An image-based skeletal tissue model for the ICRP reference newborn

NASA Astrophysics Data System (ADS)

Pafundi, Deanna; Lee, Choonsik; Watchman, Christopher; Bourke, Vincent; Aris, John; Shagina, Natalia; Harrison, John; Fell, Tim; Bolch, Wesley

2009-07-01

Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set—both male and female—that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in mineral bone composition may have significant dosimetric implications when considering localized marrow dosimetry for radionuclides that target mineral bone in the newborn child.

Bioactive scaffold for bone tissue engineering: An in vivo study

NASA Astrophysics Data System (ADS)

Livingston, Treena Lynne

Massive bone loss of the proximal femur is a common problem in revision cases of total hip implants. Allograft is typically used to reconstruct the site for insertion of the new prosthesis. However, for long term fixation and function, it is desirable that the allograft becomes fully replaced by bone tissue and aids in the regeneration of bone to that site. However, allograft use is typically associated with delayed incorporation and poor remodeling. Due to these profound limitations, alternative approaches are needed. Tissue engineering is an attractive approach to designing improved graft materials. By combining osteogenic activity with a resorbable scaffold, bone formation can be stimulated while providing structure and stability to the limb during incorporation and remodeling of the scaffold. Porous, surface modified bioactive ceramic scaffolds (pSMC) have been developed which stimulate the expression of the osteoblastic phenotype and production of bone-like tissue in vitro. The scaffold and two tissue-engineered constructs, osteoprogenitor cells seeded onto scaffolds or cells expanded in culture to form bone tissue on the scaffolds prior to implantation, were investigated in a long bone defect model. The rate of incorporation was assessed. Both tissue-engineered constructs stimulated bone formation and comparable repair at 2 weeks. In a rat femoral window defect model, bone formation increased over time for all groups in concert with scaffold resorption, leading to a 40% increase in bone and 40% reduction of the scaffold in the defect by 12 weeks. Both tissue-engineered constructs enhanced the rate of mechanical repair of long bones due to better bony union with the host cortex. Long bones treated with tissue engineered constructs demonstrated a return in normal torsional properties by 4 weeks as compared to 12 weeks for long bones treated with pSMC. Culture expansion of cells to produce bone tissue in vitro did not accelerate incorporation over the treatment with cells seeded at the time of surgery. Porous, surface modified bioactive ceramic is a promising scaffold material for tissue-engineered bone repair. Bone formation and scaffold resorption act in concert for maintenance and improvement of the structural properties of the long bones over time. As determined histomorphometrically and mechanically, the rate of incorporation of the scaffold was enhanced with the tissue-engineered constructs.

Prefabricated microvascular autograft in tracheal reconstruction.

PubMed

Fayad, J; Kuriloff, D B

1994-10-01

Tracheal reconstruction continues to be a challenge in head and neck surgery. Numerous techniques, including the use of alloplasts, composite grafts, and staged laryngotracheal troughs, have met with limited success because of implant exposure, infection, persistent granulation tissue, and eventual restenosis. With recently introduced techniques for soft-tissue molding, bone induction with bone morphogenetic protein, and microvascular free tissue transfer, a rodent model was developed to create a well-vascularized tracheal autograft. In this model, a rigid tube having the same dimensions and flexibility as the native trachea was created by wrapping a cylindrical silicone tracheal mold with a layer of vascularized adductor thigh muscle pedicled on the femoral vessels in the groin. Tracheal rings were created by filing transverse troughs in the muscle bed with bone morphogenetic protein-primed demineralized bone matrix before wrapping around the silicone mold. Grafts harvested at 2 weeks demonstrated rigid skeletal support provided by heterotopic bone formation in the form of rings and a smooth inner lining produced by fibroplasia. Bone transformation was controlled and restricted to the muscle troughs, allowing intervening regions of soft tissue and thus producing a flexible neotrachia. With this model, a homologous, vascularized tracheal autograft capable of microvascular free tissue transfer was fabricated based on the femoral vessels. Prefabrication of composite grafts, through the use of soft-tissue molding, bone induction, and subsequent free tissue transfer, has an unlimited potential for use in head and neck reconstruction.

Rapid prototyping technology and its application in bone tissue engineering*

PubMed Central

YUAN, Bo; ZHOU, Sheng-yuan; CHEN, Xiong-sheng

2017-01-01

Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects. PMID:28378568

Rapid prototyping technology and its application in bone tissue engineering.

PubMed

Yuan, Bo; Zhou, Sheng-Yuan; Chen, Xiong-Sheng

Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.

Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area.

PubMed

Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

2016-01-01

Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications.

Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area

PubMed Central

Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

2016-01-01

Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID:27279797

A new osteonecrosis animal model of the femoral head induced by microwave heating and repaired with tissue engineered bone

PubMed Central

Han, Rui; Geng, Chengkui; Wang, Yongnian; Wei, Lei

2008-01-01

The objective of this research was to induce a new animal model of osteonecrosis of the femoral head (ONFH) by microwave heating and then repair with tissue engineered bone. The bilateral femoral heads of 84 rabbits were heated by microwave at various temperatures. Tissue engineered bone was used to repair the osteonecrosis of femoral heads induced by microwave heating. The roentgenographic and histological examinations were used to evaluate the results. The femoral heads heated at 55°C for ten minutes showed low density and cystic changes in X-ray photographs, osteonecrosis and repair occurred simultaneously in histology at four and eight weeks, and 69% femoral heads collapsed at 12 weeks. The ability of tissue engineered bone to repair the osteonecrosis was close to that of cancellous bone autograft. The new animal model of ONFH could be induced by microwave heating, and the tissue engineering technique will provide an effective treatment. PMID:18956184

[The method of accelerating osteanagenesis and revascularization of tissue engineered bone in big animal in vivo].

PubMed

Chen, Bin; Pei, Guo-xian; Wang, Ke; Jin, Dan; Wei, Kuan-hai; Ren, Gao-hong

2003-02-01

To study whether tissue engineered bone can repair the large segment bone defect of large animal or not. To observe what character the fascia flap played during the osteanagenesis and revascularization process of tissue engineered bone. 9 Chinese goats were made 2 cm left tibia diaphyseal defect. The repairing effect of the defects was evaluated by ECT, X-ray and histology. 27 goats were divided into three groups: group of CHAP, the defect was filled with coral hydroxyapatite (CHAP); group of tissue engineered bone, the defect was filled with CHAP + bone marrow stroma cells (BMSc); group of fascia flap, the defect was filled with CHAP + BMSc + fascia flap. After finished culturing and inducing the BMSc, CHAP of group of tissue engineered bone and of fascia flap was combined with it. Making fascia flap, different materials as described above were then implanted separately into the defects. Radionuclide bone imaging was used to monitor the revascularization of the implants at 2, 4, 8 weeks after operation. X-ray examination, optical density index of X-ray film, V-G staining of tissue slice of the implants were used at 4, 8, 12 weeks after operation, and the biomechanical character of the specimens were tested at 12 weeks post operation. In the first study, the defect showed no bone regeneration phenomenon. 2 cm tibia defect was an ideal animal model. In the second study, group of CHAP manifested a little trace of bone regeneration, as to group of tissue engineered bone, the defect was almost repaired totally. In group of fascia flap, with the assistance of fascia flap which gave more chance to making implants to get more nutrient, the repair was quite complete. The model of 2 cm caprine tibia diaphyseal defect cannot be repaired by goat itself and can satisfy the tissue engineering's demands. Tissue engineered bone had good ability to repair large segment tibia defect of goat. Fascia flap can accelerate the revascularization process of tissue engineered bone. And by this way, it augment the ability of tissue engineered bone to repair the large bone defect of goat.

