameters. To study these parameters under dry and physiological drilling conditions, pig humerus bones are drilled with medical twist drills operated using a wide range of drilling speeds and feed rates. Drilling force and temperature are measured using a YDZ-II01W dynamometer and a NEC TVS-500EX thermal infrared imager, respectively, to evaluate internal bone damage. To evaluate drilling quality, bone debris and hole morphology are observed by SEM(scanning electron microscopy). Changes in drilling force and temperature give similar results during drilling such that the value of each parameter peaks just before the drill penetrates through the osteon of the compact bone into the trabeculae of the spongy bone. Drilling temperatures under physiological conditions are much lower than those observed under dry conditions, while a larger drilling force occurs under physiological conditions than dry conditions. Drilling speed and feed rate have a significant influence on drilling force, temperature, bone debris and hole morphology. The investigation of the effect of drilling force and temperature on internal bone damage reveals that a drilling speed of 4500 r/min and a feed rate of 50 mm/min are recommended for bone drilling under physiological conditions. Drilling quality peaks under these optimal parameter conditions. This paper proposes the optimal drilling parameters under mid- and high-speed surgical drilling, considering internal bone damage and drilling quality, which can be looked as a reference for surgeons performing orthopedic operations.

Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

NASA Technical Reports Server (NTRS)

Sibonga, Jean D.

2010-01-01

This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

[Effects of cuttlefish bone-bone morphogenetic protein composite material on osteogenesis and revascularization of bone defect in rats].

PubMed

Liu, Yuan; Yu, Jiang; Bai, Jie; Gu, Jin-song; Cai, Bin; Zhou, Xia

2013-12-01

To study the effects of cuttlefish bone-bone morphogenetic protein (BMP) composite material on osteogenesis and revascularization of bone defect in rats. The cuttlefish bone was formed into cylinder with the diameter of about 5 mm and height of about 2 mm after the shell was removed, and then it was soaked in the recombinant human BMP 2 to make a cuttlefish bone-BMP (CBB) composite material. Thirty SD rats, with a defect of skull in every rat, were divided into the CBB and pure cuttlefish bone (PCB) groups according to the random number table, with 15 rats in each group. The rats in the group CBB and group PCB were transplanted with the corresponding material to repair the skull defect. At post transplantation week (PTW) 4, 6, and 8, 5 rats from every group were sacrificed by exsanguination, and ink perfusion was performed. One day later, all the transplants and part of the skull surrounding the defect were harvested, and general observation was conducted at the same time. The specimens were paraffin sectioned for HE staining and Masson staining. The area of microvessel and the area of newborn bone were observed and analyzed through histopathological techniques and image collection system. Data were processed with the analysis of variance of factorial design and LSD test. The correlation between the area of microvessel and the area of newborn bone of the group CBB was analyzed with Pearson correlation analysis. (1) The general observation of the transplant region showed that the transplants were encapsulated by a capsule of fibrous connective tissue. The texture of capsule was soft and relatively thick at PTW 4. The texture was tenacious and thin, but rather compact at PTW 6 and 8. The transplants became gelatinous at PTW 4, and similar to the cartilage tissue at PTW 6 and 8. (2) Histological observation showed that the structure of the transplants in two groups was damaged at PTW 4. A moderate quantity of inflammatory cell infiltration could be observed. The amounts of the primary bone trabeculae and microvessels in group CBB were more abundant than those of group PCB, while the number of osteoclasts was less than those of group PCB. At PTW 6, the inflammatory cell infiltration in the transplants in both groups decreased obviously, the cuttlefish bone was found to be further degraded, and the number of newborn microvessels was increased. There were mature bone trabeculae around the transplants in both groups. And there were also mature bone trabeculae in the degraded CBB in group CBB. At PTW 8, the inflammatory reaction in the transplants in both groups disappeared; there were more mature bone trabeculae; the structure of the cuttlefish bone was found to be damaged basically. Bone trabeculae in group PCB were found around the transplant, while the bone trabeculae could be observed not only around the transplant but also in the degraded CBB in group CBB. The amount of the microvessels in group CBB was still larger than that of group PCB. (3) From PTW 4 to 8, the area of microvessel in group CBB [(63 ± 4), ( 136 ± 36), ( 347 ± 31) µm(2)] was larger than that in group PCB [(44 ± 7), (73 ± 4), (268 ± 42) µm(2), P < 0.05 or P < 0.01]. From PTW 4 to 8, the area of newborn bone in group CBB [(236 ± 26), (339 ± 42), (553 ± 40) µm(2)] was larger than that in group PCB [(137 ± 15), (243 ± 21), (445 ± 29) µm(2), with P values all below 0.01]. (4) The relation between the area of microvessel and the area of newborn bone was significantly positive (r = 0.948, P = 0.001). The CBB may exert good effect on osteogenesis and vascularization of rats with bone defect. It is a good three dimensional scaffold in bone tissue engineering.

Morphological Characterization of the Frontal and Parietal Bones of the Human Skull

DTIC Science & Technology

2017-03-01

ARL-TR- 7962 ● MAR 2017 US Army Research Laboratory Morphological Characterization of the Frontal and Parietal Bones of the...Army Research Laboratory Morphological Characterization of the Frontal and Parietal Bones of the Human Skull by Stephen L Alexander SURVICE...

Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis

PubMed Central

Goldstein, Robert H; Reagan, Michaela R; Anderson, Kristen; Kaplan, David L; Rosenblatt, Michael

2010-01-01

American women have a nearly 25% lifetime risk of developing breast cancer, with 20–40% of these patients developing life-threatening metastases. Over 70% of patients presenting with metastases have skeletal involvement, which signals progression to an incurable stage. Tumor-stroma cell interactions are only superficially understood, specifically regarding the ability of stromal cells to affect metastasis. In vivo models show that exogenously supplied hBMSCs (human bone-marrow derived stem cells) migrate to breast cancer tumors, but no reports have shown endogenous hBMSC migration from the bone to primary tumors. Here we present a model of in vivo hBMSC migration from a physiologic human bone environment to human breast tumors. Further, hBMSCs alter tumor growth and bone metastasis frequency. hBMSCs may home to certain breast tumors based on tumor-derived TGF-β1. Moreover, at the primary tumor IL-17B/IL-17BR signaling may mediate interactions between hBMSCs and breast cancer cells (BCCs). PMID:21159629

A Novel Temporal Bone Simulation Model Using 3D Printing Techniques.

PubMed

Mowry, Sarah E; Jammal, Hachem; Myer, Charles; Solares, Clementino Arturo; Weinberger, Paul

2015-09-01

An inexpensive temporal bone model for use in a temporal bone dissection laboratory setting can be made using a commercially available, consumer-grade 3D printer. Several models for a simulated temporal bone have been described but use commercial-grade printers and materials to produce these models. The goal of this project was to produce a plastic simulated temporal bone on an inexpensive 3D printer that recreates the visual and haptic experience associated with drilling a human temporal bone. Images from a high-resolution CT of a normal temporal bone were converted into stereolithography files via commercially available software, with image conversion and print settings adjusted to achieve optimal print quality. The temporal bone model was printed using acrylonitrile butadiene styrene (ABS) plastic filament on a MakerBot 2x 3D printer. Simulated temporal bones were drilled by seven expert temporal bone surgeons, assessing the fidelity of the model as compared with a human cadaveric temporal bone. Using a four-point scale, the simulated bones were assessed for haptic experience and recreation of the temporal bone anatomy. The created model was felt to be an accurate representation of a human temporal bone. All raters felt strongly this would be a good training model for junior residents or to simulate difficult surgical anatomy. Material cost for each model was $1.92. A realistic, inexpensive, and easily reproducible temporal bone model can be created on a consumer-grade desktop 3D printer.

Bone formation in vitro and in nude mice by human osteosarcoma cells.

PubMed

Ogose, A; Motoyama, T; Hotta, T; Watanabe, H; Takahashi, H E

1995-01-01

Osteosarcomas contain variable amounts of bony tissue, but the mechanism of bone formation by osteosarcoma is not well understood. While a number of cultured human osteosarcoma cell lines have been established, they are maintained by different media and differ qualitatively with regard to bone formation. We examined different media for their ability to support bone formation in vitro and found the alpha-modification of Eagle's minimal essential medium supplemented with beta glycerophosphate was best for this purpose, because it contained the proper calcium and phosphate concentrations. Subsequently, we compared seven human osteosarcoma cell lines under the same experimental conditions to clarify their ability to induce bone formation. NOS-1 cells most frequently exhibited features of bone formation in vitro and in nude mice. Collagen synthesis by tumour cells themselves seemed to be the most important factor for bone volume. However, even HuO9 cells, which lacked collagen synthesis and failed to form bone in vitro, successfully formed tumours containing bone in nude mice. Histological analysis of HuO9 cells in diffusion chambers implanted in nude mice and the findings of polymerase chain reaction indicated that the phenomenon was probably due to bone morphogenetic protein.

Dietary Strontium Increases Bone Mineral Density in Intact Zebrafish (Danio rerio): A Potential Model System for Bone Research

PubMed Central

Padgett-Vasquez, Steve; Garris, Heath W.; Nagy, Tim R.; D'Abramo, Louis R.; Watts, Stephen A.

2010-01-01

Abstract Zebrafish (Danio rerio) skeletal bone possesses properties similar to human bone, which suggests that they may be used as a model to study mineralization characteristics of the human Haversian system, as well as human bone diseases. One prerequisite for the use of zebrafish as an alternative osteoporotic bone model is to determine whether their bone displays functional plasticity similar to that observed in other bone models. Strontium citrate was supplemented into a laboratory-prepared diet (45% crude protein) to produce dietary strontium levels of 0%, 0.63%, 1.26%, 1.89%, and 2.43% and fed ad libitum twice daily for 12 weeks to 28-day-old intact zebrafish. Length was determined at 4-week intervals, and both weight and length were recorded at 12 weeks. At 12 weeks, seven zebrafish from each dietary level were analyzed for total bone mineral density by microcomputed tomography. Dietary strontium citrate supplementation significantly (p < 0.05) increased zebrafish whole-body and spinal column bone mineral density. In addition, trace amounts of strontium were incorporated into the scale matrix in those zebrafish that consumed strontium-supplemented diets. These findings suggest that zebrafish bone displays plasticity similar to that reported for other bone models (i.e., rat, mouse, and monkey) that received supplements of strontium compounds and zebrafish should be viewed as an increasingly valuable bone model. PMID:20874492

Fabrication method, structure, mechanical, and biological properties of decellularized extracellular matrix for replacement of wide bone tissue defects.

PubMed

Anisimova, N Y; Kiselevsky, M V; Sukhorukova, I V; Shvindina, N V; Shtansky, D V

2015-09-01

The present paper was focused on the development of a new method of decellularized extracellular matrix (DECM) fabrication via a chemical treatment of a native bone tissue. Particular attention was paid to the influence of chemical treatment on the mechanical properties of native bones, sterility, and biological performance in vivo using the syngeneic heterotopic and orthotopic implantation models. The obtained data indicated that after a chemical decellularization treatment in 4% aqueous sodium chlorite, no noticeable signs of the erosion of compact cortical bone surface or destruction of trabeculae of spongy bone in spinal channel were observed. The histological studies showed that the chemical treatment resulted in the decellularization of both bone and cartilage tissues. The DECM samples demonstrated no signs of chemical and biological degradation in vivo. Thorough structural characterization revealed that after decellularization, the mineral frame retained its integrity with the organic phase; however clotting and destruction of organic molecules and fibers were observed. FTIR studies revealed several structural changes associated with the destruction of organic molecules, although all organic components typical of intact bone were preserved. The decellularization-induced structural changes in the collagen constituent resulted changed the deformation under compression mechanism: from the major fracture by crack propagation throughout the sample to the predominantly brittle fracture. Although the mechanical properties of radius bones subjected to decellularization were observed to degrade, the mechanical properties of ulna bones in compression and humerus bones in bending remained unchanged. The compressive strength of both the intact and decellularized ulna bones was 125-130 MPa and the flexural strength of humerus bones was 156 and 145 MPa for the intact and decellularized samples, respectively. These results open new avenues for the use of DECM samples as the replacement of wide bone tissue defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Accumulation of carboxymethyl-lysine (CML) in human cortical bone.

PubMed

Thomas, Corinne J; Cleland, Timothy P; Sroga, Grazyna E; Vashishth, Deepak

2018-05-01

Advanced glycation end-products (AGEs) are a category of post translational modification associated with the degradation of the structural properties of multiple different types of tissues. Typically, AGEs are the result of a series of post-translational modification reactions between sugars and proteins through a process known as non-enzymatic glycation (NEG). Increases in the rate of NEG of bone tissue are associated with type 2 diabetes and skeletal fragility. Current methods of assessing NEG and its impact on bone fracture risk involve measurement of pentosidine or total fluorescent AGEs (fAGEs). However, pentosidine represents only a small fraction of possible fAGEs present in bone, and neither pentosidine nor total fAGE measurement accounts for non-fluorescent AGEs, which are known to form in significant amounts in skin and other collagenous tissues. Carboxymethyl-lysine (CML) is a non-fluorescent AGE that is often measured and has been shown to accumulate in tissues such as skin, heart, arteries, and intervertebral disks, but is currently not assessed in bone. Here we show the localization of CML to collagen I using mass spectrometry for the first time in human bone. We then present a new method using demineralization followed by heating and trypsin digestion to measure CML content in human bone and demonstrate that CML in bone is 40-100 times greater than pentosidine (the current most commonly used marker of AGEs in bone). We then establish the viability of CML as a measurable AGE in bone by showing that levels of CML, obtained from bone using this technique, increase with age (p<0.05) and are correlated with previously reported measures of bone toughness. Thus, CML is a viable non-fluorescent AGE target to assess AGE accumulation and fragility in bone. The method developed here to extract and measure CML from human bone could facilitate the development of a new diagnostic assay to evaluate fracture risk and potentially lead to new therapeutic approaches to address bone fragility. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of naturally occurring and ligature-induced peri-implantitis bone defects in humans and dogs.

PubMed

Schwarz, Frank; Herten, Monika; Sager, Martin; Bieling, Katrin; Sculean, Anton; Becker, Jürgen

2007-04-01

The aim of the present study was to evaluate and compare naturally occuring and ligature-induced peri-implantitis bone defects in humans and dogs. Twenty-four partially and fully edentulous patients undergoing peri-implant bone augmentation procedures due to advanced peri-implant infections were included in this study (n=40 implants). Furthermore, peri-implantitis was induced by ligature placement and plaque accumulation in five beagle dogs for three months following implant insertion (n=15 implants). The ligatures were removed when about 30% of the initial bone was lost. During open flap surgery, configuration and defect characteristics of the peri-implant bone loss were recorded in both humans and dogs. Open flap surgery generally revealed two different classes of peri-implant bone defects. While Class I defects featured well-defined intrabony components, Class II defects were characterized by consistent horizontal bone loss. The allocation of intrabony components of Class I defects regarding the implant body allowed a subdivision of five different configurations (Classes Ia-e). In particular, human defects were most frequently Class Ie (55.3%), followed by Ib (15.8%), Ic (13.3%), Id (10.2%), and Ia (5.4%). Similarly, bone defects in dogs were also most frequently Class Ie (86.6%), while merely two out of 15 defects were Classes Ia and Ic (6.7%, respectively). Within the limits of the present study, it might be concluded that configurations and sizes of ligature-induced peri-implantitis bone defects in dogs seemed to resemble naturally occurring lesions in humans.

The Identification of Proteoglycans and Glycosaminoglycans in Archaeological Human Bones and Teeth

PubMed Central

Coulson-Thomas, Yvette M.; Coulson-Thomas, Vivien J.; Norton, Andrew L.; Gesteira, Tarsis F.; Cavalheiro, Renan P.; Meneghetti, Maria Cecília Z.; Martins, João R.; Dixon, Ronald A.; Nader, Helena B.

2015-01-01

Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeletons. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology. PMID:26107959

[Fluorides in the human bones – selected issues].

PubMed

Palczewska-Komsa, Mirona; Kalisińska, Elżbieta; Stogiera, Anna; Szmidt, Monika

Long -term intake of luoride leads to skeletal luorosis. The toxicity of luoride, not only for the human body, but also the entire ecosystem makes it necessary to constantly monitor their content in the environment. Accordingly, there is a need to control the level of luorides (F⁻) in humans, particularly in bone tissue, which relects long -term accumulation of these compounds. The aim of the study was to determine the concentration of luoride in the human bones depending on biological factors and environmental conditions on the basis of the published literature. Given the importance of bone tissue as the main reservoir of luoride ions is an important issue to continue to monitor the concentration of F⁻ in this tissue, particularly for people living in the polluted environment luorine compounds. There are numerous works on concentrations of this element in human bones in world literature which proves the great interest in the subject. It should be underlined the need for further study of this issue for people living in different regions of Poland.

The use of total human bone marrow fraction in a direct three-dimensional expansion approach for bone tissue engineering applications: focus on angiogenesis and osteogenesis.

PubMed

Guerrero, Julien; Oliveira, Hugo; Catros, Sylvain; Siadous, Robin; Derkaoui, Sidi-Mohammed; Bareille, Reine; Letourneur, Didier; Amédée, Joëlle

2015-03-01

Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.

PubMed

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-09-01

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. © 2014 Anatomical Society.

42 CFR 137.31 - What is included in a compact?

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Self-Governance compact § 137.31 What is... to Indian Tribes and such other terms as the parties intend to control from year to year. ...

42 CFR 137.31 - What is included in a compact?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Self-Governance compact § 137.31 What is... to Indian Tribes and such other terms as the parties intend to control from year to year. ...

75 FR 65028 - Notice of Intent To Repatriate Cultural Items: U.S. Department of Defense, Army Corps of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-21

... shaft smoother, 2 shaft smoother fragments, 1 antler awl fragment, 3 bone awl fragments, 1 bone shaft wrench, 1 bone tube, 17 worked antlers, 10 burned antlers, 1 deer jaw, 19 worked bones, 1 cut bone, 1 burned bone fragment, 1 notched bone, 2 decorated bones, 3 bone strips, 52 miscellaneous non-human bones...

42 CFR 137.49 - What if a Self-Governance Tribe requests such incorporation at the negotiation stage of a compact...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false What if a Self-Governance Tribe requests such incorporation at the negotiation stage of a compact or funding agreement? 137.49 Section 137.49 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL...

[Comparative anatomy of the mandible. Functional aspects].

PubMed

Denoix, J M

1983-12-01

The structural morphology of the mandibula is presented and correlated to various types of mastication in several Mammalian species. The latter include: Carnivores (Dog, Cat, Cheetah, Lion); Omnivores (Man, Chimpanzee, Hog); Herbivores (Horse, Ox, Goat, Camel, Rabbit). While the mandibula is studied as a composite unit, a more analytical, segmental approach has been included, and both are illustrated by X-rays. The aspects presented underline the distribution as well as the local modifications of compact bone, and in addition, the arrangement and the development of spongy bone trabeculae. A preliminary classification with respect to structural elements has been suggested from two viewpoints: that of tension, the other of compression. Are also presented those variations linked to diet and alimentary intake, as well as their functional correlates.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs.

PubMed

Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R

2015-01-01

Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs

PubMed Central

Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R.

2015-01-01

Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older. PMID:26153689

Fabrication of porous calcite using chopped nylon fiber and its evaluation using rats.

PubMed

Ishikawa, Kunio; Tram, Nguyen Xuan Thanh; Tsuru, Kanji; Toita, Riki

2015-02-01

Although porous calcite has attracted attention as bone substitutes, limited studies have been made so far. In the present study, porous calcite block was fabricated by introducing chopped nylon fiber as porogen. Ca(OH)2 powder containing 10 wt% chopped nylon fiber was compacted at 150 MPa, and sintered to burn out the fiber and to carbonate the Ca(OH)2 under stream of 1:2 O2-CO2. Sintering of Ca(OH)2 at 750 °C or lower temperature resulted in incomplete burning out of the fiber whereas sintering at 800 °C or higher temperature resulted in the formation of CaO due to the thermal decomposition of Ca(OH)2. However, sintering at 770 °C resulted in complete burning out of the fiber and complete carbonation of Ca(OH)2 to calcite without forming CaO. Macro- and micro-porosities of the porous calcite were approximately 23 and 16%, respectively. Diameter of the macropores was approximately 100 μm which is suitable for bone tissue penetration. Porous calcite block fabricated by this method exhibited good tissue response when implanted in the bone defect in femur of 12-weeks-old rat. Four weeks after implantation, bone bonded on the surface of calcite. Furthermore, bone tissue penetrated interior to the macropore at 8 weeks. These results demonstrated the good potential value of porous calcite as artificial bone substitutes.

21 CFR 892.1180 - Bone sonometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... device that transmits ultrasound energy into the human body to measure acoustic properties of bone that... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bone sonometer. 892.1180 Section 892.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES...

21 CFR 892.1180 - Bone sonometer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... device that transmits ultrasound energy into the human body to measure acoustic properties of bone that... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Bone sonometer. 892.1180 Section 892.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES...

Immune Humanization of Immunodeficient Mice Using Diagnostic Bone Marrow Aspirates from Carcinoma Patients

PubMed Central

Werner-Klein, Melanie; Proske, Judith; Werno, Christian; Schneider, Katharina; Hofmann, Hans-Stefan; Rack, Brigitte; Buchholz, Stefan; Ganzer, Roman; Blana, Andreas; Seelbach-Göbel, Birgit; Nitsche, Ulrich

2014-01-01

Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses. PMID:24830425

The Nell-1 Growth Factor Stimulates Bone Formation by Purified Human Perivascular Cells

PubMed Central

Zhang, Xinli; Péault, Bruno; Chen, Weiwei; Li, Weiming; Corselli, Mirko; James, Aaron W.; Lee, Min; Siu, Ronald K.; Shen, Pang; Zheng, Zhong; Shen, Jia; Kwak, Jinny; Zara, Janette N.; Chen, Feng; Zhang, Hong; Yin, Zack; Wu, Ben; Ting, Kang

2011-01-01

The search for novel sources of stem cells other than bone marrow mesenchymal stem cells (MSCs) for bone regeneration and repair has been a critical endeavor. We previously established an effective protocol to homogeneously purify human pericytes from multiple fetal and adult tissues, including adipose, bone marrow, skeletal muscle, and pancreas, and identified pericytes as a primitive origin of human MSCs. In the present study, we further characterized the osteogenic potential of purified human pericytes combined with a novel osteoinductive growth factor, Nell-1. Purified pericytes grown on either standard culture ware or human cancellous bone chip (hCBC) scaffolds exhibited robust osteogenic differentiation in vitro. Using a nude mouse muscle pouch model, pericytes formed significant new bone in vivo as compared to scaffold alone (hCBC). Moreover, Nell-1 significantly increased pericyte osteogenic differentiation, both in vitro and in vivo. Interestingly, Nell-1 significantly induced pericyte proliferation and was observed to have pro-angiogenic effects, both in vitro and in vivo. These studies suggest that pericytes are a potential new cell source for future efforts in skeletal regenerative medicine, and that Nell-1 is a candidate growth factor able to induce pericyte osteogenic differentiation. PMID:21615216

Anatomical study of the pigs temporal bone by microdissection.

PubMed

Garcia, Leandro de Borborema; Andrade, José Santos Cruz de; Testa, José Ricardo Gurgel

2014-01-01

Initial study of the pig`s temporal bone anatomy in order to enable a new experimental model in ear surgery. Dissection of five temporal bones of Sus scrofa pigs obtained from UNIFESP - Surgical Skills Laboratory, removed with hole saw to avoid any injury and stored in formaldehyde 10% for better conservation. The microdissection in all five temporal bone had the following steps: inspection of the outer part, external canal and tympanic membrane microscopy, mastoidectomy, removal of external ear canal and tympanic membrane, inspection of ossicular chain and middle ear. Anatomically it is located at the same position than in humans. Some landmarks usually found in humans are missing. The tympanic membrane of the pig showed to be very similar to the human, separating the external and the middle ear. The middle ear`s appearance is very similar than in humans. The ossicular chain is almost exactly the same, as well as the facial nerve, showing the same relationship with the lateral semicircular canal. The temporal bone of the pigs can be used as an alternative for training in ear surgery, especially due the facility to find it and its similarity with temporal bone of the humans.

Microgravity

NASA Image and Video Library

2004-04-15

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc., has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc., is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Microgravity

NASA Image and Video Library

2004-04-15

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc. has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc. is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Recovery of compacted soils in Mojave Desert ghost towns.

USGS Publications Warehouse

Webb, R.H.; Steiger, J.W.; Wilshire, H.G.

1986-01-01

Residual compaction of soils was measured at seven sites in five Mojave Desert ghost towns. Soils in these Death Valley National Monument townsites were compacted by vehicles, animals, and human trampling, and the townsites had been completely abandoned and the buildings removed for 64 to 75 yr. Recovery times extrapolated using a linear recovery model ranged from 80 to 140 yr and averaged 100 yr. The recovery times were related to elevation, suggesting freeze-thaw loosening as an important factor in ameliorating soil compaction in the Mojave Desert. -from Authors

Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases.

PubMed

Ke, Hua Zhu; Richards, William G; Li, Xiaodong; Ominsky, Michael S

2012-10-01

The processes of bone growth, modeling, and remodeling determine the structure, mass, and biomechanical properties of the skeleton. Dysregulated bone resorption or bone formation may lead to metabolic bone diseases. The Wnt pathway plays an important role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of sclerostin leads to substantially increased bone mass in humans and in genetically manipulated animals. Studies in various animal models of bone disease have shown that inhibition of sclerostin using a monoclonal antibody (Scl-Ab) increases bone formation, density, and strength. Additional studies show that Scl-Ab improves bone healing in models of bone repair. Inhibition of DKK1 by monoclonal antibody (DKK1-Ab) stimulates bone formation in younger animals and to a lesser extent in adult animals and enhances fracture healing. Thus, sclerostin and DKK1 are emerging as the leading new targets for anabolic therapies to treat bone diseases such as osteoporosis and for bone repair. Clinical trials are ongoing to evaluate the effects of Scl-Ab and DKK1-Ab in humans for the treatment of bone loss and for bone repair.

[Encounter of cancer cells with bone. Histological examination of bone metastasis].

PubMed

Kanda, Hiroaki

2011-03-01

Management of the cancer bone metastasis is important clinical problem. The mechanism (s) of bone metastasis has been studied mainly by animal models and in vitro system. There might be discrepancy between model systems and in vivo human clinical materials. But there is surprisingly rare study of histological examination of human skeletal metastasis, since it is hard to obtain human materials without modification by chemotherapy or irradiation. There are many surgical materials suitable for this examination in our hospital and we have been examined histological features of them. Stromal cells between metastatic cancer cells and OCs (osteoclasts) and÷or OBs (osteoblasts) might play a role in bone metastasis, since these cells are frequently accompanied with OCs÷OBs. We called these stromal cells as "fibroblast-like cells" and examined their nature and roles in bone metastasis. We hope these fibroblast-like cells might become the target of anti bone metastasis therapy, same as osteoclasts targeted by bisphosphonates.

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulatedmore » with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic acid inhibited RANKL-induced osteoclastogenesis in bone marrow macrophages. • Betulinic acid decreased bone resorption by suppressing osteoclast activity. • Orally administered betulinic acid inhibited cancer-associated bone diseases in mice.« less

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm.

PubMed

Fewtrell, Mary S; Williams, Jane E; Singhal, Atul; Murgatroyd, Peter R; Fuller, Nigel; Lucas, Alan

2009-07-01

Preterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health. To test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data. 20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers. Infant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving >90% human milk had significantly higher WBBA (by 3.5%, p=0.01) and BMC (by 4.8%, p=0.03) than those receiving <10%. Compared to population data, subjects had significantly lower height SDS (-0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (-0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight <1250 g (height SDS -0.81 (0.95), LSBMD SDS -0.61 (1.3)). Infant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.

Upper Palaeolithic ritualistic cannibalism at Gough's Cave (Somerset, UK): The human remains from head to toe.

PubMed

Bello, Silvia M; Saladié, Palmira; Cáceres, Isabel; Rodríguez-Hidalgo, Antonio; Parfitt, Simon A

2015-05-01

A recurring theme of late Upper Palaeolithic Magdalenian human bone assemblages is the remarkable rarity of primary burials and the common occurrence of highly-fragmentary human remains mixed with occupation waste at many sites. One of the most extensive Magdalenian human bone assemblages comes from Gough's Cave, a sizeable limestone cave set in Cheddar Gorge (Somerset), UK. After its discovery in the 1880s, the site was developed as a show cave and largely emptied of sediment, at times with minimal archaeological supervision. Some of the last surviving remnants of sediment within the cave were excavated between 1986 and 1992. The excavations uncovered intensively-processed human bones intermingled with abundant butchered large mammal remains and a diverse range of flint, bone, antler, and ivory artefacts. New ultrafiltrated radiocarbon determinations demonstrate that the Upper Palaeolithic human remains were deposited over a very short period of time, possibly during a series of seasonal occupations, about 14,700 years BP (before present). The human remains have been the subject of several taphonomic studies, culminating in a detailed reanalysis of the cranial remains that showed they had been carefully modified to make skull-cups. Our present analysis of the postcrania has identified a far greater degree of human modification than recorded in earlier studies. We identify extensive evidence for defleshing, disarticulation, chewing, crushing of spongy bone, and the cracking of bones to extract marrow. The presence of human tooth marks on many of the postcranial bones provides incontrovertible evidence for cannibalism. In a wider context, the treatment of the human corpses and the manufacture and use of skull-cups at Gough Cave have parallels with other Magdalenian sites in central and western Europe. This suggests that cannibalism during the Magdalenian was part of a customary mortuary practice that combined intensive processing and consumption of the bodies with ritual use of skull-cups. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

PubMed Central

Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

2014-01-01

Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which resemble the human disease. We have shown the utility of small animal bioimaging for tracking disease progression, making this model a useful assay for preclinical drug testing. PMID:24409320

Influence of Autologus Adipose Derived Stem Cells and PRP on Regeneration of Dehiscence-Type Defects in Alveolar Bone: A Comparative Histochemical and Histomorphometric Study in Dogs

PubMed Central

Aziz Aly, Lobna Abdel; El- Menoufy, Hala; Hassan, Amal; Ragae, Alyaa; Atta, Hazem Mahmoud; Roshdy, Nagwa Kamal; Rashed, Laila Ahmed; Sabry, Dina

2011-01-01

Background and Objectives: Autogenous bone grafts is considered to be the best choice for reconstructive surgery. Adipose Derived Stromal Cells (ASCs) represents a promising tool for new clinical concepts in supporting cellular therapy. The goal of our study was to investigate bone regeneration following application of autologous ASCs with or without Platelet-Rich Plasma (PRP) at dehiscence-type defects in alveolar bone in dogs. Methods and Results: Standardized buccal dehiscence defects (4× 3×3 mm) were surgically created in eighteen dogs, the defects were grafted with either ASCs -PRP, ASCs alone, or without grafting material. Three months later; a bone core was harvested from grafted and non grafted sites for histological, histochemical and histomorphometric assessment. There was no evidence of inflammation or adverse tissue reaction with either treatment. Defects grafted with ASCs-PRP showed a significantly higher result (p≤ 0.05), with a mean area % of spongy bone and compact bone of (64.96±5.37 and 837.62±24.95), compared to ASCs alone (47.65±1.43 and 661.92±12.65) and without grafting (33.55± 1.74 and 290.85±7.27) respectively. The area % of lamellated bone increased significantly reaching its highest level in group A followed by group B. Also a significant increase in area % of neutral mucopolysaccharides and calcified reactivity of Masson|s Trichrome stain in groups A and B compared to group C was obtained. Conclusions: Our results suggest that, the addition of PRP to ASCs enhances bone formation after 3 months and may be clinically effective in accelerating postsurgical healing in both periodontal and maxillofacial surgical applications. PMID:24298335

Three-dimensional structure of human lamellar bone: the presence of two different materials and new insights into the hierarchical organization.