Noninvasive Determination of Bone Mechanical Properties using Vibration Response: A Refined Model and Validation in vivo

NASA Technical Reports Server (NTRS)

Roberts, S. G.; Hutchinson, T. M.; Arnaud, S. B.; Steele, C. R.; Kiratli, B. J.; Martin, R. B.

1996-01-01

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical Response Tissue Analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(MRTA) and theoretical EI values for padded aluminum rods was R(exp 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal Bone Mineral Density (BMD) measurements were also made. The relationship between E(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(exp 2) = 0.947) and better than that using the older model (R(exp 2) = 0.645). EI(MRTA) and BMD are also highly correlated (R(exp 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(exp 2) = 0.915 and R(exp 2) = 0.894, respectively). This is the first biological validation of a non-invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

Noninvasive Determination of Bone Mechanical Properties Using Vibration Response: A Refined Model and Validation in vivo

NASA Technical Reports Server (NTRS)

Roberts, S. G.; Hutchinson, T. M.; Arnaud, S. B.; Kiratli, B. J; Steele, C. R.

1996-01-01

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical response tissue analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(sub MRTA) and theoretical EI values for padded aluminum rods was R(sup 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal bone mineral density (BMD) measurements were also made. The relationship between EI(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(sup 2) = 0.947) and better than that using the older model (R(sup 2) = 0.645). EI(sub MRTA) and BMD are also highly correlated (R(sup 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(sup 2) = 0.915 and R(sup 2) = 0.894, respectively). This is the first biological validation of a non- invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

Bone Tissue Collagen Maturity and Mineral Content Increase With Sustained Hyperglycemia in the KK-Ay Murine Model of Type 2 Diabetes.

PubMed

Hunt, Heather B; Pearl, Jared C; Diaz, David R; King, Karen B; Donnelly, Eve

2018-05-01

Type 2 diabetes mellitus (T2DM) increases fracture risk for a given bone mineral density (BMD), which suggests that T2DM changes bone tissue properties independently of bone mass. In this study, we assessed the effects of hyperglycemia on bone tissue compositional properties, enzymatic collagen crosslinks, and advanced glycation end-products (AGEs) in the KK-Ay murine model of T2DM using Fourier transform infrared (FTIR) imaging and high-performance liquid chromatography (HPLC). Compared to KK-aa littermate controls (n = 8), proximal femoral bone tissue of KK-Ay mice (n = 14) exhibited increased collagen maturity, increased mineral content, and less heterogeneous mineral properties. AGE accumulation assessed by the concentration of pentosidine, as well as the concentrations of the nonenzymatic crosslinks hydroxylysylpyridinoline (HP) and lysyl pyridinoline (LP), did not differ in the proximal femurs of KK-Ay mice compared to controls. The observed differences in tissue-level compositional properties in the KK-Ay mice are consistent with bone that is older and echo observations of reduced remodeling in T2DM. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

PubMed

Rubessa, Marcello; Polkoff, Kathryn; Bionaz, Massimo; Monaco, Elisa; Milner, Derek J; Holllister, Scott J; Goldwasser, Michael S; Wheeler, Matthew B

2017-10-02

Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

LASERS IN MEDICINE: Laser diagnostics of biofractals

NASA Astrophysics Data System (ADS)

Ushenko, A. G.

1999-12-01

An optical approach to the problem of modelling and diagnostics of the structures of biofractal formations was considered in relation to human bone tissue. A model was proposed for the optical properties of this tissue, including three levels of fractal organisation: microcrystalline, macrocrystalline, and architectural. The studies were based on laser coherent polarimetry ensuring the retrieval of the fullest information about the optical and polarisation properties of bone tissue. A method was developed for contactless noninvasive diagnostics of the orientational and mineralogical structure of bone tissue considered as a biofractal.

Modelling the temperature evolution of bone under high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

ten Eikelder, H. M. M.; Bošnački, D.; Elevelt, A.; Donato, K.; Di Tullio, A.; Breuer, B. J. T.; van Wijk, J. H.; van Dijk, E. V. M.; Modena, D.; Yeo, S. Y.; Grüll, H.

2016-02-01

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR-HIFU treatments.

Predicting bone strength with ultrasonic guided waves

PubMed Central

Bochud, Nicolas; Vallet, Quentin; Minonzio, Jean-Gabriel; Laugier, Pascal

2017-01-01

Recent bone quantitative ultrasound approaches exploit the multimode waveguide response of long bones for assessing properties such as cortical thickness and stiffness. Clinical applications remain, however, challenging, as the impact of soft tissue on guided waves characteristics is not fully understood yet. In particular, it must be clarified whether soft tissue must be incorporated in waveguide models needed to infer reliable cortical bone properties. We hypothesize that an inverse procedure using a free plate model can be applied to retrieve the thickness and stiffness of cortical bone from experimental data. This approach is first validated on a series of laboratory-controlled measurements performed on assemblies of bone- and soft tissue mimicking phantoms and then on in vivo measurements. The accuracy of the estimates is evaluated by comparison with reference values. To further support our hypothesis, these estimates are subsequently inserted into a bilayer model to test its accuracy. Our results show that the free plate model allows retrieving reliable waveguide properties, despite the presence of soft tissue. They also suggest that the more sophisticated bilayer model, although it is more precise to predict experimental data in the forward problem, could turn out to be hardly manageable for solving the inverse problem. PMID:28256568

Practical Modeling Concepts for Connective Tissue Stem Cell and Progenitor Compartment Kinetics

PubMed Central

2003-01-01

Stem cell activation and development is central to skeletal development, maintenance, and repair, as it is for all tissues. However, an integrated model of stem cell proliferation, differentiation, and transit between functional compartments has yet to evolve. In this paper, the authors review current concepts in stem cell biology and progenitor cell growth and differentiation kinetics in the context of bone formation. A cell-based modeling strategy is developed and offered as a tool for conceptual and quantitative exploration of the key kinetic variables and possible organizational hierarchies in bone tissue development and remodeling, as well as in tissue engineering strategies for bone repair. PMID:12975533

Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone.