PubMed

Reznikov, Natalie; Shahar, Ron; Weiner, Steve

2014-02-01

Lamellar bone is the most common bone type in humans. The predominant components of individual lamellae are plywood-like arrays of mineralized collagen fibrils aligned in different directions. Using a dual-beam electron microscope and the Serial Surface View (SSV) method we previously identified a small, but significantly different layer in rat lamellar bone, namely a disordered layer with collagen fibrils showing little or no preferred orientation. Here we present a 3D structural analysis of 12 SSV volumes (25 complete lamellae) from femora of 3 differently aged human individuals. We identify the ordered and disordered motifs in human bone as in the rat, with several significant differences. The ordered motif shows two major preferred orientations, perpendicular to the long axis of the bone, and aligned within 10-20° of the long axis, as well as fanning arrays. At a higher organizational level, arrays of ordered collagen fibrils are organized into 'rods' around 2 to 3μm in diameter, and the long axes of these 'rods' are parallel to the lamellar boundaries. Human bone also contains a disordered component that envelopes the rods and fills in the spaces between them. The disordered motif is especially well-defined between adjacent layers of rods. The disordered motif and its interfibrillar substance stain heavily with osmium tetroxide and Alcian blue indicating the presence of another organic component in addition to collagen. The canalicular network is confined to the disordered material, along with voids and individual collagen fibrils, some of which are also aligned more or less perpendicular to the lamellar boundaries. The organization of the ordered fibril arrays into rods enveloped in the continuous disordered structure was not observed in rat lamellar bone. We thus conclude that human lamellar bone is comprised of two distinct materials, an ordered material and a disordered material, and contains an additional hierarchical level of organization composed of arrays of ordered collagen fibrils, referred to as rods. This new structural information on human lamellar bone will improve our understanding of structure-mechanical function relations, mechanisms of mechano-sensing and the characterizations of bone pathologies. Copyright © 2013 Elsevier Inc. All rights reserved.

Bone Factors Regulating the Osteotropism of Metastatic Breast Cancer

DTIC Science & Technology

1998-10-01

growth factors and rapid angiogenesis occurs in the immediate vicinity of an active osteoclast. 4,5 Osteoblast-derived bone sialoprotein (BSP...Cells Antigenic Marker Cells Cultured Alone Cells Co-Cultured (2d) MCF-7 MC3T3 MCF-7 MC3T3 human cytokeratin-+ -1 bone sialoprotein (BSP...proteins. Osteonectin, osteopontin and bone sialoprotein have been studied in a series of human breast cancers. 3,15-3 0 Immunohistochemical evaluation

Non-destructive and non-invasive observation of friction and wear of human joints and of fracture initiation by acoustic emission.

PubMed

Schwalbe, H J; Bamfaste, G; Franke, R P

1999-01-01

Quality control in orthopaedic diagnostics according to DIN EN ISO 9000ff requires methods of non-destructive process control, which do not harm the patient by radiation or by invasive examinations. To obtain an improvement in health economy, quality-controlled and non-destructive measurements have to be introduced into the diagnostics and therapy of human joints and bones. A non-invasive evaluation of the state of wear of human joints and of the cracking tendency of bones is, as of today's point of knowledge, not established. The analysis of acoustic emission signals allows the prediction of bone rupture far below the fracture load. The evaluation of dry and wet bone samples revealed that it is possible to conclude from crack initiation to the bone strength and thus to predict the probability of bone rupture.

Relationships between human cortical bone toughness and collagen cross-links on paired anatomical locations.

PubMed

Gauthier, Rémy; Follet, Hélène; Langer, Max; Gineyts, Evelyne; Rongiéras, Frédéric; Peyrin, Françoise; Mitton, David

2018-07-01

Human cortical bone fracture processes depend on the internal porosity network down to the lacunar length scale. Recent results show that at the collagen scale, the maturation of collagen cross-links may have a negative influence on bone mechanical behavior. While the effect of pentosidine on human cortical bone toughness has been studied, the influence of mature and immature enzymatic cross-links has only been studied in relation to strength and work of fracture. Moreover, these relationships have not been studied on different paired anatomical locations. Thus, the aim of the current study was to assess the relationships between both enzymatic and non-enzymatic collagen cross-links and human cortical bone toughness, on four human paired anatomical locations. Single Edge Notched Bending toughness tests were performed for two loading conditions: a quasi-static standard condition, and a condition representative of a fall. These tests were done with 32 paired femoral diaphyses, femoral necks and radial diaphyses (18 women, age 81 ± 12 y.o.; 14 men, age 79 ± 8 y.o.). Collagen enzymatic and non-enzymatic crosslinks were measured on the same bones. Maturation of collagen was defined as the ratio between immature and mature cross-links (CX). The results show that there was a significant correlation between collagen cross-link maturation and bone toughness when gathering femoral and radial diaphyses, but not when considering each anatomical location individually. These results show that the influence of collagen enzymatic and non-enzymatic cross-links is minor when considering human cortical bone crack propagation mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

The Hopper: A Wearable Robotic Device Testbed for Micro-Gravity Bone-Loading Proof-of-Concept

NASA Technical Reports Server (NTRS)

Beck, C. E.; Rovekamp, R. N.; Neuhaus, P. D.

2015-01-01

Wearable robotic systems are showing increased potential for addressing crew countermeasures needs. Wearable robots offer a compactness, programmability, and eccentric loading capability not present in more conventional exercise equipment. Correspondingly, advancements in the man to machine interface has progressed, allowing for higher loads to be applied directly to the person in new and novel ways. Recently, the X1 exoskeleton, a lower extremity wearable robot originally designed for mobility assistance and rehabilitation, underwent human subject testing to assess its potential as a knee dynamometer. This was of interest to NASA physiologists because currently strength is not assessed in flight due to hardware limitations, and thus there is a poor understanding of the time course of in-flight changes to muscle strength. The study concluded that the X1 compared well with the Biodex, the "gold standard" in terrestrial dynamometry, with coefficients of variation less than 6.0%. In a following study, the X1 powered ankle was evaluated for its efficacy in exercising calf muscles. Current on-orbit countermeasures equipment does not adequately protect the calf from atrophy. The results of this study were also positive (targeted muscle activity demonstrated via comparing pre- and post-exercise magnetic resonance imaging T2 measurements), again showing the efficacy of wearable robotic devices for addressing the countermeasure needs of our astronauts. Based on these successes and lessons learned, the Grasshopper was co-developed between IHMC (Florida Institute for Human and Machine Cognition) and NASA. The Grasshopper, or the Hopper for short, is a wearable robotic device designed to address muscle and bone density loss for astronauts spending extended periods of time in micro-gravity. The Grasshopper connects to the user's torso like a hiking backpack, over the shoulders and around the waist. At the feet are footplates that strap to the user. There are two actuators, one at each "knee" joint, which are capable of high fidelity torque control. Because the Hopper uses motors instead of gravity to create the load on the user, the device is suited for use on space missions. Exercise in zero-gravity conditions is critical to maintain muscle strength and bone mass. In operation, the actuators try to fold up, or collapse, the device, putting a compressive load between the user's feet and torso. This force is similar to carrying a heavy backpack. The user then bends and extends his or her knees, replicating a weightlifting squat exercise. The applied load is precisely controlled by a computer, and can be programmed to simulate gravitation loads or any desired load prescription, such as free-weight squat exercise. It is even possible to perform eccentric exercises, or negatives, without the need for a spotter. Because the hip joints, as well as the spine and long leg bones, are in the applied load path, there is the potential to stimulate bone growth, countering the typical bone loss when astronauts return from extended duration space travel.

Micro-CT characterization of human trabecular bone in osteogenesis imperfecta

NASA Astrophysics Data System (ADS)

Jameson, John; Albert, Carolyne; Smith, Peter; Molthen, Robert; Harris, Gerald

2011-03-01

Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment.

[Significance of bone mineral density and modern cementing technique for in vitro cement penetration in total shoulder arthroplasty].

PubMed

Pape, G; Raiss, P; Kleinschmidt, K; Schuld, C; Mohr, G; Loew, M; Rickert, M

2010-12-01

Loosening of the glenoid component is one of the major causes of failure in total shoulder arthroplasty. Possible risk factors for loosening of cemented components include an eccentric loading, poor bone quality, inadequate cementing technique and insufficient cement penetration. The application of a modern cementing technique has become an established procedure in total hip arthroplasty. The goal of modern cementing techniques in general is to improve the cement-penetration into the cancellous bone. Modern cementing techniques include the cement vacuum-mixing technique, retrograde filling of the cement under pressurisation and the use of a pulsatile lavage system. The main purpose of this study was to analyse cement penetration into the glenoid bone by using modern cement techniques and to investigate the relationship between the bone mineral density (BMD) and the cement penetration. Furthermore we measured the temperature at the glenoid surface before and after jet-lavage of different patients during total shoulder arthroplasty. It is known that the surrounding temperature of the bone has an effect on the polymerisation of the cement. Data from this experiment provide the temperature setting for the in-vitro study. The glenoid surface temperature was measured in 10 patients with a hand-held non-contact temperature measurement device. The bone mineral density was measured by DEXA. Eight paired cadaver scapulae were allocated (n = 16). Each pair comprised two scapulae from one donor (matched-pair design). Two different glenoid components were used, one with pegs and the other with a keel. The glenoids for the in-vitro study were prepared with the bone compaction technique by the same surgeon in all cases. Pulsatile lavage was used to clean the glenoid of blood and bone fragments. Low viscosity bone cement was applied retrogradely into the glenoid by using a syringe. A constant pressure was applied with a modified force sensor impactor. Micro-computed tomography scans were applied to analyse the cement penetration into the cancellous bone. The mean temperature during the in-vivo arthroplasty of the glenoid was 29.4 °C (27.2-31 °C) before and 26.2 °C (25-27.5 °C) after jet-lavage. The overall peak BMD was 0.59 (range 0.33-0.99) g/cm (2). Mean cement penetration was 107.9 (range 67.6-142.3) mm (2) in the peg group and 128.3 (range 102.6-170.8) mm (2) in the keel group. The thickness of the cement layer varied from 0 to 2.1 mm in the pegged group and from 0 to 2.4 mm in the keeled group. A strong negative correlation between BMD and mean cement penetration was found for the peg group (r (2) = -0.834; p < 0.01) and for the keel group (r (2) = -0.727; p < 0.041). Micro-CT shows an inhomogenous dispersion of the cement into the cancellous bone. Data from the in-vivo temperature measurement indicate that the temperature at the glenohumeral surface under operation differs from the body core temperature and should be considered in further in-vitro studies with human specimens. Bone mineral density is negatively correlated to cement penetration in the glenoid. The application of a modern cementing technique in the glenoid provides sufficient cementing penetration although there is an inhomogenous dispersion of the cement. The findings of this study should be considered in further discussions about cementing technique and cement penetration into the cancellous bone of the glenoid. © Georg Thieme Verlag KG Stuttgart · New York.

42 CFR 137.96 - Does the Prompt Payment Act apply to funds transferred to a Self-Governance Tribe in a compact or...

Code of Federal Regulations, 2010 CFR

2010-10-01

... transferred to a Self-Governance Tribe in a compact or funding agreement? 137.96 Section 137.96 Public Health... HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Funding Prompt Payment Act § 137.96 Does the Prompt Payment Act apply to funds transferred to a Self-Governance Tribe in a compact or funding agreement? Yes...

T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.

PubMed

Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F

2016-09-01

TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.

Variations in Urine Calcium Isotope: Composition Reflect Changes in Bone Mineral Balance in Humans

NASA Technical Reports Server (NTRS)

Skulan, Joseph; Anbar, Ariel; Bullen, Thomas; Puzas, J. Edward; Shackelford, Linda; Smith, Scott M.

2004-01-01

Changes in bone mineral balance cause rapid and systematic changes in the calcium isotope composition of human urine. Urine from subjects in a 17 week bed rest study was analyzed for calcium isotopic composition. Comparison of isotopic data with measurements of bone mineral density and metabolic markers of bone metabolism indicates the calcium isotope composition of urine reflects changes in bone mineral balance. Urine calcium isotope composition probably is affected by both bone metabolism and renal processes. Calcium isotope. analysis of urine and other tissues may provide information on bone mineral balance that is in important respects better than that available from other techniques, and illustrates the usefulness of applying geochemical techniques to biomedical problems.

Reduced bone density in androgen-deficient women with acquired immune deficiency syndrome wasting.

PubMed

Huang, J S; Wilkie, S J; Sullivan, M P; Grinspoon, S

2001-08-01

Women with acquired immune deficiency syndrome wasting are at an increased risk of osteopenia because of low weight, changes in body composition, and hormonal alterations. Although women comprise an increasing proportion of human immunodeficiency virus-infected patients, prior studies have not investigated bone loss in this expanding population of patients. In this study we investigated bone density, bone turnover, and hormonal parameters in 28 women with acquired immune deficiency syndrome wasting and relative androgen deficiency (defined as free testosterone < or =3.0 pg/ml, weight < or =90% ideal body weight, weight loss > or =10% from preillness maximum weight, or weight <100% ideal body weight with weight loss > or =5% from preillness maximum weight). Total body (1.04 +/- 0.08 vs. 1.10 +/- 0.07 g/cm2, human immunodeficiency virus-infected vs. control respectively; P < 0.01), anteroposterior lumbar spine (0.94 +/- 0.12 vs. 1.03 +/- 0.09 g/cm2; P = 0.005), lateral lumbar spine (0.71 +/- 0.14 vs. 0.79 +/- 0.09 g/cm2; P = 0.02), and hip (Ward's triangle; 0.68 +/- 0.14 vs. 0.76 +/- 0.12 g/cm2; P = 0.05) bone density were reduced in the human immunodeficiency virus-infected compared with control subjects. Serum N-telopeptide, a measure of bone resorption, was increased in human immunodeficiency virus-infected patients, compared with control subjects (14.6 +/- 5.8 vs. 11.3 +/- 3.8 nmol/liter bone collagen equivalents, human immunodeficiency virus-infected vs. control respectively; P = 0.03). Although body mass index was similar between the groups, muscle mass was significantly reduced in the human immunodeficiency virus-infected vs. control subjects (16 +/- 4 vs. 21 +/- 4 kg, human immunodeficiency virus-infected vs. control, respectively; P < 0.0001). In univariate regression analysis, muscle mass (r = 0.53; P = 0.004) and estrogen (r = 0.51; P = 0.008), but not free testosterone (r = -0.05, P = 0.81), were strongly associated with lumbar spine bone density in the human immunodeficiency virus-infected patients. The association between muscle mass and bone density remained significant, controlling for body mass index, hormonal status, and age (P = 0.048) in multivariate regression analysis. These data indicate that both hormonal and body composition factors contribute to reduced bone density in women with acquired immune deficiency syndrome wasting. Anabolic strategies to increase muscle mass may be useful to increase bone density among osteopenic women with acquired immune deficiency syndrome wasting.

A comparison of fatigue crack growth in human enamel and hydroxyapatite.

PubMed

Bajaj, Devendra; Nazari, Ahmad; Eidelman, Naomi; Arola, Dwayne D

2008-12-01

Cracks and craze lines are often observed in the enamel of human teeth, but they rarely cause tooth fracture. The present study evaluates fatigue crack growth in human enamel, and compares that to the fatigue response of sintered hydroxyapatite (HAp) with similar crystallinity, chemistry and density. Miniature inset compact tension (CT) specimens were prepared that embodied a small piece of enamel (N=8) or HAp (N=6). The specimens were subjected to mode I cyclic loads and the steady state crack growth responses were modeled using the Paris Law. Results showed that the fatigue crack growth exponent (m) for enamel (m=7.7+/-1.0) was similar to that for HAp (m=7.9+/-1.4), whereas the crack growth coefficient (C) for enamel (C=8.7 E-04 (mm/cycle)x(MPa m(0.5))(-m)) was significantly lower (p<0.0001) than that for HAp (C=2.0 E+00 (mm/cycle)x(MPa m(0.5))(-m)). Micrographs of the fracture surfaces showed that crack growth in the enamel occurred primarily along the prism boundaries. In regions of decussation, the microstructure promoted microcracking, crack bridging, crack deflection and crack bifurcation. Working in concert, these mechanisms increased the crack growth resistance and resulted in a sensitivity to crack growth (m) similar to bone and lower than that of human dentin. These mechanisms of toughening were not observed in the crack growth response of the sintered HAp. While enamel is the most highly mineralized tissue of the human body, the microstructural arrangement of the prisms promotes exceptional resistance to crack growth.

A Comparison of Fatigue Crack Growth in Human Enamel and Hydroxyapatite

PubMed Central

Bajaj, Devendra; Nazari, Ahmad; Eidelman, Naomi; Arola, Dwayne

2008-01-01

Cracks and craze lines are often observed in the enamel of human teeth, but they rarely cause tooth fracture. The present study evaluates fatigue crack growth in human enamel, and compares that to the fatigue response of sintered hydroxyapatite (HAp) with similar crystallinity, chemistry and density. Miniature inset compact tension (CT) specimens were prepared that embodied a small piece of enamel (N=8) or HAp (N=6). The specimens were subjected to mode I cyclic loads and the steady state crack growth responses were modeled using the Paris Law. Results showed that the fatigue crack growth exponent (m) for enamel (m = 7.7±1.0) was similar to that for HAp (m = 7.9±1.4), whereas the crack growth coefficient (C) for enamel (C=8.7E-04 (mm/cycle)·(MPa·m0.5)-m) was significantly lower (p<0.0001) than that for HAp (C = 2.0E+00 (mm/cycle)·(MPa·m0.5)-m). Micrographs of the fracture surfaces showed that crack growth in the enamel occurred primarily along the prism boundaries. In regions of decussation, the microstructure promoted microcracking, crack bridging, crack deflection and crack bifurcation. Working in concert, these mechanisms increased the crack growth resistance and resulted in a sensitivity to crack growth (m) similar to bone and lower than that of human dentin. These mechanisms of toughening were not observed in the crack growth response of the sintered HAp. While enamel is the most highly mineralized tissue of the human body, the microstructural arrangement of the prisms promotes exceptional resistance to crack growth. PMID:18804277

Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts.

PubMed

Amiable, Nathalie; Tat, Steeve Kwan; Lajeunesse, Daniel; Duval, Nicolas; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Boileau, Christelle

2009-06-01

In osteoarthritis (OA), the subchondral bone undergoes a remodelling process involving several factors synthesized by osteoblasts. In this study, we investigated the expression, production, modulation, and role of PAR-2 in human OA subchondral bone osteoblasts. PAR-2 expression and production were determined by real-time PCR and flow cytometry, respectively. PAR-2 modulation was investigated in OA subchondral bone osteoblasts treated with IL-1 beta (100 pg/ml), TNF-alpha (5 ng/ml), TGF-beta1 (10 ng/ml), PGE(2) (500 nM), IL-6 (10 ng/ml) and IL-17 (10 ng/ml). Membranous RANKL protein was assessed by flow cytometry, and OPG, MMP-1, MMP-9, MMP-13, IL-6 and intracellular signalling pathways by specific ELISAs. Bone resorptive activity was measured by using a co-culture model of human PBMC and OA subchondral bone osteoblasts. PAR-2 expression and production (p<0.05) were markedly increased when human OA subchondral bone osteoblasts were compared to normal. On OA osteoblasts, PAR-2 production was significantly increased by IL-1 beta, TNF-alpha and PGE(2). Activation of PAR-2 with a specific agonist, SLIGKV-NH(2), induced a significant up-regulation of MMP-1, MMP-9, IL-6, and membranous RANKL, but had no effect on MMP-13 or OPG production. Interestingly, bone resorptive activity was also significantly enhanced following PAR-2 activation. The PAR-2 effect was mediated by activation of the MAP kinases Erk1/2 and JNK. This study is the first to demonstrate that PAR-2 activation plays a role in OA subchondral bone resorption via an up-regulation of major bone remodelling factors. These results shed new light on the potential of PAR-2 as a therapeutic target in OA.

Tendon Healing in Bone Tunnel after Human Anterior Cruciate Ligament Reconstruction: A Systematic Review of Histological Results.

PubMed

Lu, Hongbin; Chen, Can; Xie, Shanshan; Tang, Yifu; Qu, Jin

2018-05-21

Most studies concerning to tendon healing and incorporation into bone are mainly based on animal studies due to the invasive nature of the biopsy procedure. The evidence considering tendon graft healing to bone in humans is limited in several case series or case reports, and therefore, it is difficult to understand the healing process. A computerized search using relevant search terms was performed in the PubMed, EMBASE, Scopus, and Cochrane Library databases, as well as a manual search of reference lists. Searches were limited to studies that investigated tendon graft healing to bone by histologic examination after anterior cruciate ligament (ACL) reconstruction with hamstring. Ten studies were determined to be eligible for this systematic review. Thirty-seven cases were extracted from the included studies. Most studies showed that a fibrovascular interface would form at the tendon-bone interface at the early stage and a fibrous indirect interface with Sharpey-like fibers would be expected at the later stage. Cartilage-like tissue at tendon graft-bone interface was reported in three studies. Tendon graft failed to integrate with the surrounding bone in 10 of the 37 cases. Unexpectedly, suspensory type of fixation was used for the above failure cases. An indirect type of insertion with Sharpey-like fibers at tendon-bone interface could be expected after ACL reconstruction with hamstring. Regional cartilage-like tissue may form at tendon-bone interface occasionally. The underlying tendon-to-bone healing process is far from understood in the human hamstring ACL reconstruction. Further human studies are highly needed to understand tendon graft healing in bone tunnel after hamstring ACL reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

PubMed Central

Tsutsumimoto, Takahiro; Williams, Paul; Yoneda, Toshiyuki

2014-01-01

Neuroblastoma (NB), which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2). In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB. PMID:26909300

QUANTITATIVE PLUTONIUM MICRODISTRIBUTION IN BONE TISSUE OF VERTEBRA FROM A MAYAK WORKER

PubMed Central

Lyovkina, Yekaterina V.; Miller, Scott C.; Romanov, Sergey A.; Krahenbuhl, Melinda P.; Belosokhov, Maxim V.

2010-01-01

The purpose was to obtain quantitative data on plutonium microdistribution in different structural elements of human bone tissue for local dose assessment and dosimetric models validation. A sample of the thoracic vertebra was obtained from a former Mayak worker with a rather high plutonium burden. Additional information was obtained on occupational and exposure history, medical history, and measured plutonium content in organs. Plutonium was detected in bone sections from its fission tracks in polycarbonate film using neutron-induced autoradiography. Quantitative analysis of randomly selected microscopic fields on one of the autoradiographs was performed. Data included fission fragment tracks in different bone tissue and surface areas. Quantitative information on plutonium microdistribution in human bone tissue was obtained for the first time. From these data, quantitative relationship of plutonium decays in bone volume to decays on bone surface in cortical and trabecular fractions were defined as 2.0 and 0.4, correspondingly. The measured quantitative relationship of decays in bone volume to decays on bone surface does not coincide with recommended models for the cortical bone fraction by the International Commission on Radiological Protection. Biokinetic model parameters of extrapulmonary compartments might need to be adjusted after expansion of the data set on quantitative plutonium microdistribution in other bone types in human as well as other cases with different exposure patterns and types of plutonium. PMID:20838087

Restoration of a Critical Mandibular Bone Defect Using Human Alveolar Bone-Derived Stem Cells and Porous Nano-HA/Collagen/PLA Scaffold

PubMed Central

Wang, Xing; Xing, Helin; Zhang, Guilan; Wu, Xia; Zou, Xuan; Feng, Lin; Wang, Dongsheng; Li, Meng; Zhao, Jing; Du, Jianwei; Lv, Yan; E, Lingling; Liu, Hongchen

2016-01-01

Periodontal bone defects occur in a wide variety of clinical situations. Adult stem cell- and biomaterial-based bone tissue regeneration are a promising alternative to natural bone grafts. Recent evidence has demonstrated that two populations of adult bone marrow mesenchymal stromal cells (BMSCs) can be distinguished based on their embryonic origins. These BMSCs are not interchangeable, as bones preferentially heal using cells that share the same embryonic origin. However, the feasibility of tissue engineering using human craniofacial BMSCs was unclear. The goal of this study was to explore human craniofacial BMSC-based therapy for the treatment of localized mandibular defects using a standardized, minimally invasive procedure. The BMSCs' identity was confirmed. Scanning electron microscopy, a cell proliferation assay, and supernatant detection indicated that the nHAC/PLA provided a suitable environment for aBMSCs. Real-time PCR and electrochemiluminescence immunoassays demonstrated that osteogenic markers were upregulated by osteogenic preinduction. Moreover, in a rabbit critical-size mandibular bone defect model, total bone formation in the nHAC/PLA + aBMSCs group was significantly higher than in the nHAC/PLA group but significantly lower than in the nHAC/PLA + preinduced aBMSCs. These findings demonstrate that this engineered bone is a valid alternative for the correction of mandibular bone defects. PMID:27118977

Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms.

PubMed

Li, Zhi Gang; Mathew, Paul; Yang, Jun; Starbuck, Michael W; Zurita, Amado J; Liu, Jie; Sikes, Charles; Multani, Asha S; Efstathiou, Eleni; Lopez, Adriana; Wang, Jing; Fanning, Tina V; Prieto, Victor G; Kundra, Vikas; Vazquez, Elba S; Troncoso, Patricia; Raymond, Austin K; Logothetis, Christopher J; Lin, Sue-Hwa; Maity, Sankar; Navone, Nora M

2008-08-01

In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.

Androgen receptor–negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms

PubMed Central

Li, Zhi Gang; Mathew, Paul; Yang, Jun; Starbuck, Michael W.; Zurita, Amado J.; Liu, Jie; Sikes, Charles; Multani, Asha S.; Efstathiou, Eleni; Lopez, Adriana; Wang, Jing; Fanning, Tina V.; Prieto, Victor G.; Kundra, Vikas; Vazquez, Elba S.; Troncoso, Patricia; Raymond, Austin K.; Logothetis, Christopher J.; Lin, Sue-Hwa; Maity, Sankar; Navone, Nora M.

2008-01-01

In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor–negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer–induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor–null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells. PMID:18618013

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis.

PubMed

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D; Davies, John E; Stanford, William L

2016-05-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance--replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. ©AlphaMed Press.

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis

PubMed Central

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D.

2016-01-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance—replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. Significance This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. PMID:26987353

Development of a strain rate dependent material model of human cortical bone for computer-aided reconstruction of injury mechanisms.

PubMed

Asgharpour, Zahra; Zioupos, Peter; Graw, Matthias; Peldschus, Steffen

2014-03-01

Computer-aided methods such as finite-element simulation offer a great potential in the forensic reconstruction of injury mechanisms. Numerous studies have been performed on understanding and analysing the mechanical properties of bone and the mechanism of its fracture. Determination of the mechanical properties of bones is made on the same basis used for other structural materials. The mechanical behaviour of bones is affected by the mechanical properties of the bone material, the geometry, the loading direction and mode and of course the loading rate. Strain rate dependency of mechanical properties of cortical bone has been well demonstrated in literature studies, but as many of these were performed on animal bones and at non-physiological strain rates it is questionable how these will apply in the human situations. High strain-rates dominate in a lot of forensic applications in automotive crashes and assault scenarios. There is an overwhelming need to a model which can describe the complex behaviour of bone at lower strain rates as well as higher ones. Some attempts have been made to model the viscoelastic and viscoplastic properties of the bone at high strain rates using constitutive mathematical models with little demonstrated success. The main objective of the present study is to model the rate dependent behaviour of the bones based on experimental data. An isotropic material model of human cortical bone with strain rate dependency effects is implemented using the LS-DYNA material library. We employed a human finite element model called THUMS (Total Human Model for Safety), developed by Toyota R&D Labs and the Wayne State University, USA. The finite element model of the human femur is extracted from the THUMS model. Different methods have been employed to develop a strain rate dependent material model for the femur bone. Results of one the recent experimental studies on human femur have been employed to obtain the numerical model for cortical femur. A forensic application of the model is explained in which impacts to the arm have been reconstructed using the finite element model of THUMS. The advantage of the numerical method is that a wide range of impact conditions can be easily reconstructed. Impact velocity has been changed as a parameter to find the tolerance levels of injuries to the lower arm. The method can be further developed to study the assaults and the injury mechanism which can lead to severe traumatic injuries in forensic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mammalian bone palaeohistology: a survey and new data with emphasis on island forms

PubMed Central

Scheyer, Torsten M.; Veitschegger, Kristof; Forasiepi, Analia M.; Amson, Eli; Van der Geer, Alexandra A.E.; Van den Hoek Ostende, Lars W.; Hayashi, Shoji; Sánchez-Villagra, Marcelo R.

2015-01-01

The interest in mammalian palaeohistology has increased dramatically in the last two decades. Starting in 1849 via descriptive approaches, it has been demonstrated that bone tissue and vascularisation types correlate with several biological variables such as ontogenetic stage, growth rate, and ecology. Mammalian bone displays a large variety of bone tissues and vascularisation patterns reaching from lamellar or parallel-fibred to fibrolamellar or woven-fibred bone, depending on taxon and individual age. Here we systematically review the knowledge and methods on cynodont and mammalian bone microstructure as well as palaeohistology and discuss potential future research fields and techniques. We present new data on the bone microstructure of two extant marsupial species and of several extinct continental and island placental mammals. Extant marsupials display mainly parallel-fibred primary bone with radial and oblique but mainly longitudinal vascular canals. Three juvenile specimens of the dwarf island hippopotamid Hippopotamus minor from the Late Pleistocene of Cyprus show reticular to plexiform fibrolamellar bone. The island murid Mikrotia magna from the Late Miocene of Gargano, Italy displays parallel-fibred primary bone with reticular vascularisation and strong remodelling in the middle part of the cortex. Leithia sp., the dormouse from the Pleistocene of Sicily, is characterised by a primary bone cortex consisting of lamellar bone and a high amount of compact coarse cancellous bone. The bone cortex of the fossil continental lagomorph Prolagus oeningensis and three fossil species of insular Prolagus displays mainly parallel-fibred primary bone and reticular, radial as well as longitudinal vascularisation. Typical for large mammals, secondary bone in the giant rhinocerotoid Paraceratherium sp. from the Late Oligocene of Turkey is represented by dense Haversian bone. The skeletochronological features of Sinomegaceros yabei, a large-sized deer from the Pleistocene of Japan closely related to Megaloceros, indicate a high growth rate. These examples and the synthesis of existing data show the potential of bone microstructure to reveal essential information on life history evolution. The bone tissue and the skeletochronological data of the sampled island species suggest the presence of various modes of bone histological modification and mammalian life history evolution on islands to depend on factors of island evolution such as island size, distance from mainland, climate, phylogeny, and time of evolution. PMID:26528418

The impact of microgravity on bone in humans.

PubMed

Grimm, Daniela; Grosse, Jirka; Wehland, Markus; Mann, Vivek; Reseland, Janne Elin; Sundaresan, Alamelu; Corydon, Thomas Juhl

2016-06-01

Experiencing real weightlessness in space is a dream for many of us who are interested in space research. Although space traveling fascinates us, it can cause both short-term and long-term health problems. Microgravity is the most important influence on the human organism in space. The human body undergoes dramatic changes during a long-term spaceflight. In this review, we will mainly focus on changes in calcium, sodium and bone metabolism of space travelers. Moreover, we report on the current knowledge on the mechanisms of bone loss in space, available models to simulate the effects of microgravity on bone on Earth as well as the combined effects of microgravity and cosmic radiation on bone. The available countermeasures applied in space will also be evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

PubMed

Prisby, Rhonda D

2014-07-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone Marrow Blood Vessel Ossification and “Microvascular Dead Space” in Rat and Human Long Bone

PubMed Central

Prisby, Rhonda D.

2014-01-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6 mon; n=8) and old (22–24 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner’s Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via µCT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p <0.05) in old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p <0.05) 262%, 375% and 263%, respectively, in old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in “microvascular dead space” in regards to loss of patency and vasomotor function as opposed to necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. PMID:24680721

Surface modifications of the Sima de los Huesos fossil humans.

PubMed

Andrews, P; Fernandez Jalvo, Y

1997-01-01

The sample of fossil human bones from the Sima de los Huesos, Atapuerca, has been analysed to trace parts of its taphonomic history. The work reported here is restricted to analysis of the skeletal elements preserved and their surface modifications. Preliminary plans of specimen distribution published 6 years ago indicate that the skeletal elements are dispersed within the cave, but more recent data are not yet available. Most of the fossils are broken, with some breakage when the bone was fresh and some when already partly mineralized, both types showing some rounding. There are few longitudinal breaks on shafts of long bones and so very few bone splinters. All skeletal elements are preserved but in unequal proportions, with elements like femora, humeri and mandibles and teeth with greater structural density being best represented. There is no evidence of weathering or of human damage such as cut marks on any of the human assemblage, but trampling damage is present on most bones. Carnivore damage is also common, with some present on more than half the sample, but it is mostly superficial, either on the surfaces of shafts and articular ends or on the edges of spiral breaks. The sizes and distribution of the carnivore pits indicate extensive canid activity, and this is interpreted as scavenging of the bones in place in the cave. Indications of tooth marks from a larger carnivore indicate the activity possibly of a large felid: the marks are too large to be produced by small canids, with the larger marks concentrated on spiral breaks on the more robust bones, and there is no evidence of bone crushing and splintering in the manner of hyaenas. The nature of the SH human assemblage is also consistent with accumulation by humans, the evidence for this being the lack of other animals, especially the lack of herbivorous animals, associated with the humans, and the high number of individuals preserved.

A new anthropometric phantom for calibrating in vivo measurements of stable lead in the human leg using X-ray fluorescence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spitz, H.; Jenkins, M.; Lodwick, J.

2000-02-01

A new anthropometric phantom has been developed for calibrating in vivo measurements of stable lead deposited in bone using x-ray fluorescence. The phantom reproduces the shape of the mid shaft of the adult human leg and is fabricated using polyurethanes and calcium carbonate to produce materials that exhibit the same density, energy transmission, and calcium content as cortical bone, bone marrow, and muscle. The phantom includes a removable tibia fabricated using simulants for cortical bone and bone marrow to which a precise amount of stable lead has been added to cortical bone. The formulations used in fabricating the new anthropometricmore » phantom are much more uniform in density and composition than the conventional phantom made from Plexiglas cylinders filled with plaster-of-Paris. The energy spectrum from an x-ray fluorescence measurement of the phantom using a {sup 109}Cd source is indistinguishable from an in vivo x-ray fluorescence measurement of the human leg, demonstrating that the materials used in the phantom exhibit the same radiological properties as human tissue. Likewise, results from x-ray fluorescence measurements of the phantom exhibit the same positional dependency as the human leg and vary by approximately 36% when, for example, the phantom containing 54 ppm of stable lead in the tibia was rotated by only 15 degrees. The detection limit for a 30 min {sup 109}Cd K shell x-ray fluorescence in vivo measurement is approximately 20 ppm determined from a background measurement using the new phantom containing no added lead in the muscle, bone, or bone marrow. The new anthropometric phantom significantly improves in vivo x-ray fluorescence calibration measurements by (1) faithfully reproducing the anatomy of the human leg, (2) having components that exhibit radiological properties similar to that of human tissue, and (3) providing a realistic calibration standard that can be used for in vivo x-ray fluorescence intercomparison measurements.« less

Fantastic plastic? Experimental evaluation of polyurethane bone substitutes as proxies for human bone in trauma simulations.

PubMed

Smith, Martin J; James, Stephen; Pover, Tim; Ball, Nina; Barnetson, Victoria; Foster, Bethany; Guy, Carl; Rickman, John; Walton, Virginia

2015-09-01

Recent years have seen steady improvements in the recognition and interpretation of violence related injuries in human skeletal remains. Such work has at times benefited from the involvement of biological anthropologists in forensic casework and has often relied upon comparison of documented examples with trauma observed in skeletal remains. In cases where no such example exists investigators must turn to experimentation. The selection of experimental samples is problematic as animal proxies may be too dissimilar to humans and human cadavers may be undesirable for a raft of reasons. The current article examines a third alternative in the form of polyurethane plates and spheres marketed as viable proxies for human bone in ballistic experiments. Through subjecting these samples to a range of impacts from both modern and archaic missile weapons it was established that such material generally responds similarly to bone on a broad, macroscopic scale but when examined in closer detail exhibits a range of dissimilarities that call for caution in extrapolating such results to real bone. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Progesterone Promotes Human Bone Marrow Mesenchymal Stem Cells to Synthesize Fibronectin via ERK Pathway].

PubMed

Wu, Zhen-Yong; Chen, Jing-Li; Huang, Shu; Zhang, Hui; Wang, Fang; Wang, Yan; Bi, Xiao-Yun; Guo, Zi-Kuan

2015-12-01

To investigate whether the progesterone can promote fibronection (FN) synthesis by human bone marrow mesenchymal stem cells (MSCs) and to explore the potential underlying mechanism. The human bone marrow MSCs were cultured in a serum-free medium with progesterone for 72 hours, the MTT test was performed to observe the proliferation status and adhension ability of the treated cells. Western blot was used to detect the content of FN in MSDs with GAPDH as the internal reference, the phosphorylation of ERK1/2, as well as the FN content in MSC treated by PD98059, a specific inhibitor of ERK1/2. The progesterone at a range of certain doses not effect on the proliferation of human bone marrow MSCs. Progesterone (25 µg/L) treatment enhanced the FN expression and adherent ability of marrow MSCs. Progesterone could induce prompt phosphorylation of ERK 1/2 and its promoting effects on FN synthesis was reversed by PD98059. The progesterone can promote FN synthesis by human bone marrow MSCs via ERK 1/2 pathway, and it might be used to culture MSCs in serum-free medium.

Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging.

PubMed

Jeffery, Justin J; Lux, Katie; Vogel, John S; Herrera, Wynetta D; Greco, Stephen; Woo, Ho-Hyung; AbuShahin, Nisreen; Pagel, Mark D; Chambers, Setsuko K

2014-04-01

Breast cancer cells preferentially home to the bone microenvironment, which provides a unique niche with a network of multiple bidirectional communications between host and tumor, promoting survival and growth of bone metastases. In the bone microenvironment, the c-fms proto-oncogene that encodes for the CSF-1 receptor, along with CSF-1, serves as one critical cytokine/receptor pair, functioning in paracrine and autocrine fashion. Previous studies concentrated on the effect of inhibition of host (mouse) c-fms on bone metastasis, with resulting decrease in osteolysis and bone metastases as a paracrine effect. In this report, we assessed the role of c-fms inhibition within the tumor cells (autocrine effect) in the early establishment of breast cancer cells in bone and the effects of this early c-fms inhibition on subsequent bone metastases and destruction. This study exploited a multidisciplinary approach by employing two non-invasive, in vivo imaging methods to assess the progression of bone metastases and bone destruction, in addition to ex vivo analyses using RT-PCR and histopathology. Using a mouse model of bone homing human breast cancer cells, we showed that an early one-time application of anti-human c-fms antibody delayed growth of bone metastases and bone destruction for at least 31 days as quantitatively measured by bioluminescence imaging and computed tomography, compared to controls. Thus, neutralizing human c-fms in the breast cancer cell alone decreases extent of subsequent bone metastasis formation and osteolysis. Furthermore, we are the first to show that anti-c-fms antibodies can impact early establishment of breast cancer cells in bone.

Isotopic Composition of the Neolithic Alpine Iceman's Tooth Enamel and Clues to his Origin

NASA Astrophysics Data System (ADS)

Muller, W.; Muller, W.; Halliday, A. N.

2001-12-01

Five small enamel fragments from three teeth of the upper right jaw from the mummy of the Neolithic Alpine Iceman have been investigated for their isotopic composition in order to shed light on his geographic origins. Soils from approximately contemporaneous sites were sampled for comparison. Tooth enamel forms ontogenetically very early and is not re-mineralized during later lifetime (unlike with bone material). Therefore, unique insights into the Iceman's childhood can be acquired. Enamel also is the densest tissue of a human body and is thus less susceptible to post-mortem alteration. Both radiogenic (Sr, Pb, Nd) and stable isotopes (O, C) are investigated. Radiogenic isotopes allow reconstruction of the local geological background, because humans incorporate Sr, Pb and Nd from their local environment by eating local food. Stable isotopes provide information about altitude and/or position relative to the main Alpine watershed. High spatial-resolution laser-ablation ICPMS profiles reveal that most elements are distributed in a manner that is essentially similar to modern human teeth except of that La, Ce, Nd (LREE) show up to a 100-fold enrichment towards the outer enamel surface. These uptake-profiles may reflect interaction with melt water, consistent with data for the composition of samples of the Iceman's skin. Biogenic apatites (enamel, bone) have very low in-vivo LREE concentrations, but take up LREEs post-mortem from the burial environment. Ice core samples from the finding site show concentrations up to 400 ppt Ce. Such high uptake of the LREEs precludes the derivation of an in-vivo Nd isotopic signal, but both other radiogenic tracers, Sr and Pb, show pristine (in-vivo) concentrations of 87 ppm and 0.1 ppm, respectively. Strontium isotopic compositions were determined on fragments from the canine, the first and second premolar (1 - 9 mg) and two hip bone samples, utilizing three sequential leaching steps for each sample to detect possible alteration-related disturbance. Enamel fragments from three teeth are characterized by virtually similar and high 87Sr/^{86}Sr ratios of 0.7203-0.7206, consistent with the compositions of crystalline gneisses and schists close to the finding site. Sites overlying bedrock built up by limestone from further south or north can clearly be excluded as the Iceman's childhood area. Among the three teeth, enamel mineralized approximately during a 2-3 year interval starting with the canine at the age of ~2 years. Hence, during this period, the food source for the Iceman must have remained essentially constant. Two compact bone samples from the damaged hip region have 87Sr/^{86}Sr ratios of 0.7175 and 0.7181, significantly lower than that of the enamel. The internal variation in the Iceman's bone Sr isotopic composition argues for somewhat different Sr turnover times within the skeleton, but it is evident that during the last 1-3 decades of his life, food from a different region was utilized. The 87Sr/^{86}Sr ratios of the initial bone leachates point towards post-mortem alteration with water having 87Sr/^{86}Sr ratios higher than ~0.718, consistent with that measured for contemporaneous ice samples (0.720-0.723). These Sr isotopic variations among ice samples may have implications for the post depositional (climate) history of the Iceman's finding site, since it appears unlikely that substantial compositional differences among adjacent ice samples would be preserved if the site had thawed near completely during e.g. the Roman warm period.

Two-wave propagation in in vitro swine distal ulna

NASA Astrophysics Data System (ADS)

Mano, Isao; Horii, Kaoru; Matsukawa, Mami; Otani, Takahiko

2015-07-01

Ultrasonic transmitted waves were obtained in an in vitro swine distal ulna specimen, which mimics a human distal radius, that consists of interconnected cortical bone and cancellous bone. The transmitted waveforms appeared similar to the fast waves, slow waves, and overlapping fast and slow waves measured in the specimen after removing the surface cortical bone (only cancellous bone). In addition, the circumferential waves in the cortical bone and water did not affect the fast and slow waves. This suggests that the fast-and-slow-wave phenomenon can be observed in an in vivo human distal radius.

Accuracy of CT-based attenuation correction in PET/CT bone imaging

NASA Astrophysics Data System (ADS)

Abella, Monica; Alessio, Adam M.; Mankoff, David A.; MacDonald, Lawrence R.; Vaquero, Juan Jose; Desco, Manuel; Kinahan, Paul E.

2012-05-01

We evaluate the accuracy of scaling CT images for attenuation correction of PET data measured for bone. While the standard tri-linear approach has been well tested for soft tissues, the impact of CT-based attenuation correction on the accuracy of tracer uptake in bone has not been reported in detail. We measured the accuracy of attenuation coefficients of bovine femur segments and patient data using a tri-linear method applied to CT images obtained at different kVp settings. Attenuation values at 511 keV obtained with a 68Ga/68Ge transmission scan were used as a reference standard. The impact of inaccurate attenuation images on PET standardized uptake values (SUVs) was then evaluated using simulated emission images and emission images from five patients with elevated levels of FDG uptake in bone at disease sites. The CT-based linear attenuation images of the bovine femur segments underestimated the true values by 2.9 ± 0.3% for cancellous bone regardless of kVp. For compact bone the underestimation ranged from 1.3% at 140 kVp to 14.1% at 80 kVp. In the patient scans at 140 kVp the underestimation was approximately 2% averaged over all bony regions. The sensitivity analysis indicated that errors in PET SUVs in bone are approximately proportional to errors in the estimated attenuation coefficients for the same regions. The variability in SUV bias also increased approximately linearly with the error in linear attenuation coefficients. These results suggest that bias in bone uptake SUVs of PET tracers ranges from 2.4% to 5.9% when using CT scans at 140 and 120 kVp for attenuation correction. Lower kVp scans have the potential for considerably more error in dense bone. This bias is present in any PET tracer with bone uptake but may be clinically insignificant for many imaging tasks. However, errors from CT-based attenuation correction methods should be carefully evaluated if quantitation of tracer uptake in bone is important.

Cell Culturing of Cytoskeleton

NASA Technical Reports Server (NTRS)

2004-01-01

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc., has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc., is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Cell Culturing of Cytoskeleton

NASA Technical Reports Server (NTRS)

2004-01-01

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc. has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc. is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

One Million Bones: Measuring the Effect of Human Rights Participation in the Social Work Classroom

ERIC Educational Resources Information Center

McPherson, Jane; Cheatham, Leah P.

2015-01-01

This article describes the integration of human rights content and a national arts-activism initiative--One Million Bones--into a bachelor's-level macro practice class as a human rights teaching strategy. Two previously validated scales, the Human Rights Exposure (HRX) in Social Work and the Human Rights Engagement (HRE) in Social Work (McPherson…

Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.

PubMed Central

Saito, H; Hatake, K; Dvorak, A M; Leiferman, K M; Donnenberg, A D; Arai, N; Ishizaka, K; Ishizaka, T

1988-01-01

Effects of recombinant human interleukins on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical-cord blood and bone marrow. The results showed that interleukin 5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with interleukin 5, essentially all nonadherent cells in both bone marrow and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with interleukin 4 resulted in the selective growth of OKT3+ lymphocytes. However, OKT3+ cells did not develop if the bone marrow cells were depleted of OKT3+/OKT11+ cells prior to the culture, indicating that interleukin 4 induced the proliferation of a subpopulation of resting T cells present in cord blood and bone marrow cell preparations. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of interleukin 3, basophilic, eosinophilic, and neutrophilic myelocytes and macrophages developed within 2 weeks. By 3 weeks, however, the majority of nonadherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither interleukin 3 nor a combination of interleukins 3 and 4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures. Images PMID:3258425

Numerical simulation of stress amplification induced by crack interaction in human femur bone

NASA Astrophysics Data System (ADS)

Alia, Noor; Daud, Ruslizam; Ramli, Mohammad Fadzli; Azman, Wan Zuki; Faizal, Ahmad; Aisyah, Siti

2015-05-01

This research is about numerical simulation using a computational method which study on stress amplification induced by crack interaction in human femur bone. Cracks in human femur bone usually occur because of large load or stress applied on it. Usually, the fracture takes longer time to heal itself. At present, the crack interaction is still not well understood due to bone complexity. Thus, brittle fracture behavior of bone may be underestimated and inaccurate. This study aims to investigate the geometrical effect of double co-planar edge cracks on stress intensity factor (K) in femur bone. This research focuses to analyze the amplification effect on the fracture behavior of double co-planar edge cracks, where numerical model is developed using computational method. The concept of fracture mechanics and finite element method (FEM) are used to solve the interacting cracks problems using linear elastic fracture mechanics (LEFM) theory. As a result, this study has shown the identification of the crack interaction limit (CIL) and crack unification limit (CUL) exist in the human femur bone model developed. In future research, several improvements will be made such as varying the load, applying thickness on the model and also use different theory or method in calculating the stress intensity factor (K).

Effects of caffeic and chlorogenic acids on the rat skeletal system.

PubMed

Folwarczna, J; Pytlik, M; Zych, M; Cegieła, U; Nowinska, B; Kaczmarczyk-Sedlak, I; Sliwinski, L; Trzeciak, H; Trzeciak, H I

2015-02-01

Caffeic acid, predominantly as esters linked to quinic acid (chlorogenic acids), is a phenolic acid present at high levels in coffee. The aim of the study was to investigate effects of caffeic and chlorogenic acids on the skeletal system of female rats with normal estrogen levels and estrogen-deficient. Caffeic acid (5 and 50 mg/kg p.o. daily) and chlorogenic acid (100 mg/kg p.o. daily) were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized mature Wistar rats, and their effects were compared with appropriate controls. Moreover, estradiol (0.2 mg/kg p.o. daily) was administered to ovariectomized rats. Bone turnover markers, mass, mineralization and mechanical properties were examined. Although caffeic acid at a low dose exerted some unfavorable effects on the skeletal system, at high doses, caffeic and chlorogenic acids slightly increased mineralization in the tibia and improved mechanical properties of the femoral diaphysis (compact bone). Unlike estradiol, they did not counteract the worsening of the tibial metaphysis bone strength (cancellous bone) and increases in osteocalcin concentration induced by estrogen deficiency. High doses of the phenolic acids slightly favorably affected the rat skeletal system independently of the estrogen status.

Poly (γ-glutamic acid)/beta-TCP nanocomposites via in situ copolymerization: Preparation and characterization.

PubMed

Shu, Xiu-Lin; Shi, Qing-Shan; Feng, Jin; Yang, Yun-Hua; Zhou, Gang; Li, Wen-Ru

2016-07-01

A series biodegradable poly (γ-glutamic acid)/beta-tricalcium phosphate (γ-PGA/TCP) nanocomposites were prepared which were composed of poly-γ-glutamic acid polymerized in situ with β-tricalcium phosphate and physiochemically characterized as bone graft substitutes. The particle size via dynamic light scattering, the direct morphological characterization via transmission electron microscopy and field emission scanning electron microscope, which showed that γ-PGA and β-TCP were combined compactly at 80℃, and the γ-PGA/TCP nanocomposites had homogenous and nano-sized grains with narrow particle size distributions. The water uptake and retention abilities, in vitro degradation properties, cytotoxicity in the simulated medium, and protein release of these novel γ-PGA/TCP composites were investigated. Cell proliferation in composites was nearly twice than β-TCP when checked in vitro using MC3T3 cell line. We also envision the potential use of γ-PGA/TCP systems in bone growth factor or orthopedic drug delivery applications in future bone tissue engineering applications. These observations suggest that the γ-PGA/TCP are novel nanocomposites with great potential for application in the field of bone tissue engineering. © The Author(s) 2016.

Skeletal age assessment in children using an open compact MRI system.

PubMed

Terada, Yasuhiko; Kono, Saki; Tamada, Daiki; Uchiumi, Tomomi; Kose, Katsumi; Miyagi, Ryo; Yamabe, Eiko; Yoshioka, Hiroshi

2013-06-01

MRI may be a noninvasive and alternative tool for skeletal age assessment in children, although few studies have reported on this topic. In this article, skeletal age was assessed over a wide range of ages using an open, compact MRI optimized for the imaging of a child's hand and wrist, and its validity was evaluated. MR images and their three-dimensional segmentation visualized detailed skeletal features of each bone in the hand and wrist. Skeletal age was then independently scored from the MR images by two raters, according to the Tanner-Whitehouse Japan system. The skeletal age assessed by MR rating demonstrated a strong positive correlation with chronological age. The intrarater and inter-rater reproducibilities were significantly high. These results demonstrate the validity and reliability of skeletal age assessment using MRI. Copyright © 2012 Wiley Periodicals, Inc.

Caspase activity and expression of cell death genes during development of human preimplantation embryos.

PubMed

Spanos, S; Rice, S; Karagiannis, P; Taylor, D; Becker, D L; Winston, R M L; Hardy, K

2002-09-01

It has been observed that apoptosis occurs in human blastocysts. In other types of cell, the characteristic morphological changes seen in apoptotic cells are executed by caspases, which are regulated by the BCL-2 family of proteins. This study investigated whether these components of the apoptotic cascade are present throughout human preimplantation development. Developing and arrested two pronucleate embryos at all stages were incubated with a fluorescently tagged caspase inhibitor that binds only to active caspases, fixed, counterstained with 4,6-diamidino-2-phenylindole (DAPI) to assess nuclear morphology and examined using confocal microscopy. Active caspases were detected only after compaction, at the morula and blastocyst stages, and were frequently associated with apoptotic nuclei. Occasional labelling was seen in arrested embryos. Expression of proapoptotic BAX and BAD and anti-apoptotic BCL-2 was examined in single embryos using RT-PCR and immunohistochemistry. BAX and BCL-2 mRNAs were expressed throughout development, whereas BAD mRNA was expressed mainly after compaction. Simultaneous expression of BAX and BCL-2 proteins within individual embryos was confirmed using immunohistochemistry. The onset of caspase activity and BAD expression after compaction correlates with the previously reported appearance of apoptotic nuclei. As in other types of cell, human embryos express common molecular components of the apoptotic cascade, although apoptosis appears to be suppressed before compaction and differentiation.

Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

PubMed

Hambli, Ridha

2014-01-01

Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone adaptation. The proposed FEM model gives insight into how bone cells adapt their architecture to the mechanical and biological environment.

A concise review of testosterone and bone health

PubMed Central

Mohamad, Nur-Vaizura; Soelaiman, Ima-Nirwana; Chin, Kok-Yong

2016-01-01

Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts. The converted estrogen suppressed osteoclast formation and resorption activity by blocking the receptor activator of nuclear factor k-B ligand pathway. In animal studies, activation of androgen and ERα, but not ERβ, was shown to be important in acquisition and maintenance of bone mass. Human epidemiological studies demonstrated a significant relationship between estrogen and testosterone in bone mineral density and fracture risk, but the relative significance between the two remained debatable. Human experimental studies showed that estrogen was needed in suppressing bone resorption, but both androgen and estrogen were indispensable for bone formation. As a conclusion, maintaining optimal level of androgen is essential in preventing osteoporosis and its complications in elderly men. PMID:27703340

Applicability of cranial models in urethane resin and foam as a substitute for bone: are synthetic materials reliable?

PubMed

Muccino, Enrico; Porta, Davide; Magli, Francesca; Cigada, Alfredo; Sala, Remo; Gibelli, Daniele; Cattaneo, Cristina

2013-09-01

As literature is poor in functional synthetic cranial models, in this study, synthetic handmade models of cranial vaults were produced in two different materials (a urethane resin and a self-hardening foam), from multiple bone specimens (eight original cranial vaults: four human and four swine), in order to test their resemblance to bone structure in behavior, during fracture formation. All the vaults were mechanically tested with a 2-kg impact weight and filmed with a high-speed camera. Fracture patterns were homogeneous in all swine vaults and heterogeneous in human vaults, with resin fractures more similar to bone fractures. Mean fracture latency time extrapolated by videos were of 0.75 msec (bone), 1.5 msec (resin), 5.12 msec (foam) for human vaults and of 0.625 msec (bone), 1.87 msec (resin), 3.75 msec (foam) for swine vaults. These data showed that resin models are more similar to bone than foam reproductions, but that synthetic material may behave quite differently from bone as concerns fracture latency times. © 2013 American Academy of Forensic Sciences.

Different osteochondral potential of clonal cell lines derived from adult human trabecular bone.

PubMed

Osyczka, Anna M; Nöth, Ulrich; Danielson, Keith G; Tuan, Rocky S

2002-06-01

Cells derived from human trabecular bones have been shown to have multipotential differentiation ability along osteogenic, chondrogenic, and adipogenic lineages. In this study, we have derived two clonal sublines of human trabecular bone cells by means of stable transduction with human papilloma virus E6/E7 genes. Our results showed that these clonal sublines differ in their osteochondral potential, but are equally adipogenic, indicative of the heterogeneous nature of the parental cell population. The availability of these cell lines should be useful for the analysis of the mechanisms regulating the differentiation of adult mesenchymal progenitor cells.

Fine mapping of the human bone morphogenetic protein-4 gene (BMP4) to chromosome 14q22-q23 by in situ hybridization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wijngaard, A. van den; Boersma, C.J.C.; Olijve, W.

Bone morphogenetic protein-4 (BMP-4) is a member of the transforming growth factor-{beta} (TGF-{beta}) superfamily and is involved in morphogenesis and bone cell differentiation. Recombinant BMP-4 can induce ectopic cartilage and bone formation when implanted subcutaneously or intramuscularly in rodents. This ectopic bone formation process resembles the process of bone formation during embryogenesis and fracture healing. A cosmid clone containing the complete human bone morphogenetic protein-4 gene (BMP4) was isolated (details to be published elsewhere) and used as a probe to determine the precise chromosomal localization of the human BMP4 gene. This cosmid clone was labeled with biotin-14-dATP and hybridized inmore » situ to chromosomal preparations of metaphase cells as described previously. In 20 metaphase preparations, an intense and specific fluorescence signal (FITC) was detected on the q arm of chromosome 14. The DAPI-counterstained chromosomes were computer-converted into GTG-like banding patterns, allowing the regional localization of BMP4 within 14q22-q23. 10 refs., 1 fig.« less

Human mesenchymal stem cells and biomaterials interaction: a promising synergy to improve spine fusion.

PubMed

Barbanti Brodano, G; Mazzoni, E; Tognon, M; Griffoni, C; Manfrini, M

2012-05-01

Spine fusion is the gold standard treatment in degenerative and traumatic spine diseases. The bone regenerative medicine needs (i) in vitro functionally active osteoblasts, and/or (ii) the in vivo induction of the tissue. The bone tissue engineering seems to be a very promising approach for the effectiveness of orthopedic surgical procedures, clinical applications are often hampered by the limited availability of bone allograft or substitutes. New biomaterials have been recently developed for the orthopedic applications. The main characteristics of these scaffolds are the ability to induce the bone tissue formation by generating an appropriate environment for (i) the cell growth and (ii) recruiting precursor bone cells for the proliferation and differentiation. A new prototype of biomaterials known as "bioceramics" may own these features. Bioceramics are bone substitutes mainly composed of calcium and phosphate complex salt derivatives. In this study, the characteristics bioceramics bone substitutes have been tested with human mesenchymal stem cells obtained from the bone marrow of adult orthopedic patients. These cellular models can be employed to characterize in vitro the behavior of different biomaterials, which are used as bone void fillers or three-dimensional scaffolds. Human mesenchymal stem cells in combination with biomaterials seem to be good alternative to the autologous or allogenic bone fusion in spine surgery. The cellular model used in our study is a useful tool for investigating cytocompatibility and biological features of HA-derived scaffolds.

The behaviour of fatigue-induced microdamage in compact bone samples from control and ovariectomised sheep.

PubMed

Kennedy, Oran D; Brennan, Orlaith; Mauer, Peter; O'Brien, Fergal J; Rackard, Susan M; Taylor, David; Lee, T Clive

2008-01-01

This study investigates the effect of microdamage on bone quality in osteoporosis using an ovariectomised (OVX) sheep model of osteoporosis. Thirty-four sheep were divided into an OVX group (n=16) and a control group (n=18). Fluorochromes were administered intravenously at 3 monthly intervals after surgery to label bone turnover. After sacrifice, beams were removed from the metatarsal and tested in three-point bending. Following failure, microcracks were identified and quantified in terms of region, location and interaction with osteons. Number of cycles to failure (Nf) was lower in the OVX group relative to controls by approximately 7%. Crack density (CrDn) was higher in the OVX group compared to controls. CrDn was 2.5 and 3.5 times greater in the compressive region compared to tensile in control and OVX bone respectively. Combined results from both groups showed that 91% of cracks remained in interstitial bone, approximately 8% of cracks penetrated unlabelled osteons and less than 1% penetrated into labelled osteons. All cases of labelled osteon penetration occurred in controls. Crack surface density (CrSDn), was 25% higher in the control group compared to OVX. It is known that crack behaviour on meeting microstructural features such as osteons will depend on crack length. We have shown that osteon age also affects crack propagation. Long cracks penetrated unlabelled osteons but not labelled ones. Some cracks in the control group did penetrate labelled osteons. This may be due the fact that control bone is more highly mineralized. CrSDn was increased by 25% in the control group compared to OVX. Further study of these fracture mechanisms will help determine the effect of microdamage on bone quality and how this contributes to bone fragility.

The effect of excitation and preparation pulses on nonslice selective 2D UTE bicomponent analysis of bound and free water in cortical bone at 3T

PubMed Central

Li, Shihong; Chang, Eric Y.; Bae, Won C.; Chung, Christine B.; Hua, Yanqing; Zhou, Yi; Du, Jiang

2014-01-01

Purpose: The purpose of this study was to investigate the effect of excitation, fat saturation, long T2 saturation, and adiabatic inversion pulses on ultrashort echo time (UTE) imaging with bicomponent analysis of bound and free water in cortical bone for potential applications in osteoporosis. Methods: Six bovine cortical bones and six human tibial midshaft samples were harvested for this study. Each bone sample was imaged with eight sequences using 2D UTE imaging at 3T with half and hard excitation pulses, without and with fat saturation, long T2 saturation, and adiabatic inversion recovery (IR) preparation pulses. Single- and bicomponent signal models were utilized to calculate the T2*s and/or relative fractions of short and long T2*s. Results: For all bone samples UTE T2* signal decay showed bicomponent behavior. A higher short T2* fraction was observed on UTE images with hard pulse excitation compared with half pulse excitation (75.6% vs 68.8% in bovine bone, 79.9% vs 73.2% in human bone). Fat saturation pulses slightly reduced the short T2* fraction relative to regular UTE sequences (5.0% and 2.0% reduction, respectively, with half and hard excitation pulses for bovine bone, 6.3% and 8.2% reduction, respectively, with half and hard excitation pulses for human bone). Long T2 saturation pulses significantly reduced the long T2* fraction relative to regular UTE sequence (18.9% and 17.2% reduction, respectively, with half and hard excitation pulses for bovine bone, 26.4% and 27.7% reduction, respectively, with half and hard excitation pulses for human bone). With IR-UTE preparation the long T2* components were significantly reduced relative to regular UTE sequence (75.3% and 66.4% reduction, respectively, with half and hard excitation pulses for bovine bone, 87.7% and 90.3% reduction, respectively, with half and hard excitation pulses for human bone). Conclusions: Bound and free water T2*s and relative fractions can be assessed using UTE bicomponent analysis. Long T2* components are affected more by long T2 saturation and IR pulses, and short T2* components are affected more by fat saturation pulses. PMID:24506644

Effects of Age on Bone mRNA Levels of Sclerostin and Other Genes Relevant to Bone Metabolism in Humans

PubMed Central

Roforth, Matthew M.; Fujita, Koji; McGregor, Ulrike I.; Kirmani, Salman; McCready, Louise K.; Peterson, James M.; Drake, Matthew T.; Monroe, David G.; Khosla, Sundeep

2013-01-01

Although aging is associated with a decline in bone formation in humans, the molecular pathways contributing to this decline remain unclear. Several previous clinical studies have shown that circulating sclerostin levels increase with age, raising the possibility that increased production of sclerostin by osteocytes leads to the age-related impairment in bone formation. Thus, in the present study, we examined circulating sclerostin levels as well as bone mRNA levels of sclerostin using quantitative polymerase chain reaction (QPCR) analyses in needle bone biopsies from young (mean age, 30.0 years) versus old (mean age, 72.9 years) women. In addition, we analyzed the expression of genes in a number of pathways known to be altered with skeletal aging, based largely on studies in mice. While serum sclerostin levels were 46% higher (p < 0.01) in the old as compared to the young women, bone sclerostin mRNA levels were no different between the two groups (p = 0.845). However, genes related to notch signaling were significantly upregulated (p = 0.003 when analyzed as a group) in the biopsies from the old women. In an additional analysis of 118 genes including those from genome-wide association studies related to bone density and/or fracture, BMP/TGFβ family genes, selected growth factors and nuclear receptors, and Wnt/Wnt-related genes, we found that mRNA levels of the Wnt inhibitor, SFRP1, were significantly increased (by 1.6-fold, p = 0.0004, false discovery rate [q] = 0.04) in the biopsies from the old as compared to the young women. Our findings thus indicate that despite increases in circulating sclerostin levels, bone sclerostin mRNA levels do not increase in elderly women. However, aging is associated with alterations in several key pathways and genes in humans that may contribute to the observed impairment in bone formation. These include notch signaling, which represents a potential therapeutic target for increasing bone formation in humans. Our studies further identified mRNA levels of SFRP1 as being increased in aging bone in humans, suggesting that this may also represent a viable target for the development of anabolic therapies for age-related bone loss and osteoporosis. PMID:24184314

The effect of excitation and preparation pulses on nonslice selective 2D UTE bicomponent analysis of bound and free water in cortical bone at 3T

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Shihong; Department of Radiology, Hua Dong Hospital, Fudan University, Shanghai 200040; Yancheng Medical College, Jiangsu

Purpose: The purpose of this study was to investigate the effect of excitation, fat saturation, long T2 saturation, and adiabatic inversion pulses on ultrashort echo time (UTE) imaging with bicomponent analysis of bound and free water in cortical bone for potential applications in osteoporosis. Methods: Six bovine cortical bones and six human tibial midshaft samples were harvested for this study. Each bone sample was imaged with eight sequences using 2D UTE imaging at 3T with half and hard excitation pulses, without and with fat saturation, long T2 saturation, and adiabatic inversion recovery (IR) preparation pulses. Single- and bicomponent signal modelsmore » were utilized to calculate the T2{sup *}s and/or relative fractions of short and long T2{sup *}s. Results: For all bone samples UTE T2{sup *} signal decay showed bicomponent behavior. A higher short T2{sup *} fraction was observed on UTE images with hard pulse excitation compared with half pulse excitation (75.6% vs 68.8% in bovine bone, 79.9% vs 73.2% in human bone). Fat saturation pulses slightly reduced the short T2{sup *} fraction relative to regular UTE sequences (5.0% and 2.0% reduction, respectively, with half and hard excitation pulses for bovine bone, 6.3% and 8.2% reduction, respectively, with half and hard excitation pulses for human bone). Long T2 saturation pulses significantly reduced the long T2{sup *} fraction relative to regular UTE sequence (18.9% and 17.2% reduction, respectively, with half and hard excitation pulses for bovine bone, 26.4% and 27.7% reduction, respectively, with half and hard excitation pulses for human bone). With IR-UTE preparation the long T2{sup *} components were significantly reduced relative to regular UTE sequence (75.3% and 66.4% reduction, respectively, with half and hard excitation pulses for bovine bone, 87.7% and 90.3% reduction, respectively, with half and hard excitation pulses for human bone). Conclusions: Bound and free water T2{sup *}s and relative fractions can be assessed using UTE bicomponent analysis. Long T2{sup *} components are affected more by long T2 saturation and IR pulses, and short T2{sup *} components are affected more by fat saturation pulses.« less

Hominid cranial bone structure: a histological study of Omo 1 specimens from Ethiopia using different microscopic techniques.