PubMed

Akar, Banu; Tatara, Alexander M; Sutradhar, Alok; Hsiao, Hui-Yi; Miller, Michael; Cheng, Ming-Huei; Mikos, Antonios G; Brey, Eric M

2018-04-12

Reconstruction of large skeletal defects is challenging due to the requirement for large volumes of donor tissue and the often complex surgical procedures. Tissue engineering has the potential to serve as a new source of tissue for bone reconstruction, but current techniques are often limited in regards to the size and complexity of tissue that can be formed. Building tissue using an in vivo bioreactor approach may enable the production of appropriate amounts of specialized tissue, while reducing issues of donor site morbidity and infection. Large animals are required to screen and optimize new strategies for growing clinically appropriate volumes of tissues in vivo. In this article, we review both ovine and porcine models that serve as models of the technique proposed for clinical engineering of bone tissue in vivo. Recent findings are discussed with these systems, as well as description of next steps required for using these models, to develop clinically applicable tissue engineering applications.

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

Bioelectric modulation of wound healing in a 3D in vitro model of tissue-engineered bone.

PubMed

Sundelacruz, Sarah; Li, Chunmei; Choi, Young Jun; Levin, Michael; Kaplan, David L

2013-09-01

Long-standing interest in bioelectric regulation of bone fracture healing has primarily focused on exogenous stimulation of bone using applied electromagnetic fields. Endogenous electric signals, such as spatial gradients of resting potential among non-excitable cells in vivo, have also been shown to be important in cell proliferation, differentiation, migration, and tissue regeneration, and may therefore have as-yet unexplored therapeutic potential for regulating wound healing in bone tissue. To study this form of bioelectric regulation, there is a need for three-dimensional (3D) in vitro wound tissue models that can overcome limitations of current in vivo models. We present a 3D wound healing model in engineered bone tissue that serves as a pre-clinical experimental platform for studying electrophysiological regulation of wound healing. Using this system, we identified two electrophysiology-modulating compounds, glibenclamide and monensin, that augmented osteoblast mineralization. Of particular interest, these compounds displayed differential effects in the wound area compared to the surrounding tissue. Several hypotheses are proposed to account for these observations, including the existence of heterogeneous subpopulations of osteoblasts that respond differently to bioelectric signals, or the capacity of the wound-specific biochemical and biomechanical environment to alter cell responses to electrophysiological treatments. These data indicate that a comprehensive characterization of the cellular, biochemical, biomechanical, and bioelectrical components of in vitro wound models is needed to develop bioelectric strategies to control cell functions for improved bone regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mechanical loading, damping, and load-driven bone formation in mouse tibiae.

PubMed

Dodge, Todd; Wanis, Mina; Ayoub, Ramez; Zhao, Liming; Watts, Nelson B; Bhattacharya, Amit; Akkus, Ozan; Robling, Alexander; Yokota, Hiroki

2012-10-01

Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone's compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. Copyright © 2012 Elsevier Inc. All rights reserved.

Top down and bottom up engineering of bone.

PubMed

Knothe Tate, Melissa L

2011-01-11

The goal of this retrospective article is to place the body of my lab's multiscale mechanobiology work in context of top-down and bottom-up engineering of bone. We have used biosystems engineering, computational modeling and novel experimental approaches to understand bone physiology, in health and disease, and across time (in utero, postnatal growth, maturity, aging and death, as well as evolution) and length scales (a single bone like a femur, m; a sample of bone tissue, mm-cm; a cell and its local environment, μm; down to the length scale of the cell's own skeleton, the cytoskeleton, nm). First we introduce the concept of flow in bone and the three calibers of porosity through which fluid flows. Then we describe, in the context of organ-tissue, tissue-cell and cell-molecule length scales, both multiscale computational models and experimental methods to predict flow in bone and to understand the flow of fluid as a means to deliver chemical and mechanical cues in bone. Addressing a number of studies in the context of multiple length and time scales, the importance of appropriate boundary conditions, site specific material parameters, permeability measures and even micro-nanoanatomically correct geometries are discussed in context of model predictions and their value for understanding multiscale mechanobiology of bone. Insights from these multiscale computational modeling and experimental methods are providing us with a means to predict, engineer and manufacture bone tissue in the laboratory and in the human body. Copyright © 2010 Elsevier Ltd. All rights reserved.

Soft Tissue Alterations in Esthetic Postextraction Sites: A 3-Dimensional Analysis.

PubMed

Chappuis, V; Engel, O; Shahim, K; Reyes, M; Katsaros, C; Buser, D

2015-09-01

Dimensional alterations of the facial soft and bone tissues following tooth extraction in the esthetic zone play an essential role to achieve successful outcomes in implant therapy. This prospective study is the first to investigate the interplay between the soft tissue dimensions and the underlying bone anatomy during an 8-wk healing period. The analysis is based on sequential 3-dimensional digital surface model superimpositions of the soft and bone tissues using digital impressions and cone beam computed tomography during an 8-wk healing period. Soft tissue thickness in thin and thick bone phenotypes at extraction was similar, averaging 0.7 mm and 0.8 mm, respectively. Interestingly, thin bone phenotypes revealed a 7-fold increase in soft tissue thickness after an 8-wk healing period, whereas in thick bone phenotypes, the soft tissue dimensions remained unchanged. The observed spontaneous soft tissue thickening in thin bone phenotypes resulted in a vertical soft tissue loss of only 1.6 mm, which concealed the underlying vertical bone resorption of 7.5 mm. Because of spontaneous soft tissue thickening, no significant differences were detected in the total tissue loss between thin and thick bone phenotypes at 2, 4, 6, and 8 wk. More than 51% of these dimensional alterations occurred within 2 wk of healing. Even though the observed spontaneous soft tissue thickening in thin bone phenotypes following tooth extraction conceals the pronounced underlying bone resorption pattern by masking the true bone deficiency, spontaneous soft tissue thickening offers advantages for subsequent bone regeneration and implant therapies in sites with high esthetic demand (Clinicaltrials.gov NCT02403700). © International & American Associations for Dental Research.

Textural versus electrostatic exclusion-enrichment effects in the effective chemical transport within the cortical bone: a numerical investigation.

PubMed

Lemaire, T; Kaiser, J; Naili, S; Sansalone, V

2013-11-01

Interstitial fluid within bone tissue is known to govern the remodelling signals' expression. Bone fluid flow is generated by skeleton deformation during the daily activities. Due to the presence of charged surfaces in the bone porous matrix, the electrochemical phenomena occurring in the vicinity of mechanosensitive bone cells, the osteocytes, are key elements in the cellular communication. In this study, a multiscale model of interstitial fluid transport within bone tissues is proposed. Based on an asymptotic homogenization method, our modelling takes into account the physicochemical properties of bone tissue. Thanks to this multiphysical approach, the transport of nutrients and waste between the blood vessels and the bone cells can be quantified to better understand the mechanotransduction of bone remodelling. In particular, it is shown that the electrochemical tortuosity may have stronger implications in the mass transport within the bone than the purely morphological one. Copyright © 2013 John Wiley & Sons, Ltd.

Powder-based 3D printing for bone tissue engineering.

PubMed

Brunello, G; Sivolella, S; Meneghello, R; Ferroni, L; Gardin, C; Piattelli, A; Zavan, B; Bressan, E

2016-01-01

Bone tissue engineered 3-D constructs customized to patient-specific needs are emerging as attractive biomimetic scaffolds to enhance bone cell and tissue growth and differentiation. The article outlines the features of the most common additive manufacturing technologies (3D printing, stereolithography, fused deposition modeling, and selective laser sintering) used to fabricate bone tissue engineering scaffolds. It concentrates, in particular, on the current state of knowledge concerning powder-based 3D printing, including a description of the properties of powders and binder solutions, the critical phases of scaffold manufacturing, and its applications in bone tissue engineering. Clinical aspects and future applications are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2

PubMed Central

2015-01-01

The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2) has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies. PMID:26043112

[Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

PubMed

Wei, Xuelei; Dong, Fuhui

2011-12-01

To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

Modelling the mechanics of partially mineralized collagen fibrils, fibres and tissue

PubMed Central

Liu, Yanxin; Thomopoulos, Stavros; Chen, Changqing; Birman, Victor; Buehler, Markus J.; Genin, Guy M.

2014-01-01

Progressive stiffening of collagen tissue by bioapatite mineral is important physiologically, but the details of this stiffening are uncertain. Unresolved questions about the details of the accommodation of bioapatite within and upon collagen's hierarchical structure have posed a central hurdle, but recent microscopy data resolve several major questions. These data suggest how collagen accommodates bioapatite at the lowest relevant hierarchical level (collagen fibrils), and suggest several possibilities for the progressive accommodation of bioapatite at higher hierarchical length scales (fibres and tissue). We developed approximations for the stiffening of collagen across spatial hierarchies based upon these data, and connected models across hierarchies levels to estimate mineralization-dependent tissue-level mechanics. In the five possible sequences of mineralization studied, percolation of the bioapatite phase proved to be an important determinant of the degree of stiffening by bioapatite. The models were applied to study one important instance of partially mineralized tissue, which occurs at the attachment of tendon to bone. All sequences of mineralization considered reproduced experimental observations of a region of tissue between tendon and bone that is more compliant than either tendon or bone, but the size and nature of this region depended strongly upon the sequence of mineralization. These models and observations have implications for engineered tissue scaffolds at the attachment of tendon to bone, bone development and graded biomimetic attachment of dissimilar hierarchical materials in general. PMID:24352669

Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

PubMed Central

Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

2013-01-01

Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. The expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization, and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and fibronectin 1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry, and neurological disease, and fibronectin 1 is involved in cellular assembly, organization, and maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and they provide novel insight into the molecular mechanisms involved in the healing of periodontal tissue after tooth extraction. PMID:23824910

Ultraviolet-C irradiation to titanium implants increases peri-implant bone formation without impeding mineralization in a rabbit femur model.

PubMed

Yamazaki, Makoto; Yamada, Masahiro; Ishizaki, Ken; Sakurai, Kaoru

2015-05-01

Volume and bone quality of peri-implant supporting bone, in particular, at implant neck region, as well as bone-implant contact ratio, is important for long-term stability of implants. Ultraviolet-C (UVC) irradiation is known to enhance the osseointegration capability of titanium implants. However, the histological determination was performed only on a rat model, but not pre-clinical animal model such as a rabbit model. The purpose of this study was to determine the effects of UVC irradiation on titanium implants on the volume and mineral density of peri-implant supporting bone formation in a rabbit femur model. Acid-etched pure titanium screw implants with or without 3 mW/cm2 UVC irradiation for 48 h were placed in rabbit femur diaphyses. Peri-implant bone tissue formation was analyzed at 3 and 8 weeks post-operatively by histology and micro-CT-based bone morphometry after calibration with hydroxyl apatite phantoms. UVC pre-irradiated implants accumulated a higher density of cells and thicker and longer bone tissue attachments that continued into the inner basic lamellae of the surface of existing cortical bone at 3 and 8 weeks than the implants without irradiation. Although the bone mineral density around both implants was equivalent to that of the existing cortical bone, bone volume was greater with UVC pre-irradiation in two-thirds or more of the apical region throughout the observation period. These results indicate that UVC treatment increased the volume of cortical-like bone tissue in the coronal region of titanium implants without deterioration of bone mineral density.

A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus.

PubMed

Mansur, Sity Aishah; Mieczkowska, Aleksandra; Flatt, Peter R; Bouvard, Beatrice; Chappard, Daniel; Irwin, Nigel; Mabilleau, Guillaume

2016-06-01

Obesity and type 2 diabetes mellitus (T2DM) progress worldwide with detrimental effects on several physiological systems including bone tissue mainly by affecting bone quality. Several gut hormones analogues have been proven potent in ameliorating bone quality. In the present study, we used the leptin receptor-deficient db/db mice as a model of obesity and severe T2DM to assess the extent of bone quality alterations at the organ and tissue levels. We also examined the beneficial effects of gut hormone therapy in this model by using a new triple agonist ([d-Ala(2)]GIP-Oxm) active at the GIP, GLP-1 and glucagon receptors. As expected, db/db mice presented with dramatic alterations of bone strength at the organ level associated with deterioration of trabecular and cortical microarchitectures and an augmentation in osteoclast numbers. At the tissue level, these animals presented also with alterations of bone strength (reduced hardness, indentation modulus and dissipated energy) with modifications of tissue mineral distribution, collagen glycation and collagen maturity. The use of [d-Ala(2)]GIP-Oxm considerably improved bone strength at the organ level with modest effects on trabecular microarchitecture. At the tissue level, [d-Ala(2)]GIP-Oxm ameliorated bone strength reductions with positive effects on collagen glycation and collagen maturity. This study provides support for including gut hormone analogues as possible new therapeutic strategies for improving bone quality in bone complications associated to T2DM. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of bar cross-section geometry on stress distribution in overdenture-retaining system simulating horizontal misfit and bone loss.

PubMed

Spazzin, Aloísio Oro; Costa, Ana Rosa; Correr, Américo Bortolazzo; Consani, Rafael Leonardo Xediek; Correr-Sobrinho, Lourenço; dos Santos, Mateus Bertolini Fernandes

2013-08-09

This study evaluated the influence of cross-section geometry of the bar framework on the distribution of static stresses in an overdenture-retaining bar system simulating horizontal misfit and bone loss. Three-dimensional FE models were created including two titanium implants and three cross-section geometries (circular, ovoid or Hader) of bar framework placed in the anterior part of a severely resorbed jaw. One model with 1.4-mm vertical loss of the peri-implant tissue was also created. The models set were exported to mechanical simulation software, where horizontal displacement (10, 50 or 100 μm) was applied simulating the settling of the framework, which suffered shrinkage during the laboratory procedures. The bar material used for the bar framework was a cobalt--chromium alloy. For evaluation of bone loss effect, only the 50-μm horizontal misfit was simulated. Data were qualitatively and quantitatively evaluated using von Mises stress for the mechanical part and maximum principal stress and μ-strain for peri-implant bone tissue given by the software. Stresses were concentrated along the bar and in the join between the bar and cylinder. In the peri-implant bone tissue, the μ-strain was higher in the cervical third. Higher stress levels and μ-strain were found for the models using the Hader bar. The bone loss simulated presented considerable increase on maximum principal stresses and μ-strain in the peri-implant bone tissue. In addition, for the amplification of the horizontal misfit, the higher complexity of the bar cross-section geometry and bone loss increases the levels of static stresses in the peri-implant bone tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

Theoretical Bounds for the Influence of Tissue-Level Ductility on the Apparent-Level Strength of Human Trabecular Bone

PubMed Central

Nawathe, Shashank; Juillard, Frédéric; Keaveny, Tony M.