PubMed

Bartsiokas, Antonis

2002-05-01

The microstructure of a hominid cranial vault has not previously been studied to determine its tissue histology, and differences in comparison with that of modern humans. We selected the parietals of Omo-Kibish 1, regarded as one of the oldest (about 130,000 years old) anatomically modern humans, and Omo 1 (Howell), which is a very recent human (about 2,000 years old)-both from the same area of Ethiopia. A combination of macrophotography, polarizing microscopy in the incident and transmission illumination mode, and confocal laser scanning microscopy (CLSM) was employed to examine thin sections, as well as polished and unpolished block faces of unembedded bone fragments, to minimize specimen destruction as much as possible. The methods enabled remarkably detailed information on bone microstructure and remodeling to be gleaned from tiny fragments of bone. The best method for examining fossilized human bones was shown to be that of incident light microscopy, which was the least destructive while producing the most amount of information. Unless the above methods are used, bone-filling minerals, such as calcite, can cause erroneous estimations of bone thickness, as observations with the naked eye or even a magnifying glass cannot determine the limit between the cortex and the diploe. This is particularly important for sciences such as paleoanthropology, in which, for instance, a thick cranial bone of Homo erectus may be confused with a pathological one of H. sapiens and vice versa. Cross sections of parietal bones revealed differences between Omo-Kibish 1 and Omo 1 (Howell) in diploic histology and in the relative thickness between the cortex and diploe, with the former specimen having an H. erectus ratio despite its H. sapiens gross anatomy. Omo-Kibish 1 may still retain some affinities with H. erectus despite its being classified as H. sapiens. Newly described histological structures, such as the reverse type II osteons, the multicanalled osteons, and the osteocytomata are presented here. A modern human skeletal anatomy does not necessarily imply a modern human cranial bone histology. The outer circumferential lamellae of cranial bones are in essence growth lines. Cranial histology of hominids may provide useful information concerning their taxonomy and life history, including such factors as growth rate, developmental stress, and diet. Copyright 2002 Wiley-Liss, Inc.

Bones, Muscles, and Joints: The Musculoskeletal System

MedlinePlus

... Staying Safe Videos for Educators Search English Español Bones, Muscles, and Joints KidsHealth / For Teens / Bones, Muscles, ... to do everyday physical activities. What Are the Bones and What Do They Do? The human skeleton ...

Synchrotron Study of Strontium in Modern and Ancient Human Bones

NASA Astrophysics Data System (ADS)

Pingitore, N. E.; Cruz-Jimenez, G.

2001-05-01

Archaeologists use the strontium in human bone to reconstruct diet and migration in ancient populations. Because mammals discriminate against strontium relative to calcium, carnivores show lower bone Sr/Ca ratios than herbivores. Thus, in a single population, bone Sr/Ca ratios can discriminate a meat-rich from a vegetarian diet. Also, the ratio of 87-Sr to 86-Sr in soils varies with the underlying geology; incorporated into the food chain, this local signature becomes embedded in our bones. The Sr isotopic ratio in the bones of individuals or populations which migrate to a different geologic terrane will gradually change as bone remodels. In contrast, the isotopic ratio of tooth enamel is fixed at an early age and is not altered later in life. Addition of Sr to bone during post-mortem residence in moist soil or sediment compromises application of the Sr/Ca or Sr-isotope techniques. If this post-mortem Sr resides in a different atomic environment than the Sr deposited in vivo, x-ray absorption spectroscopy could allow us to distinguish pristine from contaminated, and thus unreliable, samples. Initial examination of a suite of modern and ancient human and animal bones by extended x-ray absorption fine structure (EXAFS) showed no obvious differences between the fresh and buried materials. We note, with obvious concern, that the actual location of Sr in modern bone is controversial: there is evidence both that Sr substitutes for Ca and that Sr is sorbed on the surfaces of bone crystallites. Additional material is being studied.

Three-dimensional evaluation of human jaw bone microarchitecture: correlation between the microarchitectural parameters of cone beam computed tomography and micro-computer tomography.

PubMed

Kim, Jo-Eun; Yi, Won-Jin; Heo, Min-Suk; Lee, Sam-Sun; Choi, Soon-Chul; Huh, Kyung-Hoe

2015-12-01

To evaluate the potential feasibility of cone beam computed tomography (CBCT) in the assessment of trabecular bone microarchitecture. Sixty-eight specimens from four pairs of human jaw were scanned using both micro-computed tomography (micro-CT) of 19.37-μm voxel size and CBCT of 100-μm voxel size. The correlation of 3-dimensional parameters between CBCT and micro-CT was evaluated. All parameters, except bone-specific surface and trabecular thickness, showed linear correlations between the 2 imaging modalities (P < .05). Among the parameters, bone volume, percent bone volume, trabecular separation, and degree of anisotropy (DA) of CBCT images showed strong correlations with those of micro-CT images. DA showed the strongest correlation (r = 0.693). Most microarchitectural parameters from CBCT were correlated with those from micro-CT. Some microarchitectural parameters, especially DA, could be used as strong predictors of bone quality in the human jaw. Copyright © 2015 Elsevier Inc. All rights reserved.

The use of bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.

PubMed

Kagami, Hideaki; Agata, Hideki; Inoue, Minoru; Asahina, Izumi; Tojo, Arinobu; Yamashita, Naohide; Imai, Kohzoh

2014-06-01

Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms.

77 FR 19687 - Notice of Inventory Completion: California Department of Parks and Recreation, Sacramento, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

.... At an unknown date in the 1970s, a cremated human bone representing, at minimum, one individual was... 1970s, a cremated human bone representing, at minimum, one individual was removed from site CA-SDI- 1116... seed; 1 green fused shale biface tip; 1 burnt wonderstone flake; 2 burned worked faunal bone fragments...

78 FR 60810 - Change to the Definition of “Human Organ” Under Section 301 of the National Organ Transplant Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... hematopoietic stem cells (HSCs) within peripheral blood in the definition of ``bone marrow.'' This would clarify... of whether they were recovered directly from bone marrow (by aspiration) or from peripheral blood (by... consideration.'' ``Human organ'' is defined to include ``bone marrow * * * or any subpart thereof'' or any organ...

3D porous calcium-alginate scaffolds cell culture system improved human osteoblast cell clusters for cell therapy.

PubMed

Chen, Ching-Yun; Ke, Cherng-Jyh; Yen, Ko-Chung; Hsieh, Hui-Chen; Sun, Jui-Sheng; Lin, Feng-Huei

2015-01-01

Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine. Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge. A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters. The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability. This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation. The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection. The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects.

Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model.

PubMed

Ismail, Tarek; Osinga, Rik; Todorov, Atanas; Haumer, Alexander; Tchang, Laurent A; Epple, Christian; Allafi, Nima; Menzi, Nadia; Largo, René D; Kaempfen, Alexandre; Martin, Ivan; Schaefer, Dirk J; Scherberich, Arnaud

2017-11-01

Avascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. The standard of care, vascularized bone grafts, is limited by donor site morbidity and restricted availability. The aim of this study was to generate and test engineered, axially vascularized SVF cells-based bone substitutes in a rat model of AVN. SVF cells were isolated from lipoaspirates and cultured onto porous hydroxyapatite scaffolds within a perfusion-based bioreactor system for 5days. The resulting constructs were inserted into devitalized bone cylinders mimicking AVN-affected bone. A ligated vascular bundle was inserted upon subcutaneous implantation of constructs in nude rats. After 1 and 8weeks in vivo, bone formation and vascularization were analyzed. Newly-formed bone was found in 80% of SVF-seeded scaffolds after 8weeks but not in unseeded controls. Human ALU+cells in the bone structures evidenced a direct contribution of SVF cells to bone formation. A higher density of regenerative, M2 macrophages was observed in SVF-seeded constructs. In both experimental groups, devitalized bone was revitalized by vascularized tissue after 8 weeks. SVF cells-based osteogenic constructs revitalized fully necrotic bone in a challenging AVN rat model of clinically-relevant size. SVF cells contributed to accelerated initial vascularization, to bone formation and to recruitment of pro-regenerative endogenous cells. Avascular necrosis (AVN) of bone often requires surgical treatment with autologous bone grafts, which is surgically demanding and restricted by significant donor site morbidity and limited availability. This paper describes a de novo engineered axially-vascularized bone graft substitute and tests the potential to revitalize dead bone and provide efficient new bone formation in a rat model. The engineering of an osteogenic/vasculogenic construct of clinically-relevant size with stromal vascular fraction of human adipose, combined to an arteriovenous bundle is described. This construct revitalized and generated new bone tissue. This successful approach proposes a novel paradigm in the treatment of AVN, in which an engineered, vascularized osteogenic graft would be used as a germ to revitalize large volumes of necrotic bone. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Neandertals made the first specialized bone tools in Europe

PubMed Central

Soressi, Marie; McPherron, Shannon P.; Lenoir, Michel; Dogandžić, Tamara; Goldberg, Paul; Jacobs, Zenobia; Maigrot, Yolaine; Martisius, Naomi L.; Miller, Christopher E.; Rendu, William; Richards, Michael; Skinner, Matthew M.; Steele, Teresa E.; Talamo, Sahra; Texier, Jean-Pierre

2013-01-01

Modern humans replaced Neandertals ∼40,000 y ago. Close to the time of replacement, Neandertals show behaviors similar to those of the modern humans arriving into Europe, including the use of specialized bone tools, body ornaments, and small blades. It is highly debated whether these modern behaviors developed before or as a result of contact with modern humans. Here we report the identification of a type of specialized bone tool, lissoir, previously only associated with modern humans. The microwear preserved on one of these lissoir is consistent with the use of lissoir in modern times to obtain supple, lustrous, and more impermeable hides. These tools are from a Neandertal context proceeding the replacement period and are the oldest specialized bone tools in Europe. As such, they are either a demonstration of independent invention by Neandertals or an indication that modern humans started influencing European Neandertals much earlier than previously believed. Because these finds clearly predate the oldest known age for the use of similar objects in Europe by anatomically modern humans, they could also be evidence for cultural diffusion from Neandertals to modern humans. PMID:23940333

21 CFR 892.1180 - Bone sonometer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bone sonometer. 892.1180 Section 892.1180 Food and... RADIOLOGY DEVICES Diagnostic Devices § 892.1180 Bone sonometer. (a) Identification. A bone sonometer is a device that transmits ultrasound energy into the human body to measure acoustic properties of bone that...

21 CFR 892.1180 - Bone sonometer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bone sonometer. 892.1180 Section 892.1180 Food and... RADIOLOGY DEVICES Diagnostic Devices § 892.1180 Bone sonometer. (a) Identification. A bone sonometer is a device that transmits ultrasound energy into the human body to measure acoustic properties of bone that...

21 CFR 892.1180 - Bone sonometer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bone sonometer. 892.1180 Section 892.1180 Food and... RADIOLOGY DEVICES Diagnostic Devices § 892.1180 Bone sonometer. (a) Identification. A bone sonometer is a device that transmits ultrasound energy into the human body to measure acoustic properties of bone that...

Sphene ceramics for orthopedic coating applications: an in vitro and in vivo study.

PubMed

Ramaswamy, Yogambha; Wu, Chengtie; Dunstan, Colin R; Hewson, Benjamin; Eindorf, Tanja; Anderson, Gail I; Zreiqat, Hala

2009-10-01

The host response to titanium alloy (Ti-6Al-4V) is not always favorable as a fibrous layer may form at the skeletal tissue-device interface, causing aseptic loosening. Recently, sphene (CaTiSiO(5)) ceramics were developed by incorporating Ti in the Ca-Si system, and found to exhibit improved chemical stability. The aim of this study is to evaluate the in vitro response of human osteoblast-like cells, human osteoclasts and human microvascular endothelial cells to sphene ceramics and determine whether coating Ti-6Al-4V implants with sphene enhances anchorage to surrounding bone. The study showed that sphene ceramics support human osteoblast-like cell attachment with organized cytoskeleton structure and express increased mRNA levels of osteoblast-related genes. Sphene ceramics were able to induce the differentiation of monocytes to form functional osteoclasts with the characteristic features of f-actin and alpha(v)beta(3) integrin, and express osteoclast-related genes. Human endothelial cells were also able to attach and express the endothelial cell markers ZO-1 and VE-Cadherin when cultured on sphene ceramics. Histological staining, enzyme histochemistry and immunolabelling were used for identification of mineralized bone and bone remodelling around the coated implants. Ti-6Al-4V implants coated with sphene showed new bone formation and filled the gap between the implants and existing bone in a manner comparable to that of the hydroxyapatite coatings used as control. The new bone was in direct contact with the implants, whereas fibrous tissue formed between the bone and implant with uncoated Ti-6Al-4V. The in vivo assessment of sphene-coated implants supports our in vitro observation and suggests that they have the ability to recruit osteogenic cells, and thus support bone formation around the implants and enhance osseointegration.

Steroid and xenobiotic receptor-mediated effects of bisphenol A on human osteoblasts.

PubMed

Miki, Yasuhiro; Hata, Shuko; Nagasaki, Shuji; Suzuki, Takashi; Ito, Kiyoshi; Kumamoto, Hiroyuki; Sasano, Hironobu

2016-06-15

Bisphenol A, one of the industrial chemicals used in plastics and in the coating of dishes and medical equipment, behaves as an endocrine disruptor in the human body. Bisphenol A can bind directly to several types of nuclear receptors, including steroid and xenobiotic receptor (SXR). SXR plays an important role in bone metabolism through the activation of osteoblasts in vitro, but SXR protein localization has not been reported in bone tissues. Additionally, it is not known whether bisphenol A acts on osteoblasts through SXR activation. Therefore, in this study, we first examined the immunolocalization of the SXR protein in human adult and fetal bone tissues. We then examined the effects of bisphenol A on human osteoblasts in vitro. SXR immunoreactivity was detected in osteoblasts, but not in osteoclasts, of both adult and fetal bone tissues. In fetal bone tissues, the mesenchymal cells or fetal connective tissue were also positive for SXR immunoreactivity. Expression of SXR target genes (tsukushi, matrilin-2, and CYP3A4) and SXR response element-luciferase activity were increased by bisphenol A treatment in normal osteoblasts transfected with SXR (hFOB/SXR) and in osteoblast-like cells (MG-63). Bisphenol A also stimulated cell proliferation and collagen accumulation in hFOB/SXR cells. These results suggest that, as in other tissues, SXR plays important roles in bone metabolism and fetal bone development and that bisphenol A may disturb bone homeostasis in both adult and fetus through SXR. Copyright © 2016 Elsevier Inc. All rights reserved.

The Use of Recombinant Human Platelet-Derived Growth Factor for Maxillary Sinus Augmentation.

PubMed

Kubota, Atsushi; Sarmiento, Hector; Alqahtani, Mohammed Saad; Llobell, Arturo; Fiorellini, Joseph P

The maxillary sinus augmentation procedure has become a predictable treatment to regenerate bone for implant placement. The purpose of this study was to evaluate the effect of recombinant human platelet-derived growth factor BB (rhPDGF-BB) combined with a deproteinized cancellous bovine bone graft for sinus augmentation. The lateral window approach was used for maxillary sinuses with minimal residual bone. After a healing period of 4 months, dental implants were placed and then restored following a 2-month osseointegration period. The result demonstrated increased bone height and ISQ values and a 100% survival rate. This study indicates that the addition of rhPDGF-BB to deproteinized cancellous bovine bone accelerated the healing period in maxillary sinuses with minimal native bone.

Preparation and characterization of calcium phosphate ceramics and composites as bone substitutes

NASA Astrophysics Data System (ADS)

Zhang, Xing

Marine CaCO3 skeletons have tailored architectures created by nature, which give them structural support and other functions. For example, seashells have dense lamellar structures, while coral, cuttlebone and sea urchin spines have interconnected porous structures. In our experiments, seashells, coral and cuttlebone were hydrothermally converted to hydroxyapatite (HAP), and sea urchin spines were converted to Mg-substituted tricalcium phosphate (beta-TCMP), while maintaining their original structures. Partially converted shell samples have mechanical strength, which is close to that of compact human bone. After implantation of converted shell and spine samples in rat femoral defects for 6 weeks, there was newly formed bone growth up to and around the implants. Some new bone was found to migrate through the pores of converted spine samples and grow inward. These results show good bioactivity and osteoconductivity of the implants, indicating the converted shell and spine samples can be used as bone defect fillers. Calcium phosphate powders were prepared through different synthesis methods. Micro-size HAP rods were synthesized by hydrothermal method through a nucleation-growth mechanism. On the other hand, HAP particles, which have good crystallinity, were prepared by wet precipitation with further hydrothermal treatment. beta-TCP or beta-TCMP powders were prepared by a two-step process: wet precipitation of apatitic tricalcium phosphate ('precursor') and calcination of the precursor at 800°C for 3 hours. beta-TCMP or beta-TCP powders were also prepared by solid-state reactions from CaHPO4 and CaCO 3 with/without MgO. Biphasic calcium phosphate, which is mixture of HAP and beta-TCP, can be prepared though mechanical mixing of HAP and beta-TCP powders synthesized as above. Dense beta-TCP and beta-TCMP ceramics can be produced by pressing green bodies at 100MPa and further sintering above 1100°C for 2 hours. beta-TCMP ceramics ˜99.4% relative dense were prepared by this method. Dense beta-TCP ceramics have average strength up to 540MPa. Macroporous beta-TCMP ceramics were produced with sucrose as the porogen following a two-step pressing method. Porous beta-TCMP ceramics were also prepared by replication of polyurethane sponge. beta-TCMP ceramics with porous structures in the center surrounded by dense structures were created. The outside dense structures give the scaffold mechanical strength, while the central porous structures enable cells migration and vascular infiltration, and finally in-growth of new bone into the scaffold.

Multi-scale osteointegration and neovascularization of biphasic calcium phosphate bone scaffolds

NASA Astrophysics Data System (ADS)

Lan, Sheeny K.

Bone grafts are utilized clinically to guide tissue regeneration. Autologous bone and allogeneic bone are the current clinical standards. However, there are significant limitations to their use. To address the need for alternatives to autograft and allograft, researchers have worked to develop synthetic grafts, also referred to as scaffolds. Despite extensive efforts in this area, a gap persists between basic research and clinical application. In particular, solutions for repairing critical size and/or load-bearing defects are lacking. The aim of this thesis work was to address two critical barriers preventing design of successful tissue engineering constructs for bone regeneration within critical size and/or load-bearing defects. Those barriers are insufficient osteointegration and slow neovascularization. In this work, the effects of scaffold microporosity, recombinant human bone morphogenetic protein-2 delivery and endothelial colony forming cell vasculogenesis were evaluated in the context of bone formation in vivo. This was accomplished to better understand the role of these factors in bone regeneration, which may translate to improvements in tissue engineering construct design. Biphasic calcium phosphate (BCP) scaffolds with controlled macro- and microporosity were implanted in porcine mandibular defects. Evaluation of the BCP scaffolds after in vivo implantation showed, for the first time, osteocytes embedded in bone within scaffold micropores (< 10 microm) as well as the most extensive bone growth into micropores to date with bone penetration throughout rods 394 microm in diameter. The result is the first truly osteointegrated bone scaffolds with integration occurring at both the macro and micro length scales, leaving no "dead space" or discontinuities of bone in the defect site. The scaffold forms a living composite upon integration with regenerating bone and this has significant implications with regard to improved scaffold mechanical properties. The presence of osteocytes within scaffold micropores is an indication of scaffold osteoinductivity because a chemotactic factor must be present to induce cell migration into pores on the order of the cell diameter. It is likely that the scaffold undergoes in vivo modifications involving formation of a biological apatite layer within scaffold micropores and possibly co-precipitation of endogenous osteoinductive proteins. To further investigate the effects of scaffold osteoinductivity, BCP scaffolds were implanted in porcine mandibular defects with rhBMP-2, which was partially sequestered in the micropores. Cell migration into osteoinductive scaffold micropores can be enhanced through the delivery of exogenous rhBMP-2 further promoting multi-scale osteointegration. Finally, endothelial colony forming cells (ECFCs) isolated from human umbilical cord blood (UCB) were evaluated in terms of their in vivo vasculogenic potential in the context of bone formation. This work was completed to determine if ECFCs could be utilized in a bone tissue engineering construct to promote neovascularization. ECFCs were combined with a BCP scaffold and rhBMP-2 and implanted subcutaneously on the abdominal wall of NOD/SCID mice. The result was formation of perfused human vessels within BCP scaffold macropores that were present at 4 weeks. The high density and persistence of human vessels at four weeks indicates that human UCB ECFCs exceed their reported in vivo vasculogenic potential when combined with rhBMP-2 and a BCP scaffold. This shows a dual role for BMP-2 in the context of bone regeneration. Collectively, the thesis demonstrates that (1) the design of synthetic bone scaffolds should include controlled multi-scale porosity to promote multi-scale osteointegration, which may significantly improve scaffold mechanical properties and (2) human umbilical cord blood-derived endothelial colony forming cells have potential for promoting neovascularization in a bone defect when combined with rhBMP-2.

The activity ratio of 228Th to 228Ra in bone tissue of recently deceased humans: a new dating method in forensic examinations.

PubMed

Zinka, Bettina; Kandlbinder, Robert; Schupfner, Robert; Haas, Gerald; Wolfbeis, Otto S; Graw, Matthias

2012-01-01

Reliable determination of time since death in human skeletons or single bones often is limited by methodically difficulties. Determination of the specific activity ratio of natural radionuclides, in particular of 232Th (Thorium), 228Th and 228Ra (Radium) seems to be a new appropriate method to calculate the post mortem interval. These radionuclides are incorporated by any human being, mainly from food. So with an individual's death the uptake of radionuclides ends. But the decay of 232Th produces 228Ra and 228Th due to its decay series, whereas 228Th is continuously built up in the human's bones. Thus, it can be concluded that in all deceased humans at different times after death different activity ratios of 228Th to 228Ra will develop in bone. According to this fact it should be possible to calculate time since death of an individual by first analysing the specific activities of 228Th and 228Ra in bones of deceased and then determining the 228Th/228Ra activity ratio, which can be assigned to a certain post-mortem interval.

Direct cytotoxicity evaluation of 63S bioactive glass and bone-derived hydroxyapatite particles using yeast model and human chondrocyte cells by microcalorimetry.

PubMed

Doostmohammadi, A; Monshi, A; Fathi, M H; Karbasi, S; Braissant, O; Daniels, A U

2011-10-01

In this study, the cytotoxicity evaluation of prepared 63S bioactive glass and bone-derived hydroxyapatite particles with yeast and human chondrocyte cells was carried out using isothermal micro-nano calorimetry (IMNC), which is a new method for studying cell/biomaterial interactions. Bioactive glass particles were made via sol-gel method and hydroxyapatite was obtained from bovine bone. Elemental analysis was carried out by XRF and EDXRF. Amorphous structure of the glass and completely crystalline structure of HA were detected by XRD analysis. Finally, the cytotoxicity of bioactive glass and bone-derived HA particles with yeast and cultured human chondrocyte cells was evaluated using IMNC. The results confirmed the viability, growth and proliferation of human chondrocyte cells in contact with 63S bioactive glass, and bone-derived HA particles. Also the results indicated that yeast model which is much easier to handle, can be considered as a good proxy and can provide a rapid primary estimate of the ranges to be used in assays involving human cells. All of these results confirmed that IMNC is a convenient method which caters to measuring the cell-biomaterial interactions alongside the current methods.

Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

PubMed

Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

2015-06-25

Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites. © 2015 by The American Society of Hematology.

Fabrication of Metallic Biomedical Scaffolds with the Space Holder Method: A Review

PubMed Central

Arifvianto, Budi; Zhou, Jie

2014-01-01

Bone tissue engineering has been increasingly studied as an alternative approach to bone defect reconstruction. In this approach, new bone cells are stimulated to grow and heal the defect with the aid of a scaffold that serves as a medium for bone cell formation and growth. Scaffolds made of metallic materials have preferably been chosen for bone tissue engineering applications where load-bearing capacities are required, considering the superior mechanical properties possessed by this type of materials to those of polymeric and ceramic materials. The space holder method has been recognized as one of the viable methods for the fabrication of metallic biomedical scaffolds. In this method, temporary powder particles, namely space holder, are devised as a pore former for scaffolds. In general, the whole scaffold fabrication process with the space holder method can be divided into four main steps: (i) mixing of metal matrix powder and space-holding particles; (ii) compaction of granular materials; (iii) removal of space-holding particles; (iv) sintering of porous scaffold preform. In this review, detailed procedures in each of these steps are presented. Technical challenges encountered during scaffold fabrication with this specific method are addressed. In conclusion, strategies are yet to be developed to address problematic issues raised, such as powder segregation, pore inhomogeneity, distortion of pore sizes and shape, uncontrolled shrinkage and contamination. PMID:28788638

Computer-aided surgical planner for a new bone deformity correction device using axis-angle representation.

PubMed

Wu, Ying Ying; Plakseychuk, Anton; Shimada, Kenji

2014-11-01

Current external fixators for distraction osteogenesis (DO) are unable to correct all types of deformities in the lower limb and are difficult to use because of the lack of a pre-surgical planning system. We propose a DO system that consists of a surgical planner and a new, easy-to-setup unilateral fixator that not only corrects all lower limb deformity, but also generates the contralateral/predefined bone shape. Conventionally, bulky constructs with six or more joints (six degrees of freedom, 6DOF) are needed to correct a 3D deformity. By applying the axis-angle representation, we can achieve that with a compact construct with only two joints (2DOF). The proposed system makes use of computer-aided design software and computational methods to plan and simulate the planned procedure. Results of our stress analysis suggest that the stiffness of our proposed fixator is comparable to that of the Orthofix unilateral external fixator. We tested the surgical system on a model of an adult deformed tibia and the resulting bone trajectory deviates from the target bone trajectory by 1.8mm, which is below our defined threshold error of 2mm. We also extracted the transformation matrix that defines the deformity from the bone model and simulated the planned procedure. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Dependence of Long Bone Flexural Properties on Bone Mineral Distribution

NASA Technical Reports Server (NTRS)

Katz, BethAnn; Cleek, Tammy M.; Whalen, Robert T.; Connolly, James P. (Technical Monitor)

1995-01-01

The objective of this study is to assess whether a non-invasive determination of long bone cross-sectional areal properties using bone densitometry accurately estimates true long bone flexural properties. In this study, section properties of two pairs of human female embalmed tibiae were compared using two methods: special analysis of bone densitometry data, and experimental determination of flexural regidities from bone surface strain measurements during controlled loading.

Locating the scala media in the fixed human temporal bone for therapeutic access: a preliminary study.

PubMed

Pau, H; Fagan, P; Oleskevich, S

2006-11-01

To investigate the location of the scala media in relation to the round window niche in human temporal bones. Ten human temporal bones were investigated by radical mastoidectomy and promontory drill-out. Temporal bone laboratory. The distance from the scala media to the anterior edge of the round window niche, measured by Fisch's stapedectomy measuring cylinders. The scala media was identified at the transection point of a vertical line 1.6 to 2.2 mm (mean=1.8 mm; standard deviation=0.2) anterior to the anterior edge of the round window niche and a horizontal line 0.2 mm inferior to the lower border of the oval window. This report demonstrates the point of entry into the scala media via the promontory in fixed temporal bone models, which may provide a site of entry for stem cells and gene therapy insertion.

Age and sex bias in the reconstruction of past population structures.

PubMed

Bello, Silvia M; Thomann, Aminte; Signoli, Michel; Dutour, Olivier; Andrews, Peter

2006-01-01

Palaeodemographical studies are founded on the assumption that the sex and age distribution of the skeletal sample reflects the constitution of the original population. It is becoming increasingly clear, however, that the type and amount of information that may be derived from osteoarchaeological collections are related to the state of preservation of remains. This work proposes a new method to evaluate bone preservation, to identify age and sex biases in the preservation of human skeletal remains, and to assess whether differences in preservation patterns are more dependent on factors intrinsic or extrinsic to anatomical features of human bones. Three osteological collections and over 600 skeletons were observed. The state of preservation of human bones was assessed using three preservation indexes: the anatomical preservation index (API), the bone representation index (BRI), and the qualitative bone index (QBI). The results suggest that subadult skeletons are generally more poorly preserved and with bones less well-represented than adult skeletons. Among subadults, female and male skeletons have different patterns of preservation according to their age. This pattern of preservation depends on intrinsic anatomical properties of bones themselves, while external factors can only increase these differences in the state of preservation and representation of osseous remains. It is concluded from this that failure to recognize these differences may lead to misleading interpretations of paleodemography of past human populations.

Synchrotron Radiation and Energy Dispersive X-Ray Fluorescence Applications on Elemental Distribution in Human Hair and Bones

NASA Astrophysics Data System (ADS)

Carvalho, M. L.; Marques, A. F.; Brito, J.