2015-01-01

The role of tissue-level post-yield behavior on the apparent-level strength of trabecular bone is a potentially important aspect of bone quality. To gain insight into this issue, we compared the apparent-level strength of trabecular bone for the hypothetical cases of fully brittle versus fully ductile failure behavior of the trabecular tissue. Twenty human cadaver trabecular bone specimens (5 mm cube; BV/TV = 6–36%) were scanned with micro-CT to create 3D finite element models (22-micron element size). For each model, apparent-level strength was computed assuming either fully brittle (fracture with no tissue ductility) or fully ductile (yield with no tissue fracture) tissue-level behaviors. We found that the apparent-level ultimate strength for the brittle behavior was only about half the value of the apparent-level 0.2%-offset yield strength for the ductile behavior, and the ratio of these brittle to ductile strengths was almost constant (mean ± SD = 0.56 ± 0.02; n=20; R2 = 0.99 between the two measures). As a result of this small variation, although the ratio of brittle to ductile strengths was positively correlated with the bone volume fraction (R2=0.44, p=0.01) and structure model index (SMI, R2=0.58, p<0.01), these effects were small. Mechanistically, the fully ductile behavior resulted in a much higher apparent-level strength because in this case about 16-fold more tissue was required to fail than for the fully brittle behavior; also, there was more tensile- than compressive-mode of failure at the tissue level for the fully brittle behavior. We conclude that, in theory, the apparent-level strength behavior of human trabecular bone can vary appreciably depending on whether the tissue fails in a fully ductile versus fully brittle manner, and this effect is largely constant despite appreciable variations in bone volume fraction and microarchitecture. PMID:23497799

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 use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering.

PubMed

Wang, Zhong-Shan; Feng, Zhi-Hong; Wu, Guo-Feng; Bai, Shi-Zhu; Dong, Yan; Chen, Fa-Ming; Zhao, Yi-Min

2016-06-21

Periodontal regeneration involves the restoration of at least three unique tissues: cementum, periodontal ligament tissue (PDL) and alveolar bone tissue. Here, we first isolated human PDL stem cells (PDLSCs) and jaw bone mesenchymal stem cells (JBMSCs). These cells were then induced to form cell sheets using an ascorbic acid-rich approach, and the cell sheet properties, including morphology, thickness and gene expression profile, were compared. Platelet-rich fibrin (PRF) derived from human venous blood was then fabricated into bioabsorbable fibrin scaffolds containing various growth factors. Finally, the in vivo potential of a cell-material construct based on PDLSC sheets, PRF scaffolds and JBMSC sheets to form periodontal tissue was assessed in a nude mouse model. In this model, PDLSC sheet/PRF/JBMSC sheet composites were placed in a simulated periodontal space comprising human treated dentin matrix (TDM) and hydroxyapatite (HA)/tricalcium phosphate (TCP) frameworks. Eight weeks after implantation, the PDLSC sheets tended to develop into PDL-like tissues, while the JBMSC sheets tended to produce predominantly bone-like tissues. In addition, the PDLSC sheet/PRF/JBMSC sheet composites generated periodontal tissue-like structures containing PDL- and bone-like tissues. Further improvements in this cell transplantation design may have the potential to provide an effective approach for future periodontal tissue regeneration.

Pharmacokinetic Models for the Elimination of Drinking Water Contaminants from the Body,

DTIC Science & Technology

1990-03-01

that are sequestered in the bones (lead, barium), in certain soft tissues such as the kidney ( cadmium ), and in the adipose tissue (DDT...slow" component (sequestered in 3 bone or in adipose tissue ). Finally, much more attention must be given to differences among I individuals and among...lead from bone, effectively reducing the half-life. Fasting or starvation can mobilize toxicants 3 stored in adipose tissue . Competition for enzyme

Systematic evaluation of a tissue-engineered bone for maxillary sinus augmentation in large animal canine model.

PubMed

Wang, Shaoyi; Zhang, Zhiyuan; Xia, Lunguo; Zhao, Jun; Sun, Xiaojuan; Zhang, Xiuli; Ye, Dongxia; Uludağ, Hasan; Jiang, Xinquan

2010-01-01

The objective of this study is to systematically evaluate the effects of a tissue-engineered bone complex for maxillary sinus augmentation in a canine model. Twelve sinus floor augmentation surgeries in 6 animals were performed bilaterally and randomly repaired with the following 3 groups of grafts: group A consisted of tissue-engineered osteoblasts/beta-TCP complex (n=4); group B consisted of beta-TCP alone (n=4); group C consisted of autogenous bone obtained from iliac crest as a positive control (n=4). All dogs had uneventful healings following the surgery. Sequential polychrome fluorescent labeling, maxillofacial CT, microhardness tests, as well as histological and histomorphometric analyses indicated that the tissue-engineered osteoblasts/beta-TCP complex dramatically promoted bone formation and mineralization and maximally maintained the height and volume of elevated maxillary sinus. By comparison, both control groups of beta-TCP or autologous iliac bone showed considerable resorption and replacement by fibrous or fatty tissue. We thus conclude that beta-TCP alone could barely maintain the height and volume of the elevated sinus floor, and that the transplantation of autogenous osteoblasts on beta-TCP could promote earlier bone formation and mineralization, maximally maintain height, volume and increase the compressive strength of augmented maxillary sinus. This tissue engineered bone complex might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Numerical investigation of bone remodelling around immediately loaded dental implants using sika deer (Cervus nippon) antlers as implant bed.