2003-01-01

This work is an application of synchrotron microprobe X- Ray fluorescence in order to study elemental distribution along human hair samples of contemporary citizens. Furthermore, X-Ray fluorescence spectrometry is also used to analyse human bones of different historical periods: Neolithic and contemporary subjects. The elemental content in the bones allowed us to conclude about environmental contamination, dietary habits and health status influence in the corresponding citizens. All samples were collected post-mortem. Quantitative analysis was performed for Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr and Pb. Mn and Fe concentration were much higher in bones from pre-historic periods. On the contrary, Pb bone concentrations of contemporary subjects are much higher than in pre-historical ones, reaching 100 μg g-1, in some cases. Very low concentrations for Co, Ni, Br and Rb were found in all the analysed samples. Cu concentrations, allows to distinguish Chalcolithic bones from the Neolithic ones. The distribution of trace elements along human hair was studied for Pb and the obtained pattern was consistent with the theoretical model, based on the diffusion of this element from the root and along the hair. Therefore, the higher concentrations in hair for Pb of contemporary individuals were also observed in the bones of citizens of the same sampling sites. All samples were analysed directly without any chemical treatment.

Automatic and hierarchical segmentation of the human skeleton in CT images.

PubMed

Fu, Yabo; Liu, Shi; Li, Harold; Yang, Deshan

2017-04-07

Accurate segmentation of each bone of the human skeleton is useful in many medical disciplines. The results of bone segmentation could facilitate bone disease diagnosis and post-treatment assessment, and support planning and image guidance for many treatment modalities including surgery and radiation therapy. As a medium level medical image processing task, accurate bone segmentation can facilitate automatic internal organ segmentation by providing stable structural reference for inter- or intra-patient registration and internal organ localization. Even though bones in CT images can be visually observed with minimal difficulty due to the high image contrast between the bony structures and surrounding soft tissues, automatic and precise segmentation of individual bones is still challenging due to the many limitations of the CT images. The common limitations include low signal-to-noise ratio, insufficient spatial resolution, and indistinguishable image intensity between spongy bones and soft tissues. In this study, a novel and automatic method is proposed to segment all the major individual bones of the human skeleton above the upper legs in CT images based on an articulated skeleton atlas. The reported method is capable of automatically segmenting 62 major bones, including 24 vertebrae and 24 ribs, by traversing a hierarchical anatomical tree and by using both rigid and deformable image registration. The degrees of freedom of femora and humeri are modeled to support patients in different body and limb postures. The segmentation results are evaluated using the Dice coefficient and point-to-surface error (PSE) against manual segmentation results as the ground-truth. The results suggest that the reported method can automatically segment and label the human skeleton into detailed individual bones with high accuracy. The overall average Dice coefficient is 0.90. The average PSEs are 0.41 mm for the mandible, 0.62 mm for cervical vertebrae, 0.92 mm for thoracic vertebrae, and 1.45 mm for pelvis bones.

Automatic and hierarchical segmentation of the human skeleton in CT images

NASA Astrophysics Data System (ADS)

Fu, Yabo; Liu, Shi; Li, H. Harold; Yang, Deshan

2017-04-01

Accurate segmentation of each bone of the human skeleton is useful in many medical disciplines. The results of bone segmentation could facilitate bone disease diagnosis and post-treatment assessment, and support planning and image guidance for many treatment modalities including surgery and radiation therapy. As a medium level medical image processing task, accurate bone segmentation can facilitate automatic internal organ segmentation by providing stable structural reference for inter- or intra-patient registration and internal organ localization. Even though bones in CT images can be visually observed with minimal difficulty due to the high image contrast between the bony structures and surrounding soft tissues, automatic and precise segmentation of individual bones is still challenging due to the many limitations of the CT images. The common limitations include low signal-to-noise ratio, insufficient spatial resolution, and indistinguishable image intensity between spongy bones and soft tissues. In this study, a novel and automatic method is proposed to segment all the major individual bones of the human skeleton above the upper legs in CT images based on an articulated skeleton atlas. The reported method is capable of automatically segmenting 62 major bones, including 24 vertebrae and 24 ribs, by traversing a hierarchical anatomical tree and by using both rigid and deformable image registration. The degrees of freedom of femora and humeri are modeled to support patients in different body and limb postures. The segmentation results are evaluated using the Dice coefficient and point-to-surface error (PSE) against manual segmentation results as the ground-truth. The results suggest that the reported method can automatically segment and label the human skeleton into detailed individual bones with high accuracy. The overall average Dice coefficient is 0.90. The average PSEs are 0.41 mm for the mandible, 0.62 mm for cervical vertebrae, 0.92 mm for thoracic vertebrae, and 1.45 mm for pelvis bones.

Small Molecule Protection of Bone Marrow Hematopoietic Stem Cells

DTIC Science & Technology

2017-12-01

using isogenic (mutant/complemented) human cell line pairs from patients with Fanconi anemia (FA), a heritable human bone marrow failure (BMF) syndrome ...small molecules could be therapeutically useful in reducing the risk of BMF in diseases such as Fanconi anemia, and perhaps after radiation exposure...damage-repair, DNA damage response, Fanconi anemia and associated bone marrow failure syndromes and environmental and molecular toxicology will all be

A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover.

PubMed

Horwitz, Mara J; Tedesco, Mary Beth; Sereika, Susan M; Prebehala, Linda; Gundberg, Caren M; Hollis, Bruce W; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Carneiro, Raquel M; Stewart, Andrew F

2011-09-01

Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM), or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed 7-day continuous-infusion models using human parathyroid hormone(1-34) [hPTH(1-34)] and human parathyroid hormone-related protein(1-36) [hPTHrP(1-36)] in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dL), with marked suppression of endogenous PTH(1-84). The maximal tolerated infused doses over a 7-day period (2 and 4 pmol/kg/h for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8 to 28 pmol/kg/h). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] and tubular maximum for phosphorus (TmP/GFR) remained unaltered with these low doses despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30% to 40% for the 7 days of the infusions. With cessation of PTH and PTHrP infusion, bone-formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone-resorption program but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions are reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT. Copyright © 2011 American Society for Bone and Mineral Research.

Use of Bioresorbable Hydrogels and Genetic Engineering to Accomplish Rapid Stabilization and Healing in Segmental Long Bone Defects

DTIC Science & Technology

2013-04-29

transduction of human mesenchymal stem cells (MSCs), BMP2 was not detectable by Western blotting, whereas high levels of the protein were produced by A549 (human... mesenchymal stem cells , generating high levels of BMP2. When Ad5BMP2 or Ad5F35BMP2 were compared in vitro for their ability to induce BMP2 synthesis...in human mesenchymal stem cells and in vivo for their ability to stimulate formation of heterotopic bone, mineralized bone was radiologically

Impacts of the N-terminal fragment analog of human parathyroid hormone on structure, composition and biomechanics of bone.

PubMed

Chunxiao, Wang; Yu, Zhang; Wentao, Liu; Jingjing, Liu; Jiahui, Ye; Qingmei, Chen

2012-12-18

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, and it is a serious threat to human lives. We previously showed that the N-terminal peptide analog of human parathyroid hormone (Pro-Pro-PTH(1-34)) enhanced plasma calcium concentration. In this paper, we study the impact of PTH N-terminal fragment analog on the structure, component, and mechanical properties of the rat bones. Daily subcutaneous injections of Pro-Pro-hPTH (1-34) induces 26.5-32.8% increase in femur bone mineral density (BMD), 23.0-34.2% decrease the marrow cavity or increase in trabecular bone area. The peptide also increases 16.0-59.5%, 28.8-48.2% and 14.0-17.8% of bone components of calcium, phosphorus and collagen, respectively. In terms of mechanic properties, administration of the peptide elevates the bone rigidity by 45.4-76.6%, decreases the flexibility by 23.0-31.6%, and improves modulus of elasticity by 32.8-63.4%. The results suggest that Pro-Pro-hPTH (1-34) has a positive effect on bone growth and strength, and possesses anti-fracture capability, thus a potential candidate for the application for the treatment of osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of bone sialoprotein coating of ceramic and synthetic polymer materials on in vitro osteogenic cell differentiation and in vivo bone formation.

PubMed

Schaeren, Stefan; Jaquiéry, Claude; Wolf, Francine; Papadimitropoulos, Adam; Barbero, Andrea; Schultz-Thater, Elke; Heberer, Michael; Martin, Ivan

2010-03-15

In this study, we addressed whether Bone Sialoprotein (BSP) coating of various substrates could enhance the in vitro osteogenic differentiation and in vivo bone formation capacity of human Bone Marrow Stromal Cells (BMSC). Moreover, we tested whether synthetic polymer-based porous scaffolds, despite the absence of a mineral component, could support ectopic bone formation by human BMSC if coated with BSP. Adsorption of recombinant human BSP on tissue culture-treated polystyrene (TCTP), beta-tricalcium phosphate (Osteologic) or synthetic polymer (Polyactive) substrates was dose dependent, but did not consistently accelerate or enhance in vitro BMSC osteogenic differentiation, as assessed by the mRNA expression of osteoblast-related genes. Similarly, BSP coating of porous beta-tricalcium phosphate scaffolds (Skelite) did not improve the efficiency of bone tissue formation following loading with BMSC and ectopic implantation in nude mice. Finally, Polyactive foams seeded with BMSC did not form bone tissue in the same ectopic assay, even if coated with BSP. We conclude that BSP coating of a variety of substrates is not directly associated with an enhancement of osteoprogenitor cell differentiation in vitro or in vivo, and that presentation of BSP on polymeric materials is not sufficient to prime BMSC functional osteoblastic differentiation in vivo. (c) 2009 Wiley Periodicals, Inc.

A Direct Role of Collagen Glycation in Bone Fracture

PubMed Central

Poundarik, Atharva A.; Wu, Ping-Cheng; Evis, Zafer; Sroga, Grazyna E.; Ural, Ani; Rubin, Mishaela; Vashishth, Deepak

2015-01-01

Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone’s organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagen’s ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000–5000 μstrain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk. PMID:26530231

Phenomenon of formation of giant fat-containing cells in human bone marrow cultures induced by human serum factor: normal and leukemic patterns.

PubMed

Svet-Moldavskaya, I A; Zinzar, S N; Svet-Moldavsky, G J; Arlin, Z; Vergara, C; Koziner, B; Clarkson, B D; Holland, J F

1983-08-01

Normal human sera induce the formation of fat-containing cells (FCC) in human bone marrow cultures. A nearly complete monolayer of FCC is formed after 7-14 days of cultivation with 20% human sera in the medium. FCC-inducing activity (FCCIA) is nondialyzable through 14,900-dalton cutoff membrane and is stable at 56 degrees C for 30 min. Abundant FCCIA was found in 83% of normal human sera but in only 20% of sera from untreated patients with different hemopoietic disorders and in 32% of treated leukemic patients. It is suggested that FCCIA may be involved in regulation of the bone marrow microenvironment an that it varies in normal individuals and in patients with different diseases.

Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

PubMed

Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A

2004-08-27

The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.

The character of gene expression of human periosteum used to form new tissue in allograft bone.

PubMed

Kemppainen, Jessica; Yu, Qing; Alexander, John; Jacquet, Robin; Scharschmidt, Thomas; Landis, William

2014-08-01

Of more than 2 million segmental bone defects repaired annually with bone autografts and allografts, 15-40% fail. Improving healing rates may be approached with tissue engineering and use of periosteum overlying an allograft. The present study documents gene expression in human periosteum-allograft constructs compared to allografts alone. Strips of human cadaveric periosteum (26 years, f, distal femur) were sutured about sterilized human femoral cortical strut bone allograft (54 years, m) segments. After construct incubation (M199 supplemented medium) for 8 d, constructs and allografts alone were implanted in nude mice. At 10 and 20 weeks, constructs (N = 4, each group) and allografts (N = 2, each group) were retrieved and placed in RNAlater for quantitative PCR to determine expression of human- and murine-specific genes relevant to remodeling. Specimens were frozen-ground to powders and RNA was extracted, purified, reverse-transcribed, and amplified. Ribosomal protein (P0) was used to normalize sample quantities. Fold change plots were generated following statistical analyses comparing 20- to 10-week gene expression data. Allografts alone yielded no human-specific gene expression. Notable fold changes of human-specific alkaline phosphatase, bone sialoprotein, type I collagen, decorin, RANKL, RANK, cathepsin K, and osteocalcin in 20-week compared to 10-week specimens were found. Murine-specific expression of genes indicative of host mouse vascularization (RANK, type I collagen) was detected in both allograft alone and periosteum-allograft samples. Gene data confirm viable periosteum in constructs after 20 weeks. Relatively higher fold-change values of RANK, RANKL and cathepsin K indicate activities of osteoclast precursors, osteoclasts and osteoblasts involved in allograft remodeling during implantation. All additional genes of interest indicate osteoblast activity in new bone matrix formation. Gene data are directly correlated with previous and present histology work. The results of this study suggest that further investigations could help to establish whether autologous periosteum-allograft constructs could be used for the repair of bone defects.

Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

PubMed

Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

2015-12-01

Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Microarchitecture and Bone Quality in the Human Calcaneus; Local Variations of Fabric Anisotropy

PubMed Central

Souzanchi, M F; Palacio-Mancheno, P E; Borisov, Y; Cardoso, L; Cowin, SC

2012-01-01

The local variability of microarchitecture of human trabecular calcaneus bone is investigated using high resolution microCT scanning. The fabric tensor is employed as the measure of the microarchitecture of the pore structure of a porous medium. It is hypothesized that a fabric tensor-dependent poroelastic ultrasound approach will more effectively predict the data variance than will porosity alone. The specific aims of the present study are i) to quantify the morphology and local anisotropy of the calcaneus microarchitecture with respect to anatomical directions, ii) to determine the interdependence, or lack thereof, of microarchitecture parameters, fabric, and volumetric bone mineral density (vBMD), and iii) to determine the relative ability of vBMD and fabric measurements in evaluating the variance in ultrasound wave velocity measurements along orthogonal directions in the human calcaneus. Our results show that the microarchitecture in the analyzed regions of human calcanei is anisotropic, with a preferred alignment along the posterior-anterior direction. Strong correlation was found between most scalar architectural parameters and vBMD. However, no statistical correlation was found between vBMD and the fabric components, the measures of the pore microstructure orientation. Therefore, among the parameters usually considered for cancellous bone (i.e., classic histomorphometric parameters such as porosity, trabecular thickness, number and separation), only fabric components explain the data variance that cannot be explained by vBMD, a global mass measurement, which lacks the sensitivity and selectivity to distinguish osteoporotic from healthy subjects because it is insensitive to directional changes in bone architecture. This study demonstrates that a multi-directional, fabric-dependent poroelastic ultrasound approach has the capability of characterizing anisotropic bone properties (bone quality) beyond bone mass, and could help to better understand anisotropic changes in bone architecture using ultrasound. PMID:22807141

Icaritin, a novel plant-derived osteoinductive agent, enhances the osteogenic differentiation of human bone marrow- and human adipose tissue-derived mesenchymal stem cells.

PubMed

Wu, Tao; Shu, Tao; Kang, Le; Wu, Jinhui; Xing, Jianzhou; Lu, Zhiqin; Chen, Shuxiang; Lv, Jun

2017-04-01

For the treatment of diseases affecting bones using bone regenerative medicine, there is an urgent need to develop safe, inexpensive drugs that can strongly induce bone formation. In the present study, we systematically investigated the effects of icaritin, a metabolic product of icariin, on the osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells (hBMSCs) and human adipose tissue‑derived stem cells (hADSCs) in vitro. After treatment with icaritin at concentrations of 10‑8-10‑5 M, hBMSCs and hADSCs were examined for alkaline phosphatase activity, osteocalcin (OC) secretion, matrix mineralization and expression levels of bone‑related mRNA and proteins. Data showed that icaritin at concentrations 10‑7-10‑5 M significantly increased alkaline phosphatase activity, OC secretion at different time points, and calcium deposition at day 21. In addition, icaritin upregulated the mRNA expression of genes for bone morphogenetic proteins (BMP‑2, ‑4 and ‑7), bone transcription factors (Runx2 and Dlx5) and bone matrix proteins (ALP, OC and Col‑1). Moreover, icaritin increased the protein levels of BMPs, Runx2 and OC, as detected by western blot analysis. These findings suggest that icaritin enhances the osteogenic differentiation of hBMSCS and hADSCs. Icaritin exerts its potent osteogenic effect possibly by directly stimulating the production of BMPs. Although the osteogenic activity of icaritin in vitro was inferior to that of rhBMP‑2, icaritin displayed better results than icariin. Moreover, the low cost, simple extraction procedure, and an abundance of icaritin make it appealing as a bone regenerative medicine.

Interaction between tumor cell surface receptor RAGE and proteinase 3 mediates prostate cancer metastasis to bone

PubMed Central

Kolonin, Mikhail G.; Sergeeva, Anna; Staquicini, Daniela I.; Smith, Tracey L.; Tarleton, Christy A.; Molldrem, Jeffrey J.; Sidman, Richard L.; Marchiò, Serena; Pasqualini, Renata; Arap, Wadih

2017-01-01

Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a non-proteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short time frame. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. PMID:28428279

Human hyoid bones from the middle Pleistocene site of the Sima de los Huesos (Sierra de Atapuerca, Spain).

PubMed

Martínez, I; Arsuaga, J L; Quam, R; Carretero, J M; Gracia, A; Rodríguez, L

2008-01-01

This study describes and compares two hyoid bones from the middle Pleistocene site of the Sima de los Huesos in the Sierra de Atapuerca (Spain). The Atapuerca SH hyoids are humanlike in both their morphology and dimensions, and they clearly differ from the hyoid bones of chimpanzees and Australopithecus afarensis. Their comparison with the Neandertal specimens Kebara 2 and SDR-034 makes it possible to begin to approach the question of temporal variation and sexual dimorphism in this bone in fossil humans. The results presented here show that the degree of metric and anatomical variation in the fossil sample was similar in magnitude and kind to living humans. Modern hyoid morphology was present by at least 530 kya and appears to represent a shared derived feature of the modern human and Neandertal evolutionary lineages inherited from their last common ancestor.

Three-Dimensional Arrangement of Human Bone Marrow Microvessels Revealed by Immunohistology in Undecalcified Sections

PubMed Central

Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Neff, Andreas; Guthe, Michael; Lobachev, Oleg

2016-01-01

The arrangement of microvessels in human bone marrow is so far unknown. We combined monoclonal antibodies against CD34 and against CD141 to visualise all microvessel endothelia in 21 serial sections of about 1 cm2 size derived from a human iliac crest. The specimen was not decalcified and embedded in Technovit® 9100. In different regions of interest, the microvasculature was reconstructed in three dimensions using automatic methods. The three-dimensional models were subject to a rigid semiautomatic and manual quality control. In iliac crest bone marrow, the adipose tissue harbours irregularly distributed haematopoietic areas. These are fed by networks of large sinuses, which are loosely connected to networks of small capillaries prevailing in areas of pure adipose tissue. Our findings are compatible with the hypothesis that capillaries and sinuses in human iliac crest bone marrow are partially arranged in parallel. PMID:27997569

Generation of clinical grade human bone marrow stromal cells for use in bone regeneration

PubMed Central

Robey, Pamela G.; Kuznetsov, Sergei A.; Ren, Jiaqiang; Klein, Harvey G.; Sabatino, Marianna; Stroncek, David F.

2014-01-01

In current orthopaedic practice, there is a need to increase the ability to reconstruct large segments of bone lost due to trauma, resection of tumors and skeletal deformities, or when normal regenerative processes have failed such as in non-unions and avascular necrosis. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells), when used in conjunction with appropriate carriers, represent a means by which to achieve bone regeneration in such cases. While much has been done at the bench and in pre-clinical studies, moving towards clinical application requires the generation of clinical grade cells. What is described herein is an FDA-approved cell manufacturing procedure for the ex vivo expansion of high quality, biologically active human BMSCs. PMID:25064527

Recombinant human bone morphogenetic protein 2 in augmentation procedures: case reports.

PubMed

Luiz, Jaques; Padovan, Luis Eduardo Marques; Claudino, Marcela

2014-01-01

To successfully rehabilitate edentulous patients using endosseous implants, there must be enough available bone. Several techniques have been proposed for augmentation of sites with insufficient bone volume. Although autogenous bone has long been considered the gold standard for such procedures, the limited availability of graft material and a high morbidity rate are potential disadvantages of this type of graft. An alternative is to use recombinant human bone morphogenetic protein 2 (rhBMP-2), which is able to support bone regeneration in the oral environment. These cases demonstrate the applicability of rhBMP-2 in maxillary sinus elevation and augmentation procedures in the maxilla to enable dental implant placement. The use of rhBMP-2 in alveolar augmentation procedures had several clinical benefits for these patients.

On the rat model of human osteopenias and osteoporoses

NASA Technical Reports Server (NTRS)

Frost, Harold M.; Jee, Webster S. S.

1992-01-01

The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

ADRA2A is involved in neuro-endocrine regulation of bone resorption

PubMed Central

Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

2015-01-01

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. PMID:25818344

Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

PubMed

Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2014-10-01

The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. © 2014 American Society for Bone and Mineral Research.

Comparison of a novel bone-tendon allograft with a human dermis-derived patch for repair of chronic large rotator cuff tears using a canine model.

PubMed

Smith, Matthew J; Cook, James L; Kuroki, Keiichi; Jayabalan, Prakash S; Cook, Cristi R; Pfeiffer, Ferris M; Waters, Nicole P

2012-02-01

This study tested a bone-tendon allograft versus human dermis patch for reconstructing chronic rotator cuff repair by use of a canine model. Mature research dogs (N = 15) were used. Radiopaque wire was placed in the infraspinatus tendon (IST) before its transection. Three weeks later, radiographs showed IST retraction. Each dog then underwent 1 IST treatment: debridement (D), direct repair of IST to bone with a suture bridge and human dermis patch augmentation (GJ), or bone-tendon allograft (BT) reconstruction. Outcome measures included lameness grading, radiographs, and ultrasonographic assessment. Dogs were killed 6 months after surgery and both shoulders assessed biomechanically and histologically. BT dogs were significantly (P = .01) less lame than the other groups. BT dogs had superior bone-tendon, tendon, and tendon-muscle integrity compared with D and GJ dogs. Biomechanical testing showed that the D group had significantly (P = .05) more elongation than the other groups whereas BT had stiffness and elongation characteristics that most closely matched normal controls. Radiographically, D and GJ dogs showed significantly more retraction than BT dogs (P = .003 and P = .045, respectively) Histologically, GJ dogs had lymphoplasmacytic infiltrates, tendon degeneration and hypocellularity, and poor tendon-bone integration. BT dogs showed complete incorporation of allograft bone into host bone, normal bone-tendon junctions, and well-integrated allograft tendon. The bone-tendon allograft technique re-establishes a functional IST bone-tendon-muscle unit and maintains integrity of repair in this model. Clinical trials using this bone-tendon allograft technique are warranted. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Bioreactor Cultivation of Anatomically Shaped Human Bone Grafts

PubMed Central

Temple, Joshua P.; Yeager, Keith; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana; Grayson, Warren L.

2015-01-01

In this chapter, we describe a method for engineering bone grafts in vitro with the specific geometry of the temporomandibular joint (TMJ) condyle. The anatomical geometry of the bone grafts was segmented from computed tomography (CT) scans, converted to G-code, and used to machine decellularized trabecular bone scaffolds into the identical shape of the condyle. These scaffolds were seeded with human bone marrow-derived mesenchymal stem cells (MSCs) using spinner flasks and cultivated for up to 5 weeks in vitro using a custom-designed perfusion bioreactor system. The flow patterns through the complex geometry were modeled using the FloWorks module of SolidWorks to optimize bioreactor design. The perfused scaffolds exhibited significantly higher cellular content, better matrix production, and increased bone mineral deposition relative to non-perfused (static) controls after 5 weeks of in vitro cultivation. This technology is broadly applicable for creating patient-specific bone grafts of varying shapes and sizes. PMID:24014312

Animal Models of Bone Metastasis

PubMed Central

Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

2015-01-01

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

Expression of extracellular calcium (Ca2+o)-sensing receptor in human peripheral blood monocytes

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Olozak, I.; Chattopadhyay, N.; Butters, R. R.; Kifor, O.; Scadden, D. T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor playing key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone turnover and may play a role in the "reversal" phase of skeletal remodeling that follows osteoclastic resorption and precedes osteoblastic bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for such mononuclear cells present locally within the bone marrow microenvironment. Indeed, previous studies by other investigators have shown that raising Ca2+o either in vivo or in vitro stimulated the release of interleukin-6 (IL-6) from human peripheral blood monocytes, suggesting that these cells express a Ca2+o-sensing mechanism. In these earlier studies, however, the use of reverse transcription-polymerase chain reaction (RT-PCR) failed to detect transcripts for the CaR previously cloned from parathyroid and kidney in peripheral blood monocytes. Since we recently found that non-specific esterase-positive, putative monocytes isolated from murine bone marrow express the CaR, we reevaluated the expression of this receptor in human peripheral blood monocytes. Immunocytochemistry, flow cytometry, and Western blot analysis, performed using a polyclonal antiserum specific for the CaR, detected CaR protein in human monocytes. In addition, the use of RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products, identified CaR transcripts in the cells. Therefore, taken together, our data show that human peripheral blood monocytes possess both CaR protein and mRNA very similar if not identical to those expressed in parathyroid and kidney that could mediate the previously described, direct effects of Ca2+o on these cells. Furthermore, since mononuclear cells isolated from bone marrow also express the CaR, the latter might play some role in the "reversal" phase of bone remodeling, sensing local changes in Ca2+o resulting from osteoclastic bone resorption and secreting osteotropic cytokines or performing other Ca2+o-regulated functions that contribute to the control of bone turnover.

Mechanical basis of bone strength: influence of bone material, bone structure and muscle action.

PubMed

Hart, N H; Nimphius, S; Rantalainen, T; Ireland, A; Siafarikas, A; Newton, R U

2017-09-01

This review summarises current understanding of how bone is sculpted through adaptive processes, designed to meet the mechanical challenges it faces in everyday life and athletic pursuits, serving as an update for clinicians, researchers and physical therapists. Bone's ability to resist fracture under the large muscle and locomotory forces it experiences during movement and in falls or collisions is dependent on its established mechanical properties, determined by bone's complex and multidimensional material and structural organisation. At all levels, bone is highly adaptive to habitual loading, regulating its structure according to components of its loading regime and mechanical environment, inclusive of strain magnitude, rate, frequency, distribution and deformation mode. Indeed, the greatest forces habitually applied to bone arise from muscular contractions, and the past two decades have seen substantial advances in our understanding of how these forces shape bone throughout life. Herein, we also highlight the limitations of in vivo methods to assess and understand bone collagen, and bone mineral at the material or tissue level. The inability to easily measure or closely regulate applied strain in humans is identified, limiting the translation of animal studies to human populations, and our exploration of how components of mechanical loading regimes influence mechanoadaptation.

Journey into Bone Models: A Review

PubMed Central

Scheinpflug, Julia; Pfeiffenberger, Moritz; Damerau, Alexandra; Schwarz, Franziska; Textor, Martin; Lang, Annemarie

2018-01-01

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed. In addition, animal models are still regarded as the gold-standard in the context of bone biology and pathology, especially for the development of novel treatment strategies. However, species-specific differences impede the translation of findings from animal models to humans. The current review summarizes and discusses the latest developments in bone tissue engineering and organoid culture including suitable cell sources, extracellular matrices and microfluidic bioreactor systems. With available technology in mind, a best possible bone model will be hypothesized. Furthermore, the future need and application of such a complex model will be discussed. PMID:29748516

Journey into Bone Models: A Review.

PubMed

Scheinpflug, Julia; Pfeiffenberger, Moritz; Damerau, Alexandra; Schwarz, Franziska; Textor, Martin; Lang, Annemarie; Schulze, Frank

2018-05-10

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed. In addition, animal models are still regarded as the gold-standard in the context of bone biology and pathology, especially for the development of novel treatment strategies. However, species-specific differences impede the translation of findings from animal models to humans. The current review summarizes and discusses the latest developments in bone tissue engineering and organoid culture including suitable cell sources, extracellular matrices and microfluidic bioreactor systems. With available technology in mind, a best possible bone model will be hypothesized. Furthermore, the future need and application of such a complex model will be discussed.

Quantitative computed tomography and cranial burr holes: a model to evaluate the quality of cranial reconstruction in humans.

PubMed

Worm, Paulo Valdeci; Ferreira, Nelson Pires; Ferreira, Marcelo Paglioli; Kraemer, Jorge Luiz; Lenhardt, Rene; Alves, Ronnie Peterson Marcondes; Wunderlich, Ricardo Castilho; Collares, Marcus Vinicius Martins

2012-05-01

Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.

Pullout strength of bone-patellar tendon-bone allograft bone plugs: a comparison of cadaver tibia and rigid polyurethane foam.

PubMed

Barber, F Alan

2013-09-01

To compare the load-to-failure pullout strength of bone-patellar tendon-bone (BPTB) allografts in human cadaver tibias and rigid polyurethane foam blocks. Twenty BPTB allografts were trimmed creating 25 mm × 10 mm × 10 mm tibial plugs. Ten-millimeter tunnels were drilled in 10 human cadaver tibias and 10 rigid polyurethane foam blocks. The BPTB anterior cruciate ligament allografts were inserted into these tunnels and secured with metal interference screws, with placement of 10 of each type in each material. After preloading (10 N), cyclic loading (500 cycles, 10 to 150 N at 200 mm/min) and load-to-failure testing (200 mm/min) were performed. The endpoints were ultimate failure load, cyclic loading elongation, and failure mode. No difference in ultimate failure load existed between grafts inserted into rigid polyurethane foam blocks (705 N) and those in cadaver tibias (669 N) (P = .69). The mean rigid polyurethane foam block elongation (0.211 mm) was less than that in tibial bone (0.470 mm) (P = .038), with a smaller standard deviation (0.07 mm for foam) than tibial bone (0.34 mm). All BPTB grafts successfully completed 500 cycles. The rigid polyurethane foam block showed less variation in test results than human cadaver tibias. Rigid polyurethane foam blocks provide an acceptable substitute for human cadaver bone tibia for biomechanical testing of BPTB allografts and offer near-equivalent results. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Blockade of CD26 signaling inhibits human osteoclast development.

PubMed

Nishida, Hiroko; Suzuki, Hiroshi; Madokoro, Hiroko; Hayashi, Mutsumi; Morimoto, Chikao; Sakamoto, Michiie; Yamada, Taketo

2014-11-01

Bone remodeling is maintained by the delicate balance between osteoblasts (OBs) and osteoclasts (OCs). However, the role of CD26 in regulating bone remodeling has not yet been characterized. We herein show that CD26 is preferentially expressed on normal human OCs and is intensely expressed on activated human OCs in osteolytic bone alterations. Macrophage-colony stimulating factor (M-CSF) and soluble receptor activator of NF-κB ligand (sRANKL) induced human OC differentiation, in association with CD26 expression on monocyte-macrophage lineage cells. CD26 expression was accompanied by increased phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which is crucial for early human OC differentiation. The humanized anti-CD26 monoclonal antibody, huCD26mAb, impaired the formation and function of tartrate-resistant acid phosphatase (TRAP)/CD26 positive multi-nucleated (nuclei > 3) OCs with maturation in the manner of dose-dependency. It was revealed that huCD26mAb inhibits early OC differentiation via the inactivation of MKK3/6, p38 MAPK and subsequent dephosphorylation of microphthalmia-associated transcription factor (mi/Mitf). These inhibitions occur immediately after RANKL binds to RANK on the human OC precursor cells and were demonstrated using the OC functional assays. huCD26mAb subsequently impaired OC maturation and bone resorption by suppressing the expression of TRAP and OC fusion proteins. In addition, p38 MAPK inhibitor also strongly inhibited OC formation and function. Our results suggest that the blockade of CD26 signaling impairs the development of human functional OCs by inhibiting p38 MAPK-mi/Mitf phosphorylation pathway and that targeting human OCs with huCD26mAb may have therapeutic potential for the treatment of osteolytic lesions following metastasis to alleviate bone destruction and reduce total skeletal-related events (SREs). © 2014 American Society for Bone and Mineral Research.

Three-dimensional co-culture of human hepatocytes and mesenchymal stem cells: improved functionality in long-term bioreactor cultures.

PubMed

Rebelo, Sofia P; Costa, Rita; Silva, Marta M; Marcelino, Paulo; Brito, Catarina; Alves, Paula M

2017-07-01

The development of human cell models that can efficiently restore hepatic functionality and cope with the reproducibility and scalability required for preclinical development poses a significant effort in tissue engineering and biotechnology. Primary cultures of human hepatocytes (HHs), the preferred model for in vitro toxicity testing, dedifferentiate and have short-term viability in two-dimensional (2D) cultures. In this study, hepatocytes isolated from human liver tissue were co-cultured with human bone marrow mesenchymal stem cells (BM-MSCs) as spheroids in automated, computer-controlled, stirred-tank bioreactors with perfusion operation mode. A dual-step inoculation strategy was used, resulting in an inner core of parenchymal liver tissue with an outer layer of stromal cells. Hepatocyte polarization and morphology as well as the mesenchymal phenotype of BM-MSCs were maintained throughout the culture period and the crosstalk between the two cell types was depicted. The viability, compact morphology and phenotypic stability of hepatocytes were enhanced in co-cultures in comparison to monocultures. Gene expression of phase I and II enzymes was higher and CYP3A4 and CYP1A2 activity was inducible until week 2 of culture, being applicable for repeated-dose toxicity testing. Moreover, the excretory activity was maintained in co-cultures and the biosynthetic hepatocellular functions (albumin and urea secretion) were not affected by the presence of BM-MSCs. This strategy might be extended to other hepatic cell sources and the characterization performed brings knowledge on the interplay between the two cell types, which may be relevant for therapeutic applications. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

PubMed

Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

2017-02-14

Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Comparison of fluoride concentrations in human, dog, fox and raccoon dog bones from northwestern Poland].

PubMed

Palczewska-Komsa, Mirona

2015-01-01

Since the beginning of the XXth there has been a constant increase in fluoride (F-) emissions into the environment, mainly due to the development of industry, the fluoridation of drinking water, and the widespread use of toothpaste containing fluoride. All these factors have resulted in an intensive accumulation of F- in the bodies of vertebrates, mainly in their bones. It is therefore reasonable to estimate the F- concentration in humans and other long-lived mammals. Accordingly, ecotoxicologists worldwide have looked for mammalian species that may serve as good bioindicators of environmental fluoride pollution. In contrast to ungulates, long-lived domestic mammals and wild carnivores have rarely been used for this purpose (including the dog, fox and raccoon dog). The main aims of this study were to: 1) investigate F- concentrations in bones obtained from humans, dog, fox and raccoon dog from northwestern Poland, 2) perform intra- and inter-specific comparisons of F- concentrations in the studied mammalian bones against the background of environmental and living conditions, 3) examine the relationship between concentrations of F- in bones and the age or age category of the studied mammals. The study material comprised bones of the hip joint obtained from 36 patients who underwent hip replacement in Szczecin, 43 dogs from Szczecin veterinary clinics, 32 foxes and 18 raccoon dogs provided by hunters, with the whole test material consisting of 129 samples. The indications of F- (using potentiometry with Thermo Orion ion-selective electrodes) were performed in triplicate. The F- concentration was expressed on a dry weight basis. Interspecific analysis showed that the largest number of differences in the concentrations of F- were between the fox and raccoon, and then between the dog and fox, and then between the dog and the wild canids (foxes and raccoon dogs together). Close statistically significant differences were also found between the samples from humans and the fox, and also between human and dog bones. There were no statistically significant differences in the concentrations of F- between humans and raccoons, humans and canids (dog, fox, raccoon dog together), and between dogs and raccoon dogs. Domesticated and wild canids are good bioindicators of environmental levels of fluoride, because they reflect the concentration of fluoride in bones observed in humans who lived in a similar area.

Percutaneously drilling through femoral head and neck fenestration combining with compacted autograft for early femoral head necrosis: A retrospective study.

PubMed

Li, Donghai; Xie, Xiaowei; Kang, Pengde; Shen, Bin; Pei, Fuxing; Wang, Changde

2017-11-01

The purpose of this study was to evaluate the clinical results, survivorship and quick rehabilitation effects of modified surgery of percutaneously drilling and decompression through femoral head and neck fenestration combined with compacted autograft for early femoral head necrosis. We conducted a retrospective cohort study with 83 hips performed percutaneous decompression through femoral head and neck fenestration (Modified group) combined with autogenous bone grafting for early ONFH. For comparison, another 90 hips treated with conventional core decompression with bone grafting (Control group). Median follow-up was 36 months (32-44 months). The length of incision, blood loss in operation, incision drainage, operation time and hospital stays in Modified group had better results than those in control group (P < 0.001). There were four cases in Modified group and five cases in control group had complications (P = 0.9). The VAS score and range of hip motion were better in Modified group during hospital stays summarily (P < 0.05). The average Harris score in modified group was higher than the control group at the first month (P = 0.005), while at other time of follow-up the two groups were with similar Harris scores (P > 0.05). There were 22 hips progressed to stage III in Modified group, while 23 hips progressed to stage III in control group (P = 0.89). The clinical success rate in Modified group were 86.7%, compared with that in control group (87.8%) ( P= 0.84). Percutaneous drilling and decompression through femoral head and neck fenestration combined with compacted autograft we reported showed an good surgical effect with a quick rehabilitation and had similar short-term effects compared with the conventional core decompression in treatment of early ONFH. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Comminuted olecranon fracture fixation with pre-contoured plate: Comparison of composite and cadaver bones

PubMed Central

Hamilton Jr, David A; Reilly, Danielle; Wipf, Felix; Kamineni, Srinath

2015-01-01

AIM: To determine whether use of a precontoured olecranon plate provides adequate fixation to withstand supraphysiologic force in a comminuted olecranon fracture model. METHODS: Five samples of fourth generation composite bones and five samples of fresh frozen human cadaveric left ulnae were utilized for this study. The cadaveric specimens underwent dual-energy X-ray absorptiometry (DEXA) scanning to quantify the bone quality. The composite and cadaveric bones were prepared by creating a comminuted olecranon fracture and fixed with a pre-contoured olecranon plate with locking screws. Construct stiffness and failure load were measured by subjecting specimens to cantilever bending moments until failure. Fracture site motion was measured with differential variable resistance transducer spanning the fracture. Statistical analysis was performed with two-tailed Mann-Whitney-U test with Monte Carlo Exact test. RESULTS: There was a significant difference in fixation stiffness and strength between the composite bones and human cadaver bones. Failure modes differed in cadaveric and composite specimens. The load to failure for the composite bones (n = 5) and human cadaver bones (n = 5) specimens were 10.67 nm (range 9.40-11.91 nm) and 13.05 nm (range 12.59-15.38 nm) respectively. This difference was statistically significant (P ˂ 0.007, 97% power). Median stiffness for composite bones and human cadaver bones specimens were 5.69 nm/mm (range 4.69-6.80 nm/mm) and 7.55 nm/mm (range 6.31-7.72 nm/mm). There was a significant difference for stiffness (P ˂ 0.033, 79% power) between composite bones and cadaveric bones. No correlation was found between the DEXA results and stiffness. All cadaveric specimens withstood the physiologic load anticipated postoperatively. Catastrophic failure occurred in all composite specimens. All failures resulted from composite bone failure at the distal screw site and not hardware failure. There were no catastrophic fracture failures in the cadaveric specimens. Failure of 4/5 cadaveric specimens was defined when a fracture gap of 2 mm was observed, but 1/5 cadaveric specimens failed due to a failure of the triceps mechanism. All failures occurred at forces greater than that expected in postoperative period prior to healing. CONCLUSION: The pre-contoured olecranon plate provides adequate fixation to withstand physiologic force in a composite bone and cadaveric comminuted olecranon fracture model. PMID:26495247

Bone sialoprotein and its transcriptional regulatory mechanism.

PubMed

Ogata, Y

2008-04-01

Bone sialoprotein is a mineralized tissue-specific noncollagenous protein that is glycosylated, phosphorylated and sulfated. The temporo-spatial deposition of bone sialoprotein into the extracellular matrix of bone, and the ability of bone sialoprotein to nucleate hydroxyapatite crystal formation, indicates a potential role for bone sialoprotein in the initial mineralization of bone, dentin and cementum. Bone sialoprotein is also expressed in breast, lung, thyroid and prostate cancers. We used osteoblast-like cells (rat osteosarcoma cell lines ROS17/2.8 and UMR106, rat stromal bone marrow RBMC-D8 cells and human osteosarcoma Saos2 cells), and breast and prostate cancer cells to investigate the transcriptional regulation of bone sialoprotein. To determine the molecular basis of the transcriptional regulation of the bone sialoprotein gene, we conducted northern hybridization, transient transfection analyses with chimeric constructs of the bone sialoprotein gene promoter linked to a luciferase reporter gene and gel mobility shift assays. Bone sialoprotein transcription is regulated by hormones, growth factors and cytokines through tyrosine kinase, mitogen-activated protein kinase and cAMP-dependent pathways. Microcalcifications are often associated with human mammary lesions, particularly with breast carcinomas. Expression of bone sialoprotein by cancer cells could play a major role in the mineral deposition and in preferred bone homing of breast cancer cells. Bone sialoprotein protects cells from complement-mediated cellular lysis, activates matrix metalloproteinase 2 and has an angiogenic capacity. Therefore, regulation of the bone sialoprotein gene is potentially important in the differentiation of osteoblasts, bone matrix mineralization and tumor metastasis. This review highlights the function and transcriptional regulation of bone sialoprotein.

[Mechanism of "crescent sign" formation in avascular necrosis of femoral head].

PubMed

Zhang, Nianfei; Qi, Shengwen; Chai, Jianfeng

2008-03-01

To investigate corresponding relation between structure change of the femoral head with "crescent sign" and stress exerted on the avascular necrosis of femoral head, to explore the mechanism of the "crescent sign" formation. From March 1998 to April 2003, the femoral heads of 18 hips in 16 cases having osteonecrosis and "crescent sign" in X-ray film before total hip arthroplasty, were collected. General and coronal section plane morphology of the femoral heads were observed. The principle of effective stress and stress concentration theory were used to explain the phenomena and structure changes in osteonecrosis of the femoral head. Cancellous bone existed as a three-dimensional, interconnected network of trabeculae rods and plates, with 50%-90% of porosity and 20-30 mmHg bone marrow pressure. According to the definition of porous media, bones especially cancellous bone was a kind of solid and liquid two phases porous media. Cross-sectional structure changes in the junction between subchondral plate and cancellous were the place where stress concentrated. The principle of effective stress and stress concentration theory could explain the phenomena and their relationship that occurred in avascular necrosis of the femoral head. The "crescent sign" starts in an area of very focal resorption in the subchondral plate laterally and peripherally. The focal resorption in the subchondral plate breaks the continuity of subchondral plate and causes stress concentration in the resorption region. The concentrated stress accumulates in the junction between subchondral plate and unrepaired necrotic cancellous bone brings on the fracture right below the subchondral plate. The focal resorption of the subchondral plate also provides a pathway for the pore water in the unrepaired necrotic bone skeleton to outflow, therefore cause effective stress increase and unrepaired necrotic bone skeleton be compacted by increased effective stress applied on unrepaired necrotic cancellous bone skeleton, and results in the volume decrease of unrepaired necrotic cancellous bone and the formation of cavum below the subchondral plate. The cavum shows "crescent sign" in the X-ray film.

Osteoporosis imaging: effects of bone preservation on MDCT-based trabecular bone microstructure parameters and finite element models.

PubMed

Baum, Thomas; Grande Garcia, Eduardo; Burgkart, Rainer; Gordijenko, Olga; Liebl, Hans; Jungmann, Pia M; Gruber, Michael; Zahel, Tina; Rummeny, Ernst J; Waldt, Simone; Bauer, Jan S

2015-06-26

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength due to a reduction of bone mass and deterioration of bone microstructure predisposing an individual to an increased risk of fracture. Trabecular bone microstructure analysis and finite element models (FEM) have shown to improve the prediction of bone strength beyond bone mineral density (BMD) measurements. These computational methods have been developed and validated in specimens preserved in formalin solution or by freezing. However, little is known about the effects of preservation on trabecular bone microstructure and FEM. The purpose of this observational study was to investigate the effects of preservation on trabecular bone microstructure and FEM in human vertebrae. Four thoracic vertebrae were harvested from each of three fresh human cadavers (n=12). Multi-detector computed tomography (MDCT) images were obtained at baseline, 3 and 6 month follow-up. In the intervals between MDCT imaging, two vertebrae from each donor were formalin-fixed and frozen, respectively. BMD, trabecular bone microstructure parameters (histomorphometry and fractal dimension), and FEM-based apparent compressive modulus (ACM) were determined in the MDCT images and validated by mechanical testing to failure of the vertebrae after 6 months. Changes of BMD, trabecular bone microstructure parameters, and FEM-based ACM in formalin-fixed and frozen vertebrae over 6 months ranged between 1.0-5.6% and 1.3-6.1%, respectively, and were not statistically significant (p>0.05). BMD, trabecular bone microstructure parameters, and FEM-based ACM as assessed at baseline, 3 and 6 month follow-up correlated significantly with mechanically determined failure load (r=0.89-0.99; p<0.05). The correlation coefficients r were not significantly different for the two preservation methods (p>0.05). Formalin fixation and freezing up to six months showed no significant effects on trabecular bone microstructure and FEM-based ACM in human vertebrae and may both be used in corresponding in-vitro experiments in the context of osteoporosis.

Histomorphometric, fractal and lacunarity comparative analysis of sheep (Ovis aries), goat (Capra hircus) and roe deer (Capreolus capreolus) compact bone samples.

PubMed

Gudea, A I; Stefan, A C

2013-08-01

Quantitative and qualitative studies dealing with histomorphometry of the bone tissue play a new role in modern legal medicine/forensic medicine and archaeozoology nowadays. This study deals with the differences found in case of humerus and metapodial bones of recent sheep (Ovis aries), goat (Capra hircus) and roedeer (Capreolus capreolus) specimens, both from a qualitative point of view, but mainly from a quantitative perspective. A novel perspective given by the fractal analysis performed on the digital histological images is approached. This study shows that the qualitative assessment may not be a reliable one due to the close resemblance of the structures. From the quantitative perspective (several measurements performed on osteonal units and statistical processing of data),some of the elements measured show significant differences among 3 species(the primary osteonal diameter, etc.). The fractal analysis and the lacunarity of the images show a great deal of potential, proving that this type of analysis can be of great help in the separation of the material from this perspective.

Os incae: variation in frequency in major human population groups

PubMed Central

HANIHARA, TSUNEHIKO; ISHIDA, HAJIME

2001-01-01

The variation in frequency of the Inca bone was examined in major human populations around the world. The New World populations have generally high frequencies of the Inca bone, whereas lower frequencies occur in northeast Asians and Australians. Tibetan/Nepalese and Assam/Sikkim populations in northeast India have more Inca bones than do neighbouring populations. Among modern populations originally derived from eastern Asian population stock, the frequencies are highest in some of the marginal isolated groups. In Central and West Asia as well as in Europe, frequency of the Inca bone is relatively low. The incidence of the complete Inca bone is, moreover, very low in the western hemisphere of the Old World except for Subsaharan Africa. Subsaharan Africans show as a whole a second peak in the occurrence of the Inca bone. Geographical and ethnographical patterns of the frequency variation of the Inca bone found in this study indicate that the possible genetic background for the occurrence of this bone cannot be completely excluded. Relatively high frequencies of the Inca bone in Subsaharan Africans indicate that this trait is not a uniquely eastern Asian regional character. PMID:11273039

The role of hesperetin on osteogenesis of human mesenchymal stem cells and its function in bone regeneration.

PubMed

Xue, Deting; Chen, Erman; Zhang, Wei; Gao, Xiang; Wang, Shengdong; Zheng, Qiang; Pan, Zhijun; Li, Hang; Liu, Ling

2017-03-28

Hesperetin has been suggested to be involved in bone strength. We aimed to investigate the effects of hesperetin on the osteogenic differentiation of human mesenchymal stem cells and its related mechanisms. We showed that hesperetin promoted osteogenic differentiation of human mesenchymal stem cells in vitro. It potentially exerts its effects via the ERK and Smad signaling pathways. Using a rat osteotomy model, we showed that human mesenchymal stem cells combined with a hesperetin/gelatin sponge scaffold resulted in accelerated fracture healing in vivo. Due to the low cost of hesperetin, it could be used as a growth factor for bone tissue engineering or surgical fracture treatment.

Compact Eucapnic Voluntary Hyperpnoea Apparatus for Exercise-Induced Respiratory Disease Detection

PubMed Central

Wang, Lulu; Al-Jumaily, Ahmed

2017-01-01

Eucapnic voluntary hyperpnoea (EVH) challenge provides objective criteria for exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB), and it was recommended to justify the use of inhaled β2-agonists by athletes for the Olympics. This paper presents the development of a compact and easy-to-use EVH apparatus for assessing EIB in human subjects. The compact apparatus has been validated on human subjects and the results have been compared to the conventional EVH system. Twenty-two swimmers, including eleven healthy subjects and eleven subjects who had been physician-diagnosed with asthma, were recruited from sport and recreation centers throughout Auckland, New Zealand. Each subject performed two EVH challenge tests using the proposed breathing apparatus and the conventional Phillips EVH apparatus on separate days, respectively. Forced expiratory volume in one second (FEV1) was measured before and after the challenges. A reduction in FEV1 of 10% or more was considered positive. Of the eleven subjects who were previously diagnosed with asthma, EIB was present in all subjects (100%) in the compact EVH group, while it was presented in ten subjects (90.91%) in the conventional EVH challenge group. Of the eleven healthy subjects, EIB was present in one subject (4.55%) in the compact EVH group, while it was not present in the conventional EVH group. Experimental results showed that the compact EVH system has potential to become an alternative tool for EIB detection. PMID:28509868

Nanocrystalline hydroxyapatite bone substitute leads to sufficient bone tissue formation already after 3 months: histological and histomorphometrical analysis 3 and 6 months following human sinus cavity augmentation.

PubMed

Ghanaati, Shahram; Barbeck, Mike; Willershausen, Ines; Thimm, Benjamin; Stuebinger, Stefan; Korzinskas, Tadas; Obreja, Karina; Landes, Constantin; Kirkpatrick, Charles J; Sader, Robert A

2013-12-01

In this study the de novo bone formation capacity of a nanocrystalline hydroxyapatite bone substitute was assessed 3 and 6 months after its insertion into the human sinus cavity. Sinus cavity augmentation was performed in a total of 14 patients (n = 7 implantation after 3 months; n = 7 implantation after 6 months) with severely atrophic maxillary bone. The specimens obtained after 3 and 6 months were analyzed histologically and histomorphometrically with special focus on bone metabolism within the residual bone and the augmented region. This study revealed that bone tissue formation started from the bone-biomaterial-interface and was directed into the most cranial parts of the augmented region. There was no statistically significant difference in new bone formation after 3 and 6 months (24.89 ± 10.22% vs 31.29 ± 2.29%), respectively. Within the limits of the present study and according to previously published data, implant insertion in regions augmented with this bone substitute material could be considered already after 3 months. Further clinical studies with bone substitute materials are necessary to validate these findings. © 2012 Wiley Periodicals, Inc.

Accuracy and reproducibility of bending stiffness measurements by mechanical response tissue analysis in artificial human ulnas.

PubMed

Arnold, Patricia A; Ellerbrock, Emily R; Bowman, Lyn; Loucks, Anne B

2014-11-07

Osteoporosis is characterized by reduced bone strength, but no FDA-approved medical device measures bone strength. Bone strength is strongly associated with bone stiffness, but no FDA-approved medical device measures bone stiffness either. Mechanical Response Tissue Analysis (MRTA) is a non-significant risk, non-invasive, radiation-free, vibration analysis technique for making immediate, direct functional measurements of the bending stiffness of long bones in humans in vivo. MRTA has been used for research purposes for more than 20 years, but little has been published about its accuracy. To begin to investigate its accuracy, we compared MRTA measurements of bending stiffness in 39 artificial human ulna bones to measurements made by Quasistatic Mechanical Testing (QMT). In the process, we also quantified the reproducibility (i.e., precision and repeatability) of both methods. MRTA precision (1.0±1.0%) and repeatability (3.1 ± 3.1%) were not as high as those of QMT (0.2 ± 0.2% and 1.3+1.7%, respectively; both p<10(-4)). The relationship between MRTA and QMT measurements of ulna bending stiffness was indistinguishable from the identity line (p=0.44) and paired measurements by the two methods agreed within a 95% confidence interval of ± 5%. If such accuracy can be achieved on real human ulnas in situ, and if the ulna is representative of the appendicular skeleton, MRTA may prove clinically useful. Copyright © 2014 Elsevier Ltd. All rights reserved.

DNA and bone structure preservation in medieval human skeletons.

PubMed

Coulson-Thomas, Yvette M; Norton, Andrew L; Coulson-Thomas, Vivien J; Florencio-Silva, Rinaldo; Ali, Nadir; Elmrghni, Samir; Gil, Cristiane D; Sasso, Gisela R S; Dixon, Ronald A; Nader, Helena B

2015-06-01

Morphological and ultrastructural data from archaeological human bones are scarce, particularly data that have been correlated with information on the preservation of molecules such as DNA. Here we examine the bone structure of macroscopically well-preserved medieval human skeletons by transmission electron microscopy and immunohistochemistry, and the quantity and quality of DNA extracted from these skeletons. DNA technology has been increasingly used for analyzing physical evidence in archaeological forensics; however, the isolation of ancient DNA is difficult since it is highly degraded, extraction yields are low and the co-extraction of PCR inhibitors is a problem. We adapted and optimised a method that is frequently used for isolating DNA from modern samples, Chelex(®) 100 (Bio-Rad) extraction, for isolating DNA from archaeological human bones and teeth. The isolated DNA was analysed by real-time PCR using primers targeting the sex determining region on the Y chromosome (SRY) and STR typing using the AmpFlSTR(®) Identifiler PCR Amplification kit. Our results clearly show the preservation of bone matrix in medieval bones and the presence of intact osteocytes with well preserved encapsulated nuclei. In addition, we show how effective Chelex(®) 100 is for isolating ancient DNA from archaeological bones and teeth. This optimised method is suitable for STR typing using kits aimed specifically at degraded and difficult DNA templates since amplicons of up to 250bp were successfully amplified. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of in vitro biocompatibility of NanoBone(®) and BioOss(®) for human osteoblasts.

PubMed

Liu, Qin; Douglas, Timothy; Zamponi, Christiane; Becker, Stephan T; Sherry, Eugene; Sivananthan, Sureshan; Warnke, Frauke; Wiltfang, Jörg; Warnke, Patrick H

2011-11-01

Scaffolds for bone tissue engineering seeded with the patient's own cells might be used as a preferable method to repair bone defects in the future. With the emerging new technologies of nanostructure design, new synthetic biomaterials are appearing on the market. Such scaffolds must be tested in vitro for their biocompatibility before clinical application. However, the choice between a natural or a synthetic biomaterial might be challenging for the doctor and the patient. In this study, we compared the biocompatibility of a synthetic bone substitute, NanoBone(®) , to the widely used natural bovine bone replacement material BioOss(®) . The in vitro behaviour of human osteoblasts on both materials was investigated. Cell performance was determined using scanning electron microscopy (SEM), cell vitality staining and four biocompatibility tests (LDH, MTT, WST, BrdU). We found that both materials showed low cytotoxicity and good biocompatibility. The MTT proliferation test was superior for Nanobone(®) . Both scaffolds caused only little damage to human osteoblasts and justify their clinical application. However, NanoBone(®) was able to support and promote proliferation of human osteoblasts slightly better than BioOss(®) in our chosen test set-up. The results may guide doctors and patients when being challenged with the choice between a natural or a synthetic biomaterial. Further experiments are necessary to determine the comparison of biocompatibility in vivo. © 2011 John Wiley & Sons A/S.

Fracture resistance and reinforcement of immature roots with gutta percha, mineral trioxide aggregate and calcium phosphate bone cement: a standardized in vitro model.

PubMed

Cauwels, Rita G E C; Pieters, Ilse Y; Martens, Luc C; Verbeeck, Ronald M H

2010-04-01

Endodontic treatment of immature teeth is often complicated because of flaring root canals and open apices for which apexification is needed. Long-term prognosis for these teeth is surprisingly low because of cervical root fractures occurring after an impact of weak forces. In this study, an experimental model was developed to determine the fracture resistance of immature teeth and to test the hypothesis that endodontic materials succeed in reinforcing them. Compact and hollow bone cylinders from bovine femurs were used as standardized samples. In order to evaluate the experimental model, fracture resistance in both groups was evaluated by determining the ultimate force to fracture (UFF) under diametral tensile stress. Analysis of variance (ANOVA) revealed a statistically significant difference between the mean values of UFF for both groups, independently of the sampling location or subject. In a following setting, the hypothesis that obturation with gutta percha (GP), mineral trioxide aggregate (MTA), or calcium phosphate bone cement (CPBC) reinforces the hollow bone samples was investigated. Obturation resulted in a significant reinforcement for all materials, but the degree of reinforcement depended on the material. The experimental model appeared to be suitable for in vitro investigation of reinforcement and fracture resistance in a standardized way.

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

PubMed

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Human regulatory T cells do not suppress the antitumor immunity in the bone marrow: a role for bone marrow stromal cells in neutralizing regulatory T cells.

PubMed

Guichelaar, Teun; Emmelot, Maarten E; Rozemuller, Henk; Martini, Bianka; Groen, Richard W J; Storm, Gert; Lokhorst, Henk M; Martens, Anton C; Mutis, Tuna

2013-03-15

Regulatory T cells (Tregs) are potent tools to prevent graft-versus-host disease (GVHD) induced after allogeneic stem cell transplantation or donor lymphocyte infusions. Toward clinical application of Tregs for GVHD treatment, we investigated the impact of Tregs on the therapeutic graft-versus-tumor (GVT) effect against human multiple myeloma tumors with various immunogenicities, progression rates, and localizations in a humanized murine model. Immunodeficient Rag2(-/-)γc(-/-) mice, bearing various human multiple myeloma tumors, were treated with human peripheral blood mononuclear cell (PBMC) alone or together with autologous ex vivo cultured Tregs. Mice were analyzed for the in vivo engraftment, homing of T-cell subsets, development of GVHD and GVT. In additional in vitro assays, Tregs that were cultured together with bone marrow stromal cells were analyzed for phenotype and functions. Treatment with PBMC alone induced variable degrees of antitumor response, depending on the immunogenicity and the growth rate of the tumor. Coinfusion of Tregs did not impair the antitumor response against tumors residing within the bone marrow, irrespective of their immunogenicity or growth rates. In contrast, Tregs readily inhibited the antitumor effect against tumors growing outside the bone marrow. Exploring this remarkable phenomenon, we discovered that bone marrow stroma neutralizes the suppressive activity of Tregs in part via production of interleukin (IL)-1β/IL-6. We furthermore found in vitro and in vivo evidence of conversion of Tregs into IL-17-producing T cells in the bone marrow environment. These results provide new insights into the Treg immunobiology and indicate the conditional benefits of future Treg-based therapies.

Regional Variation of Bone Tissue Properties at the Human Mandibular Condyle

PubMed Central

Kim, Do-Gyoon; Jeong, Yong-Hoon; Kosel, Erin; Agnew, Amanda M.; McComb, David W.; Bodnyk, Kyle; Hart, Richard T.; Kim, Min Kyung; Han, Sang Yeun; Johnston, William M.

2015-01-01

The temporomandibular joint (TMJ) bears different types of static and dynamic loading during occlusion and mastication. As such, characteristics of mandibular condylar bone tissue play an important role in determining the mechanical stability of the TMJ under the macro-level loading. Thus, the objective of this study was to examine regional variation of the elastic, plastic, and viscoelastic mechanical properties of human mandibular condylar bone tissue using nanoindentation. Cortical and trabecular bone were dissected from mandibular condyles of human cadavers (9 males, 54 to 96 years). These specimens were scanned using microcomputed tomography to obtain bone tissue mineral distribution. Then, nanoindentation was conducted on the surface of the same specimens in hydration. Plastic hardness (H) at a peak load, viscoelastic creep (Creep/Pmax), viscosity (η), and tangent delta (tan δ) during a 30 second hold period, and elastic modulus (E) during unloading were obtained by a cycle of indentation at the same site of bone tissue. The tissue mineral and nanoindentation parameters were analyzed for the periosteal and endosteal cortex, and trabecular bone regions of the mandibular condyle. The more mineralized periosteal cortex had higher mean values of elastic modulus, plastic hardness, and viscosity but lower viscoelastic creep and tan δ than the less mineralized trabecular bone of the mandibular condyle. These characteristics of bone tissue suggest that the periosteal cortex tissue may have more effective properties to resist elastic, plastic, and viscoelastic deformation under static loading, and the trabecular bone tissue to absorb and dissipate time-dependent viscoelastic loading energy at the TMJ during static occlusion and dynamic mastication. PMID:25913634

A Method to Represent Heterogeneous Materials for Rapid Prototyping: The Matryoshka Approach.

PubMed

Lei, Shuangyan; Frank, Matthew C; Anderson, Donald D; Brown, Thomas D

The purpose of this paper is to present a new method for representing heterogeneous materials using nested STL shells, based, in particular, on the density distributions of human bones. Nested STL shells, called Matryoshka models, are described, based on their namesake Russian nesting dolls. In this approach, polygonal models, such as STL shells, are "stacked" inside one another to represent different material regions. The Matryoshka model addresses the challenge of representing different densities and different types of bone when reverse engineering from medical images. The Matryoshka model is generated via an iterative process of thresholding the Hounsfield Unit (HU) data using computed tomography (CT), thereby delineating regions of progressively increasing bone density. These nested shells can represent regions starting with the medullary (bone marrow) canal, up through and including the outer surface of the bone. The Matryoshka approach introduced can be used to generate accurate models of heterogeneous materials in an automated fashion, avoiding the challenge of hand-creating an assembly model for input to multi-material additive or subtractive manufacturing. This paper presents a new method for describing heterogeneous materials: in this case, the density distribution in a human bone. The authors show how the Matryoshka model can be used to plan harvesting locations for creating custom rapid allograft bone implants from donor bone. An implementation of a proposed harvesting method is demonstrated, followed by a case study using subtractive rapid prototyping to harvest a bone implant from a human tibia surrogate.

Targeting the LRP5 pathway improves bone properties in a mouse model of Osteogenesis Imperfecta

PubMed Central

Jacobsen, Christina M.; Barber, Lauren A.; Ayturk, Ugur M.; Roberts, Heather J.; Deal, Lauren E.; Schwartz, Marissa A.; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G.; Warman, Matthew L.

2014-01-01

The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5p.A214V) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis Imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5+/p.A214V mice to Col1a2+/p.G610C mice, which model human type IV OI. We found that Col1a2+/p.G610C;Lrp5+/p.A214V offspring had significantly increased bone mass and strength compared to Col1a2+/p.G610C;Lrp5+/+ littermates. The improved bone properties were not due to altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2+/p.G610C mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody treated mice had significantly increased bone mass and strength compared to vehicle treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. PMID:24677211

Perivascular Stem Cells: A Prospectively Purified Mesenchymal Stem Cell Population for Bone Tissue Engineering

PubMed Central

James, Aaron W.; Zara, Janette N.; Zhang, Xinli; Askarinam, Asal; Goyal, Raghav; Chiang, Michael; Yuan, Wei; Chang, Le; Corselli, Mirko; Shen, Jia; Pang, Shen; Stoker, David; Wu, Ben

2012-01-01

Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence-activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient-matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel-like molecule 1 (NELL-1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose-derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell-based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL-1 is a candidate growth factor able to induce human PSC osteogenesis. PMID:23197855

Poly-ε-caprolactone scaffold and reduced in vitro cell culture: beneficial effect on compaction and improved valvular tissue formation.