PubMed

He, Yun; Hasan, Istabrak; Keilig, Ludger; Fischer, Dominik; Ziegler, Luisa; Abboud, Marcus; Wahl, Gerhard; Bourauel, Christoph

2018-03-01

This study combines finite element method and animal studies, aiming to investigate tissue remodelling processes around dental implants inserted into sika deer antler and to develop an alternative animal consuming model for studying bone remodelling around implants. Implants were inserted in the antlers and loaded immediately via a self-developed loading device. After 3, 4, 5 and 6 weeks, implants and surrounding tissue were taken out. Specimens were scanned by μCT scanner and finite element models were generated. Immediate loading and osseointegration conditions were simulated at the implant-tissue interface. A vertical force of 10 N was applied on the implant. During the healing time, density and Young's modulus of antler tissue around the implant increased significantly. For each time point, the values of displacement, stresses and strains in the osseointegration model were lower than those of the immediate loading model. As the healing time increased, the displacement of implants was reduced. The 3-week immediate loading model (9878 ± 1965 μstrain) illustrated the highest strains in the antler tissue. Antler tissue showed similar biomechanical properties as human bone in investigating the bone remodelling around implants, therefore the use of sika deer antler model is a promising alternative in implant biomechanical studies.

New description of gradual substitution of graft by bone tissue including biomechanical and structural effects, nutrients supply and consumption

NASA Astrophysics Data System (ADS)

Lu, Yanfei; Lekszycki, Tomasz

2018-03-01

A new description of graft substitution by bone tissue is proposed in this work. The studied domain is considered as a continuum model consisting of a mixture of the bone tissue and the graft material. Densities of both components evolve in time as a result of cellular activity and biodegradation. The proposed model focuses on the interaction between the bone cell activity, mechanical stimuli, nutrients supply and scaffold microstructure. Different combinations of degradation rate and stiffness of the graft material were examined by numerical simulation. It follows from the calculations that the degradation rate of the scaffold should be tuned to the synthesis/resorption rate of the tissue, which are dependent among the others on scaffold porosity changes. Simulation results imply potential criteria to choose proper bone substitute material in consideration of degradation rate, initial porosity and mechanical characteristics.

Elastic properties of a porous titanium-bone tissue composite.

PubMed

Rubshtein, A P; Makarova, E B; Rinkevich, A B; Medvedeva, D S; Yakovenkova, L I; Vladimirov, A B

2015-01-01

The porous titanium implants were introduced into the condyles of tibias and femurs of sheep. New bone tissue fills the pore, and the porous titanium-new bone tissue composite is formed. The duration of composite formation was 4, 8, 24 and 52 weeks. The formed composites were extracted from the bone and subjected to a compression test. The Young's modulus was calculated using the measured stress-strain curve. The time dependence of the Young's modulus of the composite was obtained. After 4 weeks the new bone tissue that filled the pores does not affect the elastic properties of implants. After 24 and 52 weeks the Young's modulus increases by 21-34% and 62-136%, respectively. The numerical calculations of the elasticity of porous titanium-new bone tissue composite were conducted using a simple polydisperse model that is based on the consideration of heterogeneous structure as a continuous medium with spherical inclusions of different sizes. The kinetics of the change in the elasticity of the new bone tissue is presented via the intermediate characteristics, namely the relative ultimate tensile strength or proportion of mature bone tissue in the bone tissue. The calculated and experimentally measured values of the Young's modulus of the composite are in good agreement after 8 weeks of composite formation. The properties of the porous titanium-new bone tissue composites can only be predicted when data on the properties of new bone tissue are available after 8 weeks of contact between the implant and the native bone. Copyright © 2015 Elsevier B.V. All rights reserved.

Theoretical effects of fully ductile versus fully brittle behaviors of bone tissue on the strength of the human proximal femur and vertebral body.

PubMed

Nawathe, Shashank; Yang, Haisheng; Fields, Aaron J; Bouxsein, Mary L; Keaveny, Tony M

2015-05-01

The influence of the ductility of bone tissue on whole-bone strength represents a fundamental issue of multi-scale biomechanics. To gain insight, we performed a computational study of 16 human proximal femurs and 12 T9 vertebral bodies, comparing the whole-bone strength for the two hypothetical bounding cases of fully brittle versus fully ductile tissue-level failure behaviors, all other factors, including tissue-level elastic modulus and yield stress, held fixed. For each bone, a finite element model was generated (60-82 μm element size; up to 120 million elements) and was virtually loaded in habitual (stance for femur, compression for vertebra) and non-habitual (sideways fall, only for femur) loading modes. Using a geometrically and materially non-linear model, the tissue was assumed to be either fully brittle or fully ductile. We found that, under habitual loading, changing the tissue behavior from fully ductile to fully brittle reduced whole-bone strength by 38.3±2.4% (mean±SD) and 39.4±1.9% for the femur and vertebra, respectively (p=0.39 for site difference). These reductions were remarkably uniform across bones, but (for the femur) were greater for non-habitual (57.1±4.7%) than habitual loading (p<0.001). At overall structural failure, there was 5-10-fold less failed tissue for the fully brittle than fully ductile cases. These theoretical results suggest that the whole-bone strength of the proximal femur and vertebra can vary substantially between fully brittle and fully ductile tissue-level behaviors, an effect that is relatively insensitive to bone morphology but greater for non-habitual loading. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vivo outcomes of tissue-engineered osteochondral grafts.

PubMed

Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

2010-04-01

Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

Numerical simulation of electrically stimulated osteogenesis in dental implants.

PubMed

Vanegas-Acosta, J C; Garzón-Alvarado, D A; Lancellotti, V

2014-04-01

Cell behavior and tissue formation are influenced by a static electric field (EF). Several protocols for EF exposure are aimed at increasing the rate of tissue recovery and reducing the healing times in wounds. However, the underlying mechanisms of the EF action on cells and tissues are still a matter of research. In this work we introduce a mathematical model for electrically stimulated osteogenesis at the bone-dental implant interface. The model describes the influence of the EF in the most critical biological processes leading to bone formation at the bone-dental implant interface. The numerical solution is able to reproduce the distribution of spatial-temporal patterns describing the influence of EF during blood clotting, osteogenic cell migration, granulation tissue formation, displacements of the fibrillar matrix, and formation of new bone. In addition, the model describes the EF-mediated cell behavior and tissue formation which lead to an increased osteogenesis in both smooth and rough implant surfaces. Since numerical results compare favorably with experimental evidence, the model can be used to predict the outcome of using electrostimulation in other types of wounds and tissues. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies

PubMed Central

Caballero, Montserrat; Morse, Justin C.; Halevi, Alexandra E.; Emodi, Omri; Pharaon, Michael R.; Wood, Jeyhan S.

2015-01-01

Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect. PMID:25837453

Finite Element-Based Mechanical Assessment of Bone Quality on the Basis of In Vivo Images.

PubMed

Pahr, Dieter H; Zysset, Philippe K

2016-12-01

Beyond bone mineral density (BMD), bone quality designates the mechanical integrity of bone tissue. In vivo images based on X-ray attenuation, such as CT reconstructions, provide size, shape, and local BMD distribution and may be exploited as input for finite element analysis (FEA) to assess bone fragility. Further key input parameters of FEA are the material properties of bone tissue. This review discusses the main determinants of bone mechanical properties and emphasizes the added value, as well as the important assumptions underlying finite element analysis. Bone tissue is a sophisticated, multiscale composite material that undergoes remodeling but exhibits a rather narrow band of tissue mineralization. Mechanically, bone tissue behaves elastically under physiologic loads and yields by cracking beyond critical strain levels. Through adequate cell-orchestrated modeling, trabecular bone tunes its mechanical properties by volume fraction and fabric. With proper calibration, these mechanical properties may be incorporated in quantitative CT-based finite element analysis that has been validated extensively with ex vivo experiments and has been applied increasingly in clinical trials to assess treatment efficacy against osteoporosis.