PubMed

Brugmans, Marieke M C P; Driessen-Mol, Anita; Rubbens, Mirjam P; Cox, Martijn A J; Baaijens, Frank P T

2015-12-01

Tissue-engineered heart valves (TEHVs), based on polyglycolic acid (PGA) scaffolds coated with poly-4-hydroxybutyrate (P4HB), have shown promising in vivo results in terms of tissue formation. However, a major drawback of these TEHVs is compaction and retraction of the leaflets, causing regurgitation. To overcome this problem, the aim of this study was to investigate: (a) the use of the slowly degrading poly-ε-caprolactone (PCL) scaffold for prolonged mechanical integrity; and (b) the use of lower passage cells for enhanced tissue formation. Passage 3, 5 and 7 (P3, P5 and P7) human and ovine vascular-derived cells were seeded onto both PGA-P4HB and PCL scaffold strips. After 4 weeks of culture, compaction, tissue formation, mechanical properties and cell phenotypes were compared. TEHVs were cultured to observe retraction of the leaflets in the native-like geometry. After culture, tissues based on PGA-P4HB scaffold showed 50-60% compaction, while PCL-based tissues showed compaction of 0-10%. Tissue formation, stiffness and strength were increased with decreasing passage number; however, this did not influence compaction. Ovine PCL-based tissues did render less strong tissues compared to PGA-P4HB-based tissues. No differences in cell phenotype between the scaffold materials, species or cell passage numbers were observed. This study shows that PCL scaffolds may serve as alternative scaffold materials for human TEHVs with minimal compaction and without compromising tissue composition and properties, while further optimization of ovine TEHVs is needed. Reducing cell expansion time will result in faster generation of TEHVs, providing more rapid treatment for patients. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of COX-2 (PGE2) and IL-6 on Prostate Cancer Bone Metastases

DTIC Science & Technology

2008-02-02

to stimulate both bone targeting and bone reaction (4). Several factors, such as basic fibroblast growth factor (4), osteocalcin, bone sialoprotein (8...Proc Natl Acad Sci U S A 1990;87:75–9. 8. Huang WC, Xie Z, Konaka H, Sodek J, Zhau HE, Chung LWK. Human osteocalcin and bone sialoprotein medi- ating

The Soy Isoflavones to Reduce Bone Loss (SIRBL) Study: Three Year Effects on pQCT Bone Mineral Density and Strength Measures in Postmenopausal Women

USDA-ARS?s Scientific Manuscript database

Soy isoflavones exert inconsistent bone density preserving effects, but the bone strength preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength ...

Human bone perivascular niche-on-a-chip for studying metastatic colonization.

PubMed

Marturano-Kruik, Alessandro; Nava, Michele Maria; Yeager, Keith; Chramiec, Alan; Hao, Luke; Robinson, Samuel; Guo, Edward; Raimondi, Manuela Teresa; Vunjak-Novakovic, Gordana

2018-02-06

Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone. The model is a functional human triculture with stable vascular networks within a 3D native bone matrix cultured on a microfluidic chip. Providing the niche-on-a-chip with controlled flow velocities, shear stresses, and oxygen gradients, we established a long-lasting, self-assembled vascular network without supplementation of angiogenic factors. We further show that human bone marrow-derived mesenchymal stem cells, which have undergone phenotypical transition toward perivascular cell lineages, support the formation of capillary-like structures lining the vascular lumen. Finally, breast cancer cells exposed to interstitial flow within the bone perivascular niche-on-a-chip persist in a slow-proliferative state associated with increased drug resistance. We propose that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization.

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

NASA Technical Reports Server (NTRS)

Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

1996-01-01

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

Pore cross-section area on predicting elastic properties of trabecular bovine bone for human implants.

PubMed

Maciel, Alfredo; Presbítero, Gerardo; Piña, Cristina; del Pilar Gutiérrez, María; Guzmán, José; Munguía, Nadia

2015-01-01

A clear understanding of the dependence of mechanical properties of bone remains a task not fully achieved. In order to estimate the mechanical properties in bones for implants, pore cross-section area, calcium content, and apparent density were measured in trabecular bone samples for human implants. Samples of fresh and defatted bone tissue, extracted from one year old bovines, were cut in longitudinal and transversal orientation of the trabeculae. Pore cross-section area was measured with an image analyzer. Compression tests were conducted into rectangular prisms. Elastic modulus presents a linear tendency as a function of pore cross-section area, calcium content and apparent density regardless of the trabecular orientation. The best variable to estimate elastic modulus of trabecular bone for implants was pore cross-section area, and affirmations to consider Nukbone process appropriated for marrow extraction in trabecular bone for implantation purposes are proposed, according to bone mechanical properties. Considering stress-strain curves, defatted bone is stiffer than fresh bone. Number of pores against pore cross-section area present an exponential decay, consistent for all the samples. These graphs also are useful to predict elastic properties of trabecular samples of young bovines for implants.

Multi-material 3D Models for Temporal Bone Surgical Simulation.

PubMed

Rose, Austin S; Kimbell, Julia S; Webster, Caroline E; Harrysson, Ola L A; Formeister, Eric J; Buchman, Craig A

2015-07-01

A simulated, multicolor, multi-material temporal bone model can be created using 3-dimensional (3D) printing that will prove both safe and beneficial in training for actual temporal bone surgical cases. As the process of additive manufacturing, or 3D printing, has become more practical and affordable, a number of applications for the technology in the field of Otolaryngology-Head and Neck Surgery have been considered. One area of promise is temporal bone surgical simulation. Three-dimensional representations of human temporal bones were created from temporal bone computed tomography (CT) scans using biomedical image processing software. Multi-material models were then printed and dissected in a temporal bone laboratory by attending and resident otolaryngologists. A 5-point Likert scale was used to grade the models for their anatomical accuracy and suitability as a simulation of cadaveric and operative temporal bone drilling. The models produced for this study demonstrate significant anatomic detail and a likeness to human cadaver specimens for drilling and dissection. Simulated temporal bones created by this process have potential benefit in surgical training, preoperative simulation for challenging otologic cases, and the standardized testing of temporal bone surgical skills. © The Author(s) 2015.

Hypervitaminosis A and bone.

PubMed

Binkley, N; Krueger, D

2000-05-01

Animal, human, and in vitro data all indicate that excess vitamin A stimulates bone resorption and inhibits bone formation. This combination would be expected to produce bone loss and to contribute to osteoporosis development and may occur with relatively low vitamin A intake. It is possible that unappreciated hypervitaminosis A contributes to osteoporosis pathogenesis.

Fifty years of human space travel: implications for bone and calcium research

USDA-ARS?s Scientific Manuscript database

Calcium and bone metabolism remain key concerns for space travelers, and ground-based models of space flight have provided a vast literature to complement the smaller set of reports from flight studies. Increased bone resorption and largely unchanged bone formation result in the loss of calcium and ...

Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation.

PubMed

Minardi, Silvia; Corradetti, Bruna; Taraballi, Francesca; Sandri, Monica; Van Eps, Jeffrey; Cabrera, Fernando J; Weiner, Bradley K; Tampieri, Anna; Tasciotti, Ennio

2015-09-01

Augmentation of regenerative osteogenesis represents a premier clinical need, as hundreds of thousands of patients are left with insufficient healing of bony defects related to a host of insults ranging from congenital abnormalities to traumatic injury to surgically-induced deficits. A synthetic material that closely mimics the composition and structure of the human osteogenic niche represents great potential to successfully address this high demand. In this study, a magnesium-doped hydroxyapatite/type I collagen scaffold was fabricated through a biologically-inspired mineralization process and designed to mimic human trabecular bone. The composition of the scaffold was fully characterized by XRD, FTIR, ICP and TGA, and compared to human bone. Also, the scaffold microstructure was evaluated by SEM, while its nano-structure and nano-mechanical properties were evaluated by AFM. Human bone marrow-derived mesenchymal stem cells were used to test the in vitro capability of the scaffold to promote osteogenic differentiation. The cell/scaffold constructs were cultured up to 7 days and the adhesion, organization and proliferation of the cells were evaluated. The ability of the scaffold to induce osteogenic differentiation of the cells was assessed over 3 weeks and the correlate gene expression for classic genes of osteogenesis was assessed. Finally, when tested in an ectopic model in rabbit, the scaffold produced a large volume of trabecular bone in only two weeks, that subsequently underwent maturation over time as expected, with increased mature cortical bone formation, supporting its ability to promote bone regeneration in clinically-relevant scenarios. Altogether, these results confirm a high level of structural mimicry by the scaffold to the composition and structure of human osteogenic niche that translated to faster and more efficient osteoinduction in vivo--features that suggest such a biomaterial may have great utility in future clinical applications where bone regeneration is required. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Incorporation of Trace Elements in Ancient and Modern Human Bone: An X-Ray Absorption Spectroscopy Study

NASA Astrophysics Data System (ADS)

Pingitore, N. E.; Cruz-Jimenez, G.; Price, T. D.

2001-12-01

X-ray absorption spectroscopy (XAS) affords the opportunity to probe the atomic environment of trace elements in human bone. We are using XAS to investigate the mode(s) of incorporation of Sr, Zn, Pb, and Ba in both modern and ancient (and thus possibly altered) human and animal bone. Because burial and diagenesis may add trace elements to bone, we performed XAS analysis on samples of pristine contemporary and ancient, buried human and animal bone. We assume that deposition of these elements during burial occurs by processes distinct from those in vivo, and this will be reflected in their atomic environments. Archaeologists measure strontium in human and animal bone as a guide to diet. Carnivores show lower Sr/Ca ratios than their herbivore prey due to discrimination against Sr relative to Ca up the food chain. In an initial sample suite no difference was observed between modern and buried bone. Analysis of additional buried samples, using a more sensitive detector, revealed significant differences in the distance to the second and third neighbors of the Sr in some of the buried samples. Distances to the first neighbor, oxygen, were similar in all samples. Zinc is also used in paleo-diet studies. Initial x-ray absorption spectroscopy of a limited suite of bones did not reveal any differences between modern and buried samples. This may reflect the limited number of samples examined or the low levels of Zn in typical aqueous solutions in soils. Signals from barium and lead were too low to record useful XAS spectra. Additional samples will be studied for Zn, Ba, and Pb. We conducted our XAS experiments on beam lines 4-1 and 4-3 at the Stanford Synchrotron Radiation Laboratory. Data were collected in the fluorescence mode, using a Lytle detector and appropriate filter, and a solid state, 13-element Ge-detector.

Effect of space flight on sodium, copper, manganese and magnesium content in the skeletal bones

NASA Technical Reports Server (NTRS)

Prokhonchukov, A. A.; Taitsev, V. P.; Shakhunov, B. A.; Zhizhina, V. A.; Kolesnik, A. G.; Komissarova, N. A.

1979-01-01

Sodium content decreased in the human skeletal bones and rose in the rat bones following space flight. In man copper content rose in the femoral bone and decreased in the vertebral body and the sternum, but was unchanged in the rest of the bones. Magnesium content was decreased in the femoral bone and the sternum, and in the vertebrae, but remained unchanged in the rest of the bones. Possible mechanisms of the changes detected are discussed.

Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women.

PubMed

Pino, Ana María; Ríos, Susana; Astudillo, Pablo; Fernández, Mireya; Figueroa, Paula; Seitz, Germán; Rodríguez, J Pablo

2010-03-01

Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility, and a resulting susceptibility to fractures. Distinctive environmental bone marrow conditions appear to support the development and maintenance of the unbalance between bone resorption and bone formation; these complex bone marrow circumstances would be reflected in the fluid surrounding bone marrow cells. The content of regulatory molecules in the extracellular fluid from the human bone marrow is practically unknown. Since the content of cytokines such as adiponectin, leptin, osteoprogeterin (OPG), soluble receptor activator of nuclear factor kappaB ligand (s-RANKL), tumor necrosis factor alpha, and interleukin 6 (IL-6) may elicit conditions promoting or sustaining osteoporosis, in this work we compared the concentrations of the above-mentioned cytokines and also the level of the soluble receptors for both IL-6 and leptin in the extracellular fluid from the bone marrow of nonosteoporotic and osteoporotic human donors. A supernatant fluid (bone marrow supernatant fluid [BMSF]) was obtained after spinning the aspirated bone marrow samples; donors were classified as nonosteoporotic or osteoporotic after dual-energy X-ray absorptiometry (DXA) measuring. Specific commercially available kits were used for all measurements. The cytokines' concentration in BMSF showed differently among nonosteoporotic and osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic BMSF differentiated by decreased leptin bioavailability, suggesting that insufficient leptin action may distinguish the osteoporotic bone marrow. Copyright 2010 American Society for Bone and Mineral Research.

A methodology for the investigation of toughness and crack propagation in mouse bone.

PubMed

Carriero, Alessandra; Zimmermann, Elizabeth A; Shefelbine, Sandra J; Ritchie, Robert O

2014-11-01

Bone fracture is a health concern for those with aged bone and brittle bone diseases. Mouse bone is widely used as a model of human bone, especially to investigate preclinical treatment strategies. However, little is known about the mechanisms of mouse bone fracture and its similarities and differences from fracture in human bone. In this work we present a methodology to investigate the fracture toughness during crack initiation and crack propagation for mouse bone. Mouse femora were dissected, polished on their periosteal surface, notched on the posterior surface at their mid-diaphysis, and tested in three-point bending under displacement control at a rate of 0.1mm/min using an in situ loading stage within an environmental scanning electron microscope. We obtained high-resolution real-time imaging of the crack initiation and propagation in mouse bone. From the images we can measure the crack extension at each step of the crack growth and calculate the toughness of the bone (in terms of stress intensity factor (K) and work to fracture (Wf)) as a function of stable crack length (Δa), thus generating a resistance curve for the mouse bone. The technique presented here provides insight into the evolution of microdamage and the toughening mechanisms that resist crack propagation, which are essential for preclinical development of treatments to enhance bone quality and combat fracture risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hibernating bears as a model for preventing disuse osteoporosis

USGS Publications Warehouse

Donahue, S.W.; McGee, M.E.; Harvey, K.B.; Vaughan, M.R.; Robbins, C.T.

2006-01-01

The hibernating bear is an excellent model for disuse osteoporosis in humans because it is a naturally occurring large animal model. Furthermore, bears and humans have similar lower limb skeletal morphology, and bears walk plantigrade like humans. Black bears (Ursus americanus) may not develop disuse osteoporosis during long periods of disuse (i.e. hibernation) because they maintain osteoblastic bone formation during hibernation. As a consequence, bone volume, mineral content, porosity, and strength are not adversely affected by annual periods of disuse. In fact, cortical bone bending strength has been shown to increase with age in hibernating black bears without a significant change in porosity. Other animals require remobilization periods 2-3 times longer than the immobilization period to recover the bone lost during disuse. Our findings support the hypothesis that black bears, which hibernate for as long as 5-7 months annually, have evolved biological mechanisms to mitigate the adverse effects of disuse on bone porosity and strength. ?? 2005 Elsevier Ltd. All rights reserved.

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita

2010-03-12

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activitymore » in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.« less

Ptychographic X-ray nanotomography quantifies mineral distributions in human dentine

NASA Astrophysics Data System (ADS)

Zanette, I.; Enders, B.; Dierolf, M.; Thibault, P.; Gradl, R.; Diaz, A.; Guizar-Sicairos, M.; Menzel, A.; Pfeiffer, F.; Zaslansky, P.

2015-03-01

Bones are bio-composites with biologically tunable mechanical properties, where a polymer matrix of nanofibrillar collagen is reinforced by apatite mineral crystals. Some bones, such as antler, form and change rapidly, while other bone tissues, such as human tooth dentine, develop slowly and maintain constant composition and architecture for entire lifetimes. When studying apatite mineral microarchitecture, mineral distributions or mineralization activity of bone-forming cells, representative samples of tissue are best studied at submicrometre resolution while minimizing sample-preparation damage. Here, we demonstrate the power of ptychographic X-ray tomography to map variations in the mineral content distribution in three dimensions and at the nanometre scale. Using this non-destructive method, we observe nanostructures surrounding hollow tracts that exist in human dentine forming dentinal tubules. We reveal unprecedented quantitative details of the ultrastructure clearly revealing the spatially varying mineralization density. Such information is essential for understanding a variety of natural and therapeutic effects for example in bone tissue healing and ageing.

Scanning electron microscopy (SEM) and X-ray dispersive spectrometry evaluation of direct laser metal sintering surface and human bone interface: a case series.

PubMed

Mangano, Carlo; Piattelli, Adriano; Raspanti, Mario; Mangano, Francesco; Cassoni, Alessandra; Iezzi, Giovanna; Shibli, Jamil Awad

2011-01-01

Recent studies have shown that direct laser metal sintering (DLMS) produces structures with complex geometry and consequently that allow better osteoconductive properties. The aim of this patient report was to evaluate the early bone response to DLMS implant surface retrieved from human jaws. Four experimental DLMS implants were inserted in the posterior mandible of four patients during conventional dental implant surgery. After 8 weeks, the micro-implants and the surrounding tissue were removed and prepared for scanning electron microscopy (SEM) and histomorphometric analysis to evaluate the bone-implant interface. The SEM and EDX evaluations showed a newly formed tissue composed of calcium and phosphorus. The bone-to-implant contact presented a mean of 60.5 ± 11.6%. Within the limits of this patient report, data suggest that the DLMS surfaces presented a close contact with the human bone after a healing period of 8 weeks.

Human fallopian tube mesenchymal stromal cells enhance bone regeneration in a xenotransplanted model.

PubMed

Jazedje, Tatiana; Bueno, Daniela F; Almada, Bruno V P; Caetano, Heloisa; Czeresnia, Carlos E; Perin, Paulo M; Halpern, Silvio; Maluf, Mariangela; Evangelista, Lucila P; Nisenbaum, Marcelo G; Martins, Marília T; Passos-Bueno, Maria R; Zatz, Mayana

2012-06-01

We have recently reported that human fallopian tubes, which are discarded during surgical procedures of women submitted to sterilization or hysterectomies, are a rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has been previously shown that human mesenchymal stromal cells may be useful in enhancing the speed of bone regeneration. This prompted us to investigate whether htMSCs might be useful for the treatment of osteoporosis or other bone diseases, since they present a pronounced capacity for osteogenic differentiation in vitro. Based on this prior knowledge, our aim was to evaluate, in vivo, the osteogenic capacity of htMSCs to regenerate bone through an already described xenotransplantation model: nonimmunosuppressed (NIS) rats with cranial defects. htMSCs were obtained from five 30-50 years old healthy women and characterized by flow cytometry and for their multipotenciality in vitro capacity (osteogenic, chondrogenic and adipogenic differentiations). Two symmetric full-thickness cranial defects on each parietal region of seven NIS rats were performed. The left side (LS) of six animals was covered with CellCeram (Scaffdex)-a bioabsorbable ceramic composite scaffold that contains 60% hydroxyapatite and 40% β-tricalciumphosphate-only, and the right side (RS) with the CellCeram and htMSCs (10(6) cells/scaffold). The animals were euthanized at 30, 60 and 90 days postoperatively and cranial tissue samples were taken for histological analysis. After 90 days we observed neobone formation in both sides. However, in animals euthanized 30 and 60 days after the procedure, a mature bone was observed only on the side with htMSCs. PCR and immunofluorescence analysis confirmed the presence of human DNA and thus that human cells were not rejected, which further supports the imunomodulatory property of htMSCs. In conclusion, htMSCs can be used successfully to enhance bone regeneration in vivo, opening a new field for future treatments of osteoporosis and bone reconstruction.

Geology and preliminary dating of the hominid-bearing sedimentary fill of the Sima de los Huesos Chamber, Cueva Mayor of the Sierra de Atapuerca, Burgos, Spain.

PubMed

Bischoff, J L; Fitzpatrick, J A; León, L; Arsuagà, J L; Falgueres, C; Bahain, J J; Bullen, T

1997-01-01

Sediments of the Sima de los Huesos vary greatly over distances of a few meters. This is typical of interior cave facies, and caused by cycles of cut and fill. Mud breccias containing human bones, grading upwards to mud containing bear bones, fill an irregular surface cut into basal marks and sands. The lack of Bedding and the chaotic abundance of fragile speleothem clasts in the fossiliferous muds suggests that the deposit was originally a subterranean pond facies, and that after emplacement of the human remains, underwent vigorous post-depositional rotation and collapse and brecciation, caused by underlying bedrock dissolution and undermining. The fossiliferous deposits are capped by flowstone and guano-bearing muds which lack large-mammal fossils. U-series and radiocarbon dating indicates the capping flowstones formed from about 68 ka to about 25 ka. U-series analyses of speleothem clasts among the human fossils indicate that all are at, or close to, isotopic equilibrium (> 350 ka). The distribution of U-series dates for 25 bear bones (154 +/- 66 ka) and for 16 human bones (148 +/- 34 ka) is similar and rather broad. Because the human bones seem to be stratigraphically older than chose of the bears, the results would indicate that most of the bones have been accumulating uranium irregularly with time. Electron spin resonance (ESR) analyses of six selected bear bones indicates dates of 189 +/- 28 ka, for which each is cordant with their corresponding U-series date (181 +/- 41 ka). Combined ESR and U-series dates for these samples yielded 200 +/- 4 ka. Such agreement is highly suggestive that uranium uptake in these bones was close to the early-uptake (EU) model, and the dates are essentially correct. Another three selected samples yielded combined ESR U-series dates of 320 +/- 4 ka with a modeled intermediate-mode of uranium uptake. The dating results, therefore, seem to provide a firm minimum age of about 200 ka for the human entry: and suggestive evidence of entry before 320 ka.

Geology and preliminary dating of the hominid-bearing sedimentary fill of the Sima de los Huesos Chamber, Cueva Mayor of the Sierra de Atapuerca, Burgos, Spain

USGS Publications Warehouse

Bischoff, J.L.; Fitzpatrick, J.A.; Leon, L.; Arsuaga, J.L.; Falgueres, Christophe; Bahain, J.-J.; Bullen, T.

1997-01-01

Sediments of the Sima de los Huesos vary greatly over distances of a few meters. This is typical of interior cave facies, and caused by cycles of cut and fill. Mud breccias containing human bones, grading upwards to mud containing bear bones, fill an irregular surface cut into basal marls and sands. The lack of bedding and the chaotic abundance of fragile speleothem clasts in the fossiliferous muds suggests that the deposit was originally a subterranean pond facies, and that after emplacement of the human remains, underwent vigorous post-depositional rotation and collapse and brecciation, caused by underlying bedrock dissolution and undermining. The fossiliferous deposits are capped by flowstone and guano-bearing muds which lack large-mammal fossils. U-series and radiocarbon dating indicates the capping flowstones formed from about 68 ka to about 25 ka. U-series analyses of speleothem clasts among the human fossils indicate that all are at, or close to, isotopic equilibrium (>350 ka). The distribution of U-series dates for 25 bear bones (154??66ka) and for 16 human bones (148??34 ka) is similar and rather broad. Because the human bones seem to be stratigraphically older than those of the bears, the results would indicate that most of the bones have been accumulating uranium irregularly with time. Electron spin resonance (ESR) analyses of six selected bear bones indicates dates of 189??28 ka, for which each is concordant with their corresponding U-series date (181??41 ka). Combined ESR and U-series dates for these samples yielded 200??4 ka. Such agreement is highly suggestive that uranium uptake in these bones was close to the early-uptake (EU) model, and the dates are essentially correct. Another three selected samples yielded combined ESR-U-series dates of 320??4 ka with a modeled intermediate-mode of uranium uptake. The dating results, therefore, seem to provide a firm minimum age of about 200 ka for the human entry; and suggestive evidence of entry before 320 ka. ?? 1997 Academic Press Limited.

42 CFR 121.13 - Definition of human organ under section 301 of the National Organ Transplant Act of 1984, as...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 1984, as amended, means the human (including fetal) kidney, liver, heart, lung, pancreas, bone marrow, cornea, eye, bone, skin, intestine (including the esophagus, stomach, small and/or large intestine, or...

42 CFR 121.13 - Definition of human organ under section 301 of the National Organ Transplant Act of 1984, as...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 1984, as amended, means the human (including fetal) kidney, liver, heart, lung, pancreas, bone marrow, cornea, eye, bone, skin, intestine (including the esophagus, stomach, small and/or large intestine, or...

Osteoblast Specific Overexpression of Human Interleukin-7 Rescues the Bone Mass Phenotype of Interleukin-7 Deficient Female Mice

PubMed Central

Aguila, Hector L.; Mun, Se Hwan; Kalinowski, Judith; Adams, Douglas J.; Lorenzo, Joseph A.; Lee, Sun-Kyeong

2012-01-01

Interleukin-7 is a critical cytokine for lymphoid development and a direct inhibitor of in vitro osteoclastogenesis in murine bone marrow cultures. To explore the role of IL-7 in bone, we generated transgenic mouse lines bearing the 2.3 Kb rat collagen 1A1 promoter driving the expression of human IL-7 specifically in osteoblasts. In addition we crossed these mice with IL-7 deficient mice to determine if the alterations in lymphopoiesis, bone mass and osteoclast formation observed in the IL-7 KO mice could be rescued by osteoblast-specific overexpression of IL-7. Here we show that mice overexpressing human IL-7 in the osteoblast lineage demonstrated increased trabecular bone volume in vivo by µCT and decreased osteoclast formation in vitro. Furthermore, targeted overexpression of IL-7 in osteoblasts rescued the osteopenic bone phenotype and B cell development of IL-7 KO mice but did not have an effect on T lymphopoiesis, which occurs in the periphery. The bone phenotypes in IL-7 KO mice and targeted IL-7 overexpressing mouse models were observed only in females. These results likely reflect both a direct inhibitory effects of IL-7 on osteoclastogenesis in vivo and gender specific differences in responses to IL-7. PMID:22258693

In Vitro Impact of Conditioned Medium From Demineralized Freeze-Dried Bone on Human Umbilical Endothelial Cells.

PubMed

Harnik, Branko; Miron, Richard J; Buser, Daniel; Gruber, Reinhard

2017-03-01

Angiogenesis is essential for the consolidation of bone allografts. The underlying molecular mechanism, however, remains unclear. Soluble factors released from demineralized freeze-dried bone target mesenchymal cells; however, their effect on endothelial cells has not been investigated so far. The aim of the present study was therefore to examine the effect of conditioned medium from demineralized freeze-dried bone on human umbilical endothelial cells in vitro. Conditioned medium was first prepared from demineralized freeze-dried bone following 24 hours incubation at room temperature to produce demineralized bone conditioned media. Thereafter, conditioned medium was used to stimulate human umbilical vein endothelial cells in vitro by determining the cell response based on viability, proliferation, expression of apoptotic genes, a Boyden chamber to determine cell migration, and the formation of branches. The authors report here that conditioned medium decreased viability and proliferation of endothelial cells. Neither of the apoptotic marker genes was significantly altered when endothelial cells were exposed to conditioned medium. The Boyden chamber revealed that endothelial cells migrate toward conditioned medium. Moreover, conditioned medium moderately stimulated the formation of branches. These findings support the concept that conditioned medium from demineralized freeze-dried bone targets endothelial cells by decreasing their proliferation and enhancing their motility under these in vitro conditions.

Overexpression of Human Bone Alkaline Phosphatase in Pichia Pastoris

NASA Technical Reports Server (NTRS)

Karr, Laurel; Malone, Christine, C.; Rose, M. Franklin (Technical Monitor)

2000-01-01

The Pichiapastoris expression system was utilized to produce functionally active human bone alkaline phosphatase in gram quantities. Bone alkaline phosphatase is a key enzyme in bone formation and biomineralization, yet important questions about its structural chemistry and interactions with other cellular enzymes in mineralizing tissues remain unanswered. A soluble form of human bone alkaline phosphatase was constructed by deletion of the 25 amino acid hydrophobic C-terminal region of the encoding cDNA and inserted into the X-33 Pichiapastoris strain. An overexpression system was developed in shake flasks and converted to large-scale fermentation. Alkaline phosphatase was secreted into the medium to a level of 32mgAL when cultured in shake flasks. Enzyme activity was 12U/mg measured by a spectrophotometric assay. Fermentation yielded 880mgAL with enzymatic activity of 968U/mg. Gel electrophoresis analysis indicates that greater than 50% of the total protein in the fermentation is alkaline phosphatase. A purification scheme has been developed using ammonium sulfate precipitation followed by hydrophobic interaction chromatography. We are currently screening crystallization conditions of the purified recombinant protein for subsequent X-ray diffraction analyses. Structural data should provide additional information on the role of alkaline phosphatase in normal bone mineralization and in certain bone mineralization anomalies.

Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound

NASA Astrophysics Data System (ADS)

Moros, Eduardo G.; Novak, Petr; Straube, William L.; Kolluri, Prashant; Yablonskiy, Dmitriy A.; Myerson, Robert J.

2004-03-01

The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue-bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue-bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater than fourfold) were induced in soft tissue-like phantom materials adjacent (within ~5 mm) to a bovine bone as compared to similar experiments without bone inclusions. For low-power long-exposure experiments, where thermal conduction effects are significant, the thermal impact of bone reached at distances >10 mm from the bone surface (upstream of the bone). Therefore, we hypothesize that underlying bone exposed to planar ultrasound hyperthermia creates a high-temperature thermal boundary at depth that compensates for beam attenuation, thus producing more uniform temperature distribution in the intervening tissue layers. With appropriate technology, this finding may lead to improved thermal doses in superficial treatment sites such as the chest wall and the head/neck.

Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease.

PubMed

Rhee, Siyeon; Chung, Jae I; King, Devin A; D'amato, Gaetano; Paik, David T; Duan, Anna; Chang, Andrew; Nagelberg, Danielle; Sharma, Bikram; Jeong, Youngtae; Diehn, Maximilian; Wu, Joseph C; Morrison, Ashby J; Red-Horse, Kristy

2018-01-25

During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion of the Ino80 chromatin remodeler in vascular endothelial cells prevents ventricular compaction in the developing mouse heart. This correlates with defective coronary vascularization, and specific deletion of Ino80 in the two major coronary progenitor tissues-sinus venosus and endocardium-causes intermediate phenotypes. In vitro, endothelial cells promote myocardial expansion independently of blood flow in an Ino80-dependent manner. Ino80 deletion increases the expression of E2F-activated genes and endothelial cell S-phase occupancy. Thus, Ino80 is essential for coronary angiogenesis and allows coronary vessels to support proper compaction of the heart wall.

Bone augmentation for cancellous bone- development of a new animal model

PubMed Central

2013-01-01

Background Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep. Methods The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (∅ 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation. Results The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples. Conclusions This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty. PMID:23819858

Bone augmentation for cancellous bone- development of a new animal model.

PubMed

Klein, Karina; Zamparo, Enrico; Kronen, Peter W; Kämpf, Katharina; Makara, Mariano; Steffen, Thomas; von Rechenberg, Brigitte

2013-07-02

Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep. The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (Ø 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation. The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples. This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty.

The Endocrine Role of Estrogens on Human Male Skeleton

PubMed Central

Rochira, Vincenzo; Kara, Elda; Carani, Cesare

2015-01-01

Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men. PMID:25873947

Construction of human induced pluripotent stem cell-derived oriented bone matrix microstructure by using in vitro engineered anisotropic culture model.

PubMed

Ozasa, Ryosuke; Matsugaki, Aira; Isobe, Yoshihiro; Saku, Taro; Yun, Hui-Suk; Nakano, Takayoshi

2018-02-01

Bone tissue has anisotropic microstructure based on collagen/biological apatite orientation, which plays essential roles in the mechanical and biological functions of bone. However, obtaining an appropriate anisotropic microstructure during the bone regeneration process remains a great challenging. A powerful strategy for the control of both differentiation and structural development of newly-formed bone is required in bone tissue engineering, in order to realize functional bone tissue regeneration. In this study, we developed a novel anisotropic culture model by combining human induced pluripotent stem cells (hiPSCs) and artificially-controlled oriented collagen scaffold. The oriented collagen scaffold allowed hiPSCs-derived osteoblast alignment and further construction of anisotropic bone matrix which mimics the bone tissue microstructure. To the best of our knowledge, this is the first report showing the construction of bone mimetic anisotropic bone matrix microstructure from hiPSCs. Moreover, we demonstrated for the first time that the hiPSCs-derived osteoblasts possess a high level of intact functionality to regulate cell alignment. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 360-369, 2018. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

The biomechanical effect of artificial and human bone density on stopping and stripping torque during screw insertion.

PubMed

Tsuji, Matthew; Crookshank, Meghan; Olsen, Michael; Schemitsch, Emil H; Zdero, Rad

2013-06-01

Orthopedic surgeons apply torque to metal screws manually by "subjective feel" to obtain adequate fracture fixation, i.e. stopping torque, and attempt to avoid accidental over-tightening that leads to screw-bone interface failure, i.e. stripping torque. Few studies have quantified stripping torque in human bone, and only one older study from 1980 reported stopping/ stripping torque ratio. The present aim was to measure stopping and stripping torque of cortical and cancellous screws in artificial and human bone over a wide range of densities. Sawbone blocks were obtained having densities from 0.08 to 0.80g/cm(3). Sixteen fresh-frozen human femurs of known standardized bone mineral density (sBMD) were also used. Using a torque screwdriver, 3.5-mm diameter cortical screws and 6.5-mm diameter cancellous screws were inserted for adequate tightening as determined subjectively by an orthopedic surgeon, i.e. stopping torque, and then further tightened until failure of the screw-bone interface, i.e. stripping torque. There were weak (R=0.25) to strong (R=0.99) linear correlations of absolute and normalized torque vs. density or sBMD. Maximum stopping torques normalized by screw thread area engaged by the host material were 15.2N/mm (cortical screws) and 13.4N/mm (cancellous screws) in sawbone blocks and 20.9N/mm (cortical screws) and 6.1N/mm (cancellous screws) in human femurs. Maximum stripping torques normalized by screw thread area engaged by the host material were 23.4N/mm (cortical screws) and 16.8N/mm (cancellous screws) in sawbone blocks and 29.3N/mm (cortical screws) and 8.3N/mm (cancellous screws) in human femurs. Combined average stopping/ stripping torque ratios were 80.8% (cortical screws) and 76.8% (cancellous screws) in sawbone blocks, as well as 66.6% (cortical screws) and 84.5% (cancellous screws) in human femurs. Surgeons should be aware of stripping torque limits for human femurs and monitor stopping torque during surgery. This is the first study of the effect of sawbone density or human bone sBMD on stopping and stripping torque. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multipotent human stromal cells isolated from cord blood, term placenta and adult bone marrow show distinct differences in gene expression pattern

PubMed Central

Matigian, Nicholas; Brooke, Gary; Zaibak, Faten; Rossetti, Tony; Kollar, Katarina; Pelekanos, Rebecca; Heazlewood, Celena; Mackay-Sim, Alan; Wells, Christine A.; Atkinson, Kerry

2014-01-01

Multipotent mesenchymal stromal cells derived from human placenta (pMSCs), and unrestricted somatic stem cells (USSCs) derived from cord blood share many properties with human bone marrow-derived mesenchymal stromal cells (bmMSCs) and are currently in clinical trials for a wide range of clinical settings. Here we present gene expression profiles of human cord blood-derived unrestricted somatic stem cells (USSCs), human placental-derived mesenchymal stem cells (hpMSCs), and human bone marrow-derived mesenchymal stromal cells (bmMSCs), all derived from four different donors. The microarray data are available on the ArrayExpress database (www.ebi.ac.uk/arrayexpress) under accession number E-TABM-880. Additionally, the data has been integrated into a public portal, www.stemformatics.org. Our data provide a resource for understanding the differences in MSCs derived from different tissues. PMID:26484151

Ectopic bone regeneration by human bone marrow mononucleated cells, undifferentiated and osteogenically differentiated bone marrow mesenchymal stem cells in beta-tricalcium phosphate scaffolds.

PubMed

Ye, Xinhai; Yin, Xiaofan; Yang, Dawei; Tan, Jian; Liu, Guangpeng

2012-07-01

Tissue engineering approaches using the combination of porous ceramics and bone marrow mesenchymal stem cells (BMSCs) represent a promising bone substitute for repairing large bone defects. Nevertheless, optimal conditions for constructing tissue-engineered bone have yet to be determined. It remains unclear if transplantation of predifferentiated BMSCs is superior to undifferentiated BMSCs or freshly isolated bone marrow mononucleated cells (BMNCs) in terms of new bone formation in vivo. The aim of this study was to investigate the effect of in vitro osteogenic differentiation (β-glycerophosphate, dexamethasone, and l-ascorbic acid) of human BMSCs on the capability to form tissue-engineered bone in unloaded conditions after subcutaneous implantation in nude mice. After isolation from human bone marrow aspirates, BMNCs were divided into three parts: one part was seeded onto porous beta-tricalcium phosphate ceramics immediately and transplanted in a heterotopic nude mice model; two parts were expanded in vitro to passage 2 before cell seeding and in vivo transplantation, either under osteogenic conditions or not. Animals were sacrificed for micro-CT and histological evaluation at 4, 8, 12, 16, and 20 weeks postimplantation. The results showed that BMSCs differentiated into osteo-progenitor cells after induction, as evidenced by the altered cell morphology and elevated alkaline phosphatase activity and calcium deposition, but their clonogenicity, proliferating rate, and seeding efficacy were not significantly affected by osteogenic differentiation, compared with undifferentiated cells. Extensive new bone formed in the pores of all the scaffolds seeded with predifferentiated BMSCs at 4 weeks after implantation, and maintained for 20 weeks. On the contrary, scaffolds containing undifferentiated BMSCs revealed limited bone formation only in 1 out of 6 cases at 8 weeks, and maintained for 4 weeks. For scaffolds with BMNCs, woven bone was observed sporadically only in one case at 8 weeks. Overall, this study suggests that ectopic osteogenesis of cell/scaffold composites is more dependent on the in vitro expansion condition, and osteo-differentiated BMSCs hold the highest potential concerning in vivo bone regeneration.

Fractography of human intact long bone by bending.

PubMed

Kimura, T; Ogawa, K; Kamiya, M

1977-05-27

Human intact tibiae were tested using the static bending method to learn about the relationship between the fracture surface and the failure mode. The bending test was applied to test pieces and to whole bones. The fracture surface was observed by scanning electron microscopy. The bone fracture is closely related to the architecture of the bone substance, especially to the direction of the Haversian canals and the lamellae. The failure mode and the sequence of the break line of the bone can be found out by the observation on the fracture surface. Hardly any crushing effects caused by the compressive force is seen. The mechanical properties of the fractured bone can be estimated to some extend by considering the direction of the break line and the failure mode. The strength calculated by the simple beam formula for elastic materials can not be obtained directly because of the plastic deformation of the bone. The results of the tensile test may be applied to the fracture using the static bending moment.

Acute human parvovirus b19 infection: cytologic diagnosis.

PubMed

Sharada Raju, Rane; Nalini Vinayak, Kadgi; Madhusudan Bapat, Vishnuprasad; Preeti Balkisanji, Agrawal; Shaila Chandrakant, Puranik

2014-09-01

Human parvovirus B19 is highly tropic to human bone marrow and replicates only in erythroid progenitor cells. It is causative agent of transient aplastic crisis in patients with chronic haemolytic anemia. In immunocompromised patients persistent parvovirus B19 infection may develop and it manifests as pure red cell aplasia and chronic anaemia. Bone marrow is characterised morphologically by giant pronormoblast stage with little or no further maturation. We encountered a case of 6 year old HIV positive male child presented with pure red cell aplasia due to parvovirus B19 infection. Bone marrow aspiration cytology revealed giant pronormoblast with prominent intranuclear inclusions led to suspicion of parvovirus B19 infection which was confirmed by DNA PCR. This case is presented to report classical morphological features of parvovirus B19 infection rarely seen on bone marrow examination should warrant the suspicion of human parvovirus B19 infection in the setting of HIV positive patient with repeated transfusions and confirmation should be done by PCR.

Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels

PubMed Central

Chang, Ming-Kang; Kramer, Ina; Huber, Thomas; Kinzel, Bernd; Guth-Gundel, Sabine; Leupin, Olivier; Kneissel, Michaela

2014-01-01

We identified previously in vitro LRP4 (low-density lipoprotein receptor-related protein 4) as a facilitator of the WNT (Wingless-type) antagonist sclerostin and found mutations disrupting this function to be associated with high bone mass in humans similar to patients lacking sclerostin. To further delineate the role of LRP4 in bone in vivo, we generated mice lacking Lrp4 in osteoblasts/osteocytes or osteocytes only. Lrp4 deficiency promoted progressive cancellous and cortical bone gain in both mutants, although more pronouncedly in mice deficient in osteoblast/osteocyte Lrp4, consistent with our observation in human bone that LRP4 is most strongly expressed by osteoblasts and early osteocytes. Bone gain was related primarily to increased bone formation. Interestingly, Lrp4 deficiency in bone dramatically elevated serum sclerostin levels whereas bone expression of Sost encoding for sclerostin was unaltered, indicating that osteoblastic Lrp4 retains sclerostin within bone. Moreover, we generated anti-LRP4 antibodies selectively blocking sclerostin facilitator function while leaving unperturbed LRP4–agrin interaction, which is essential for neuromuscular junction function. These antibodies increased bone formation and thus cancellous and cortical bone mass in skeletally mature rodents. Together, we demonstrate a pivotal role of LRP4 in bone homeostasis by retaining and facilitating sclerostin action locally and provide a novel avenue to bone anabolic therapy by antagonizing LRP4 sclerostin facilitator function. PMID:25404300

Cortical Porosity Identifies Women with Osteopenia at Increased Risk for Forearm Fractures

PubMed Central

Bala, Yohann; Zebaze, Roger; Ghasem-Zadeh, Ali; Atkinson, Elizabeth J.; Iuliano, Sandra; Peterson, James M.; Amin, Shreyasee; Bjørnerem, Åshild; Melton, L. Joseph; Johansson, Helena; Kanis, John A.; Khosla, Sundeep; Seeman, Ego

2014-01-01

Background Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. Methods We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high-resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10-year fracture probability using the country-specific FRAX tool in 68 postmenopausal women with forearm fractures and 70 age-matched community controls in Olmsted County, Minnesota. Results Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact-appearing cortical porosity predicted fracture independent of aBMD; odds ratio [OR] 1.92 (95%CI, 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with, from those without, fractures because high porosity was present in 92% and 86% of each group respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact-appearing cortex conferred an OR for fracture of 4.00 (95%CI, 1.15–13.90). Conclusion In women with osteoporosis, porosity is captured by aBMD and so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. PMID:24519558

Anatomic study on mental canal and incisive nerve canal in interforaminal region in Chinese population.

PubMed

Xu, Yun; Suo, Ning; Tian, Xiufen; Li, Fei; Zhong, Guangxin; Liu, Xiaoran; Bao, Yongxing; Song, Tao; Tian, Hua

2015-08-01

This study was aimed to detect the positions of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region in Chinese population to supply the reference data of the surgical safe zone in chin for clinicians. A total of 80 formalin-fixed semi-mandibles of Chinese adult cadavers were dissected, the positions and courses of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region were measured. The mental foramina were present in all cases (100 %), and most of them were located below 2nd premolar (58.75 %). Accessory mental foramina were observed in 5 %. The anterior end of mandibular canal, extending along the course of 7.37 ± 1.10 mm above the lower border of mandible to interforaminal region about 3.54 ± 0.70 mm medial to the mental foramen, most often ended below between the two premolars (73.75 %), where it continued as the incisive nerve canal (100 %) and the mental canal (96.25 %). Mental canal, with the wall formed by compact bone, being 2.60 ± 0.60 mm in diameter and 4.01 ± 1.20 mm in length, opened into mental foramen. Incisive nerve canal, with the wall formed by thin compact bone and/or partly or completely by spongy bone, being 1.76 ± 0.27 mm in diameter and 24.87 ± 2.23 mm in length, extended to the incisor region along the course of 9.53 ± 1.43 mm above the lower border of mandible, and most often ended below the lateral incisor (70.00 %). This research recommended for chin operations in Chinese population: the surgical safe zone could be set in the region about over 4 mm anterior to the mental foramen, and over 12 mm above inferior border of mandible for anterior alveolar surgery, or within 9 mm above inferior border of mandible for genioplasty.

Abnormal bone formation induced by implantation of osteosarcoma-derived bone-inducing substance in the X-linked hypophosphatemic mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshikawa, H.; Masuhara, K.; Takaoka, K.

1985-01-01

The X-linked hypophosphatemic mouse (Hyp) has been proposed as a model for the human familial hypophosphatemia (the most common form of vitamin D-resistant rickets). An osteosarcoma-derived bone-inducing substance was subcutaneously implanted into the Hyp mouse. The implant was consistently replaced by cartilage tissue at 2 weeks after implantation. The cartilage matrix seemed to be normal, according to the histological examination, and 35sulphur (TVS) uptake was also normal. Up to 4 weeks after implantation the cartilage matrix was completely replaced by unmineralized bone matrix and hematopoietic bone marrow. Osteoid tissue arising from the implantation of bone inducing substance in the Hypmore » mouse showed no radiologic or histologic sign of calcification. These findings suggest that the abnormalities of endochondral ossification in the Hyp mouse might be characterized by the failure of mineralization in cartilage and bone matrix. Analysis of the effects of bone-inducing substance on the Hyp mouse may help to give greater insight into the mechanism and treatment of human familial hypophosphatemia.« less

Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton

PubMed Central

Yue, Rui; Shen, Bo; Morrison, Sean J

2016-01-01

Bone marrow stromal cells maintain the adult skeleton by forming osteoblasts throughout life that regenerate bone and repair fractures. We discovered that subsets of these stromal cells, osteoblasts, osteocytes, and hypertrophic chondrocytes secrete a C-type lectin domain protein, Clec11a, which promotes osteogenesis. Clec11a-deficient mice appeared developmentally normal and had normal hematopoiesis but reduced limb and vertebral bone. Clec11a-deficient mice exhibited accelerated bone loss during aging, reduced bone strength, and delayed fracture healing. Bone marrow stromal cells from Clec11a-deficient mice showed impaired osteogenic differentiation, but normal adipogenic and chondrogenic differentiation. Recombinant Clec11a promoted osteogenesis by stromal cells in culture and increased bone mass in osteoporotic mice in vivo. Recombinant human Clec11a promoted osteogenesis by human bone marrow stromal cells in culture and in vivo. Clec11a thus maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. In light of this, we propose to call this factor Osteolectin. DOI: http://dx.doi.org/10.7554/eLife.18782.001 PMID:27976999

Investigating the Effect of Compaction Characteristics on the Erodibility of Cohesive Soils Using the JET Method

NASA Astrophysics Data System (ADS)

Asghari Tabrizi, A.; LaRocque, L. A.; Chaudhry, M.; Imran, J.

2013-12-01

Several flood disasters occur every year all over the world, mostly due to levee and dam failure which result in human fatalities as well as devastating economic damages. To model and predict earthen embankment failures for the preparation of emergency action plans and risk assessments, the soil erodibility by flowing water is an essential parameter. The determination of erodibility becomes even more complicated for cohesive soils because of the large number of parameters controlling their erosion behavior (e.g. clay content, plasticity, compaction effort, compaction water content) and the difficulty of estimating these parameters. In this study the effect of the compaction energy and compaction water content on the erodibility of a sandy loam soil was assessed. Soil samples were prepared in a standard diameter compaction mold, 101.6 mm, for three levels of compaction effort and water content (i.e. low, medium, and high) with two replications for each case (18 tests total) and examined using the jet erosion test (JET). Observations from qualitative and statistical analyses of the data are: 1) a wide range of erodibility, from very erodible to very resistant, was produced by changes in the compaction characteristics; 2) for a given compaction energy, the erosion resistance based on the detachment rate coefficient kd tends to become minimum near the optimum compaction water content. On the dry side of optimum compaction water content, kd decreases with steep gradients by increasing the water content, while it increases with a flatter gradient on the wet side; 3) At a given water content, the soil erosion resistance increases with compaction efforts; 4) compaction water content influences soil erosibility more than compaction energy, especially on the dry side of the optimum compaction water content; and 5) for a given compaction effort, the critical shear stress increases with water content up to an optimum water content and then it decreases which is in consistent with the kd trends.

Animal models for bone tissue engineering and modelling disease

PubMed Central

Griffin, Michelle

2018-01-01

ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

Skeletal dosimetry based on µCT images of trabecular bone: update and comparisons

NASA Astrophysics Data System (ADS)

Kramer, R.; Cassola, V. F.; Vieira, J. W.; Khoury, H. J.; de Oliveira Lira, C. A. B.; Robson Brown, K.

2012-06-01

Two skeletal dosimetry methods using µCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic-periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use µCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 µm thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the µCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal tissues calculated with the SPC and the PIRT method and AM and BE absorbed doses and AFs calculated with PIRT-based DRFs and with the SPC method. The results calculated with the two skeletal dosimetry methods agree well if one takes the differences between the two models properly into account. Additionally, the SPC method will be updated with larger µCT images of TB.

Automated cortical bone segmentation for multirow-detector CT imaging with validation and application to human studies

PubMed Central

Li, Cheng; Jin, Dakai; Chen, Cheng; Letuchy, Elena M.; Janz, Kathleen F.; Burns, Trudy L.; Torner, James C; Levy, Steven M.; Saha, Punam K

2015-01-01

Purpose: Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow-detector CT (MD-CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal-to-noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD-CT imaging is presented and its performance and application are examined. Methods: The algorithm is completed in two major steps—(1) bone filling, alignment, and region-of-interest computation and (2) segmentation of cortical bone. After the first step, the following sequence of tasks is performed to accomplish cortical bone segmentation—(1) detection of marrow space and possible pores, (2) computation of cortical bone thickness, detection of recession points, and confirmation and filling of true pores, and (3) detection of endosteal boundary and delineation of cortical bone. Effective generalizations of several digital topologic and geometric techniques are introduced and a fully automated algorithm is presented for cortical bone segmentation. Results: An accuracy of 95.1% in terms of volume of agreement with manual outlining of cortical bone was observed in human MD-CT scans, while an accuracy of 88.5% was achieved when compared with manual outlining on postregistered high resolution micro-CT imaging. An intraclass correlation coefficient of 0.98 was obtained in cadaveric repeat scans. A pilot study was conducted to describe gender differences in cortical bone properties. This study involved 51 female and 46 male participants (age: 19–20 yr) from the Iowa Bone Development Study. Results from this pilot study suggest that, on average after adjustment for height and weight differences, males have thicker cortex (mean difference 0.33 mm and effect size 0.92 at the anterior region) with lower bone mineral density (mean difference −28.73 mg/cm3 and effect size 1.35 at the posterior region) as compared to females. Conclusions: The algorithm presented is suitable for fully automated segmentation of cortical bone in MD-CT imaging of the distal tibia with high accuracy and reproducibility. Analysis of data from a pilot study demonstrated that the cortical bone indices allow quantification of gender differences in cortical bone from MD-CT imaging. Application to larger population groups, including those with compromised bone, is needed. PMID:26233184

Collective secondary cremation in a pit grave: a unique funerary context in Portuguese Chalcolithic burial practices.

PubMed

Silva, A M; Leandro, I; Pereira, D; Costa, C; Valera, A C

2015-02-01

Perdigões is a large site with a set of ditched enclosures located at Reguengos de Monsaraz, Alentejo, South Portugal. Recently at the central area of this site burnt human remains were found in a pit (#16). This structure had inside human remains, animal bones (namely pig, sheep or goat, cattle, dog, deer and rabbit), shards, ivory idols and arrowheads. All have been subjected to fire and later deposited in that pit, resulting in a secondary disposal of human bones. The recovered fragmented human bones (4845.18 g) correspond to a minimal number of 9 individuals: 6 adults and 3 sub-adults. The aim of this work is to document and interpret this funerary context based on the study of the recovered human remains. For that purpose, observations of all alterations due to fire, such as colour change and type of bone distortion, as well as anthropological data were collected. The data obtained suggest that these human remains were probably intentionally cremated, carefully collected and finally deposited in this pit. The cremation was conducted on probably complete corpses, some of them still fairly fresh and fleshed, as some bones presented thumbnail fractures. The collective cremation of the pit 16 represents an unprecedented funerary context for Portuguese, and Iberian Peninsula, Chalcolithic burial practices. Moreover, it is an example of the increasing diversity of mortuary practices of Chalcolithic human populations described in present Portuguese territory, as well as, in the Iberian Peninsula. Copyright © 2014 Elsevier GmbH. All rights reserved.

On-Command Force and Torque Impeding Devices (OC-FTID) Using ERF

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph; Badescu, Mircea; Sherrit, Stewart

2014-01-01

Various machines have been developed to address the need for countermeasures of bone and muscle deterioration when humans operate over extended time in space. Even though these machines are in use, each of them has many limitations that need to be addressed in an effort to prepare for human missions to distant bodies in the solar system. An exercise exoskeleton was conceived that performs on-demand resistivity by inducing force and torque impedance via ElectroRheological Fluid (ERF). The resistive elements consist of pistons that are moving inside ERF-filled cylinders or a donut-shaped cavity, and the fluid flows through the piston when the piston is moved. Tests of the operation of ERF against load showed the feasibility of this approach. ERF properties of high yield stress, low current density, and fast response (less than one millisecond) offer essential characteristics for the construction of the exoskeleton. ERFs can apply very high electrically controlled resistive forces or torque while their size (weight and geometric parameters) can be very small. Their long life and ability to function in a wide temperature range (from -40 to 200 C) allows for their use in extreme environments. ERFs are also nonabrasive, non-toxic, and nonpolluting (meet health and safety regulations). The technology is applicable as a compact exercise machine for astronauts' countermeasure of microgravity, an exercise machine for sport, or as a device for rehabilitation of patients with limb issues.

Tissue regeneration in dentistry: Can salamanders provide insight?

PubMed

Sader, F; Denis, J-F; Roy, S

2018-05-01

The ability to regenerate damaged tissues would be of tremendous benefit for medicine and dentistry. Unfortunately, humans are unable to regenerate tissues such as teeth and fingers or to repair injured spinal cord. With an aging population, health problems are more prominent and dentistry is no exception as loss of bone tissue in the orofacial sphere from periodontal disease is on the rise. Humans can repair oral soft tissues exceptionally well; however, hard tissues, such as bone and teeth, are devoid of the ability to repair well or at all. Fortunately, Mother Nature has solved nearly every problem that we would like to solve for our own benefit and tissue regeneration is no exception. By studying animals that can regenerate, like Axolotls (Mexican salamander), we hope to find ways to stimulate regeneration in humans. We will discuss the role of the transforming growth factor beta cytokines as they are central to wound healing in humans and regeneration in Axolotls. We will also compare wound healing in humans (skin and oral mucosa) to Axolotl skin wound healing and limb regeneration. Finally, we will address the problem of bone regeneration and present results in salamanders which indicate that in order to regenerate bone you need to recruit non-bone cells. Fundamental research, such as the work being performed in animals that can regenerate, offers insight to help understand why some treatments are successful while others fail when it comes to specific tissues such as bones. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human embryonic stem cell-derived mesodermal progenitors display substantially increased tissue formation compared to human mesenchymal stem cells under dynamic culture conditions in a packed bed/column bioreactor.

PubMed

de Peppo, Giuseppe Maria; Sladkova, Martina; Sjövall, Peter; Palmquist, Anders; Oudina, Karim; Hyllner, Johan; Thomsen, Peter; Petite, Hervé; Karlsson, Camilla

2013-01-01

Bone tissue engineering represents a promising strategy to obviate bone deficiencies, allowing the ex vivo construction of bone substitutes with unprecedented potential in the clinical practice. Considering that in the human body cells are constantly stimulated by chemical and mechanical stimuli, the use of bioreactor is emerging as an essential factor for providing the proper environment for the reproducible and large-scale production of the engineered substitutes. Human mesenchymal stem cells (hMSCs) are experimentally relevant cells but, regardless the encouraging results reported after culture under dynamic conditions in bioreactors, show important limitations for tissue engineering applications, especially considering their limited proliferative potential, loss of functionality following protracted expansion, and decline in cellular fitness associated with aging. On the other hand, we previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold great potential to provide a homogenous and unlimited source of cells for bone engineering applications. Based on prior scientific evidence using different types of stem cells, in the present study we hypothesized that dynamic culture of hES-MPs in a packed bed/column bioreactor had the potential to affect proliferation, expression of genes involved in osteogenic differentiation, and matrix mineralization, therefore resulting in increased bone-like tissue formation. The reported findings suggest that hES-MPs constitute a suitable alternative cell source to hMSCs and hold great potential for the construction of bone substitutes for tissue engineering applications in clinical settings.

Effects of combined hydroxyapatite and human platelet rich plasma on bone healing in rabbit model: radiological, macroscopical, hidtopathological and biomechanical evaluation.

PubMed

Oryan, A; Meimandi Parizi, A; Shafiei-Sarvestani, Z; Bigham, A S

2012-12-01

Hydroxyapatite is an osteoconductive material used as a bone graft extender and exhibits excellent biocompatibility with soft tissues such as skin, muscle and gums, making it an ideal candidate for orthopedic and dental implants or components of implants. Synthetic hydroxyapatite has been widely used in repair of hard tissues, and common uses include bone repair, bone augmentation, as well as coating of implants or acting as fillers in bone or teeth. On the other hand, human platelet rich plasma (hPRP) has been used as a source of osteoinductive factor. A combination of hPRP and hydroxyapatite is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of hydroxyapatite and hPRP on osteogenesis in vivo, using rabbit model bone healing. A critical size defect of 10 mm long was created in the radial diaphysis of 36 rabbit and either supplied with hydroxyapatite-human PRP or hydroxyapatite or was left empty (control group). Radiographs of each forelimb were taken postoperatively on 1st day and then at the 2nd, 4th, 6th and 8th weeks post injury to evaluate bone formation, union and remodeling of the defect. The operated radiuses of half of the animals in each group were removed on 56th postoperative day and were grossly and histopathologically evaluated. In addition, biomechanical test was conducted on the operated and normal forearms of the other half of the animals of each group. This study demonstrated that hydroxyapatite-humanPRP, could promote bone regeneration in critical size defects with a high regenerative capacity. The results of the present study demonstrated that hydroxyapatite-hPRP could be an attractive alternative for reconstruction of the major diaphyseal defects of the long bones in animal models.

The relationship between the mechanical anisotropy of human cortical bone tissue and its microstructure

NASA Astrophysics Data System (ADS)

Espinoza Orias, Alejandro A.

Orthopedics research has made significant advances in the areas of biomechanics, bone implants and bone substitute materials. However, to date there is no definitive model to explain the structure-property relationships in bone as a material to enable better implant designs or to develop a true biomechanical analog of bone. The objective of this investigation was to establish a relationship between the elastic anisotropy of cortical bone tissue and its microstructure. Ultrasonic wave propagation was used to measure stiffness coefficients for specimens sectioned along the length of a human femur. The elastic constants were orthotropic and varied with anatomical location. Stiffness coefficients were generally largest at the midshaft and stiffness anisotropy ratios were largest at the distal and proximal ends. These tests were run on four additional human femurs to assess the influence of phenotypic variation, and in most cases, it was found that phenotypes do not exert a significant effect. Stiffness coefficients were shown to be correlated as a power law relation to apparent density, but anisotropy ratios were not. Texture analysis was performed on selected samples to measure the orientation distribution of the bone mineral crystals. Inverse pole figures showed that bone mineral crystals had a preferred crystallographic orientation, coincident with the long axis of the femur, which is its principal loading direction. The degree of preferred orientation was represented in Multiples of a Random Distribution (MRD), and correlated to the anisotropy ratios. Variation in elastic anisotropy was shown to be primarily due to the bone mineral orientation. The results found in this work can be used to incorporate anisotropy into structural analysis for bone as a material.

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

PubMed

Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

2017-04-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes

PubMed Central

Alam, Imranul; Reilly, Austin M.; Alkhouli, Mohammed; Gerard-O’Riley, Rita L.; Kasipathi, Charishma; Oakes, Dana K.; Wright, Weston B.; Acton, Dena; McQueen, Amie K.; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G.; Econs, Michael J.

2017-01-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice over-expressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions. PMID:28013361

Weightlessness and the human skeleton: A new perspective

NASA Technical Reports Server (NTRS)

Holick, Michael F.

1994-01-01

It is now clear after more than two decades of space exploration that one of the major short- and long-term effects of microgravity on the human body is the loss of bone. The purpose of this presentation will be to review the data regarding the impact of microgravity and bed rest on calcium and bone metabolism. The author takes the position in this Socratic debate that the effect of microgravity on bone metabolism can be either reversed or mitigated. As we begins to contemplate long-duration space flight and habitation of Space Station Freedom and the moon, one of the issues that needs to be addressed is whether humans need to maintain a skeleton that has been adapted for the one-g force on earth. Clearly, in the foreseeable future, a healthy and structurally sound skeleton will be required for astronauts to shuttle back and forth from earth to the moon, space station, and Mars. Based on most available data from bed-rest studies and the short- and long-duration microgravity experiences by astronauts and cosmonauts, bone loss is a fact of life in this environment. With the rapid advances in understanding of bone physiology it is now possible to contemplate measures that can prevent or mitigate microgravity-induced bone loss. Will the new therapeutic approaches for enhancing bone mineralization be useful for preventing significant bone loss during long-term space flight? Are there other approaches such as exercise and electrical stimulation that can be used to mitigate the impact of microgravity on the skeleton? A recent study that evaluated the effect of microgravity on bone modeling in developing chick embryos may perhaps provide a new perspective about the impact of microgravity on bone metabolism.

The morphology of human hyoid bone in relation to sex, age and body proportions.

PubMed

Urbanová, P; Hejna, P; Zátopková, L; Šafr, M

2013-06-01

Morphological aspects of the human hyoid bone are, like many other skeletal elements in human body, greatly affected by individual's sex, age and body proportions. Still, the known sex-dependent bimodality of a number of body size characteristics overshadows the true within-group patterns. Given the ambiguity of the causal effects of age, sex and body size upon hyoid morphology the present study puts the relationship between shape of human hyoid bone and body proportions (height and weight) under scrutiny of a morphological study. Using 211 hyoid bones and landmark-based methods of geometric morphometrics, it was shown that the size of hyoid bones correlated positively with measured body dimensions but showed no correlation if the individual's sex was controlled for. For shape variables, our results revealed that hyoid morphology is clearly related to body size as expressed in terms of the height and weight. Yet, the hyoid shape was shown to result primarily from the sex-related bimodal distribution of studied body size descriptors which, in the case of the height-dependent model, exhibited opposite trends for males and females. Apart from the global hyoid shape given by spatial arrangements of the greater horns, body size dependency was translated into size and position of the hyoid body. None of the body size characters had any impact on hyoid asymmetry. Ultimately, sexually dimorphic variation was revealed for age-dependent changes in both size and shape of hyoid bones as male hyoids tend to be more susceptible to modifications with age than female bones. Copyright © 2013 Elsevier GmbH. All rights reserved.

Maxillary anterior ridge augmentation with recombinant human bone morphogenetic protein 2.

PubMed

Edmunds, Ryan K; Mealey, Brian L; Mills, Michael P; Thoma, Daniel S; Schoolfield, John; Cochran, David L; Mellonig, Jim

2014-01-01

No human studies exist on the use of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an absorbable collagen sponge (ACS) as a sole graft material for lateral ridge augmentation in large ridge defect sites. This series evaluates the treatment outcome of maxillary anterior lateral ridge augmentation with rhBMP-2/ACS. Twenty patients were treated with rhBMP-2/ACS and fixation screws for space maintenance. Cone beam volumetric tomography measurements were used to determine gain in ridge width, and a bone core biopsy was obtained. The mean horizontal ridge gain was 1.2 mm across sites, and every site gained width.