Biomimetic stratified scaffold design for ligament-to-bone interface tissue engineering.

PubMed

Lu, Helen H; Spalazzi, Jeffrey P

2009-07-01

The emphasis in the field of orthopaedic tissue engineering is on imparting biomimetic functionality to tissue engineered bone or soft tissue grafts and enabling their translation to the clinic. A significant challenge in achieving extended graft functionality is engineering the biological fixation of these grafts with each other as well as with the host environment. Biological fixation will require re-establishment of the structure-function relationship inherent at the native soft tissue-to-bone interface on these tissue engineered grafts. To this end, strategic biomimicry must be incorporated into advanced scaffold design. To facilitate integration between distinct tissue types (e.g., bone with soft tissues such as cartilage, ligament, or tendon), a stratified or multi-phasic scaffold with distinct yet continuous tissue regions is required to pre-engineer the interface between bone and soft tissues. Using the ACL-to-bone interface as a model system, this review outlines the strategies for stratified scaffold design for interface tissue engineering, focusing on identifying the relevant design parameters derived from an understanding of the structure-function relationship inherent at the soft-to-hard tissue interface. The design approach centers on first addressing the challenge of soft tissue-to-bone integration ex vivo, and then subsequently focusing on the relatively less difficult task of bone-to-bone integration in vivo. In addition, we will review stratified scaffold design aimed at exercising spatial control over heterotypic cellular interactions, which are critical for facilitating the formation and maintenance of distinct yet continuous multi-tissue regions. Finally, potential challenges and future directions in this emerging area of advanced scaffold design will be discussed.

Hard tissue as a composite material. I - Bounds on the elastic behavior.

NASA Technical Reports Server (NTRS)

Katz, J. L.

1971-01-01

Recent determination of the elastic moduli of hydroxyapatite by ultrasonic methods permits a re-examination of the Voigt or parallel model of the elastic behavior of bone, as a two phase composite material. It is shown that such a model alone cannot be used to describe the behavior of bone. Correlative data on the elastic moduli of dentin, enamel and various bone samples indicate the existence of a nonlinear dependence of elastic moduli on composition of hard tissue. Several composite models are used to calculate the bounds on the elastic behavior of these tissues. The limitations of these models are described, and experiments to obtain additional critical data are discussed.

Micromechanical modeling of elastic properties of cortical bone accounting for anisotropy of dense tissue.

PubMed

Salguero, Laura; Saadat, Fatemeh; Sevostianov, Igor

2014-10-17

The paper analyzes the connection between microstructure of the osteonal cortical bone and its overall elastic properties. The existing models either neglect anisotropy of the dense tissue or simplify cortical bone microstructure (accounting for Haversian canals only). These simplifications (related mostly to insufficient mathematical apparatus) complicate quantitative analysis of the effect of microstructural changes - produced by age, microgravity, or some diseases - on the overall mechanical performance of cortical bone. The present analysis fills this gap; it accounts for anisotropy of the dense tissue and uses realistic model of the porous microstructure. The approach is based on recent results of Sevostianov et al. (2005) and Saadat et al. (2012) on inhomogeneities in a transversely-isotropic material. Bone's microstructure is modeled according to books of Martin and Burr (1989), Currey (2002), and Fung (1993) and includes four main families of pores. The calculated elastic constants for porous cortical bone are in agreement with available experimental data. The influence of each of the pore types on the overall moduli is examined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: a better model.

PubMed

Dong, Qing-shan; Shang, Hong-tao; Wu, Wei; Chen, Fu-lin; Zhang, Jun-rui; Guo, Jia-ping; Mao, Tian-qiu

2012-08-01

The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone. Copyright © 2012 Elsevier B.V. All rights reserved.

Pseudofracture: an acute peripheral tissue trauma model.

PubMed

Darwiche, Sophie S; Kobbe, Philipp; Pfeifer, Roman; Kohut, Lauryn; Pape, Hans-Christoph; Billiar, Timothy

2011-04-18

Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality. Many studies have begun to assess these changes in the reactivity of the immune system following trauma. Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses. The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone. The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age- and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution. Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the pseudofracture, as we wanted a sterile yet proportionally severe peripheral tissue trauma model. Hemorrhagic shock is a common finding in the setting of severe trauma, and the global hypoperfusion adds a very relevant element to a trauma model. The pseudofracture model can be easily combined with a hemorrhagic shock model for a multiple trauma model of high severity.

An image-based skeletal dosimetry model for the ICRP reference newborn—internal electron sources

NASA Astrophysics Data System (ADS)

Pafundi, Deanna; Rajon, Didier; Jokisch, Derek; Lee, Choonsik; Bolch, Wesley

2010-04-01

In this study, a comprehensive electron dosimetry model of newborn skeletal tissues is presented. The model is constructed using the University of Florida newborn hybrid phantom of Lee et al (2007 Phys. Med. Biol. 52 3309-33), the newborn skeletal tissue model of Pafundi et al (2009 Phys. Med. Biol. 54 4497-531) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow (surrogate tissue for hematopoietic stem cells), shallow marrow (surrogate tissue for osteoprogenitor cells) and unossified cartilage (surrogate tissue for chondrocytes). Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following source tissues: active marrow, trabecular bone (surfaces and volumes), cortical bone (surfaces and volumes) and cartilage. Transport results are reported as specific absorbed fractions according to the MIRD schema and are given as skeletal-averaged values in the paper with bone-specific values reported in both tabular and graphic format as electronic annexes (supplementary data). The method utilized in this work uniquely includes (1) explicit accounting for the finite size and shape of newborn ossification centers (spongiosa regions), (2) explicit accounting for active and shallow marrow dose from electron emissions in cortical bone as well as sites of unossified cartilage, (3) proper accounting of the distribution of trabecular and cortical volumes and surfaces in the newborn skeleton when considering mineral bone sources and (4) explicit consideration of the marrow cellularity changes for active marrow self-irradiation as applicable to radionuclide therapy of diseased marrow in the newborn child.

Patient-specific in silico models can quantify primary implant stability in elderly human bone.

PubMed

Steiner, Juri A; Hofmann, Urs A T; Christen, Patrik; Favre, Jean M; Ferguson, Stephen J; van Lenthe, G Harry

2018-03-01

Secure implant fixation is challenging in osteoporotic bone. Due to the high variability in inter- and intra-patient bone quality, ex vivo mechanical testing of implants in bone is very material- and time-consuming. Alternatively, in silico models could substantially reduce costs and speed up the design of novel implants if they had the capability to capture the intricate bone microstructure. Therefore, the aim of this study was to validate a micro-finite element model of a multi-screw fracture fixation system. Eight human cadaveric humerii were scanned using micro-CT and mechanically tested to quantify bone stiffness. Osteotomy and fracture fixation were performed, followed by mechanical testing to quantify displacements at 12 different locations on the instrumented bone. For each experimental case, a micro-finite element model was created. From the micro-finite element analyses of the intact model, the patient-specific bone tissue modulus was determined such that the simulated apparent stiffness matched the measured stiffness of the intact bone. Similarly, the tissue modulus of a small damage region around each screw was determined for the instrumented bone. For validation, all in silico models were rerun using averaged material properties, resulting in an average coefficient of determination of 0.89 ± 0.04 with a slope of 0.93 ± 0.19 and a mean absolute error of 43 ± 10 μm when correlating in silico marker displacements with the ex vivo test. In conclusion, we validated a patient-specific computer model of an entire organ bone-implant system at the tissue-level at high resolution with excellent overall accuracy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:954-962, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering

PubMed Central

Wang, Zhong-Shan; Feng, Zhi-Hong; Wu, Guo-Feng; Bai, Shi-Zhu; Dong, Yan; Chen, Fa-Ming; Zhao, Yi-Min

2016-01-01

Periodontal regeneration involves the restoration of at least three unique tissues: cementum, periodontal ligament tissue (PDL) and alveolar bone tissue. Here, we first isolated human PDL stem cells (PDLSCs) and jaw bone mesenchymal stem cells (JBMSCs). These cells were then induced to form cell sheets using an ascorbic acid-rich approach, and the cell sheet properties, including morphology, thickness and gene expression profile, were compared. Platelet-rich fibrin (PRF) derived from human venous blood was then fabricated into bioabsorbable fibrin scaffolds containing various growth factors. Finally, the in vivo potential of a cell-material construct based on PDLSC sheets, PRF scaffolds and JBMSC sheets to form periodontal tissue was assessed in a nude mouse model. In this model, PDLSC sheet/PRF/JBMSC sheet composites were placed in a simulated periodontal space comprising human treated dentin matrix (TDM) and hydroxyapatite (HA)/tricalcium phosphate (TCP) frameworks. Eight weeks after implantation, the PDLSC sheets tended to develop into PDL-like tissues, while the JBMSC sheets tended to produce predominantly bone-like tissues. In addition, the PDLSC sheet/PRF/JBMSC sheet composites generated periodontal tissue-like structures containing PDL- and bone-like tissues. Further improvements in this cell transplantation design may have the potential to provide an effective approach for future periodontal tissue regeneration. PMID:27324079

Simulation of peri-implant bone healing due to immediate loading in dental implant treatments.

PubMed

Chou, Hsuan-Yu; Müftü, Sinan

2013-03-15

The goal of this work was to investigate the role of immediate loading on the peri-implant bone healing in dental implant treatments. A mechano-regulatory tissue differentiation model that takes into account the stimuli through the solid and the fluid components of the healing tissue, and the diffusion of pluripotent stem cells into the healing callus was used. A two-dimensional axisymmetric model consisting of a dental implant, the healing callus tissue and the host bone tissue was constructed for the finite element analysis. Poroelastic material properties were assigned to the healing callus and the bone tissue. The effects of micro-motion, healing callus size, and implant thread design on the length of the bone-to-implant contact (BIC) and the bone volume (BV) formed in the healing callus were investigated. In general, the analysis predicted formation of a continuous layer of soft tissue along the faces of the implant which are parallel to the loading direction. This was predicted to be correlated with the high levels of distortional strain transferred through the solid component of the stimulus. It was also predicted that the external threads on the implant, redistribute the interfacial load, thus help reduce the high distortional stimulus and also help the cells to differentiate to bone tissue. In addition, the region underneath the implant apex was predicted to experience high fluid stimulus that results in the development of soft tissue. The relationship between the variables considered in this study and the outcome measures, BV and BIC, was found to be highly nonlinear. A three-way analysis of variance (ANOVA) of the results was conducted and it showed that micro-motion presents the largest hindrance to bone formation during healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Desferrioxamine for Stimulation of Fracture Healing and Revascularization in a Bone Defect Model

DTIC Science & Technology

2012-02-01

cartilaginous tissue still present. DBM + L-DFO: Fracture gap less evident with more complete bone bridging with denser trabecular bone and less...fracture callus volume by micro-CT, and qualitative histology for callus tissue quality and vascularity in 5 groups (No implant, CS implant, DFO+CS...Weinhold, P. North Carolina Tissue Engineering and Regenerative Medicine Meeting, November 4, 2011; Winston Salem, NC. (presented) • Desferroxamine with

Successful human long-term application of in situ bone tissue engineering

PubMed Central

Horch, Raymund E; Beier, Justus P; Kneser, Ulrich; Arkudas, Andreas

2014-01-01

Tissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor-site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β-tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto-transplanted bone marrow aspirate from the iliac crest. The following post-operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio-venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain-free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor-site defect utilizing TE and RM techniques in human patients with long-term stability. PMID:24801710

Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis

PubMed Central

Cascão, Rita; Finnilä, Mikko A. J.; Lopes, Inês P.; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João E.

2018-01-01

Introduction Arthritis induces joint erosions and skeletal bone fragility. Objectives The main goal of this work was to analyze the early arthritis induced events at bone architecture and mechanical properties at tissue level. Methods Eighty-eight Wistar rats were randomly housed in experimental groups, as follows: adjuvant induced arthritis (AIA) (N = 47) and a control healthy group (N = 41). Rats were monitored during 22 days for the inflammatory score, ankle perimeter and body weight and sacrificed at different time points (11 and 22 days post disease induction). Bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. Results At bone tissue level, measured by nanoindentation, there was a reduction of hardness in the arthritic group, associated with an increase of the ratio of bone concentric to parallel lamellae and of the area of the osteocyte lacuna. In addition, increased bone turnover and changes in the microstructure and mechanical properties were observed in arthritic animals, since the early phase of arthritis, when compared with healthy controls. Conclusion We have shown in an AIA rat model that arthritis induces very early changes at bone turnover, structural degradation and mechanical weakness. Bone tissue level is also affected since the early phase of arthritis, characterized by decreased tissue hardness associated with changes in bone lamella organization and osteocyte lacuna surface. These observations highlight the pertinence of immediate control of inflammation in the initial stages of arthritis. PMID:29315314

Bone strain magnitude is correlated with bone strain rate in tetrapods: implications for models of mechanotransduction

PubMed Central

Aiello, B. R.; Iriarte-Diaz, J.; Blob, R. W.; Butcher, M. T.; Carrano, M. T.; Espinoza, N. R.; Main, R. P.; Ross, C. F.

2015-01-01

Hypotheses suggest that structural integrity of vertebrate bones is maintained by controlling bone strain magnitude via adaptive modelling in response to mechanical stimuli. Increased tissue-level strain magnitude and rate have both been identified as potent stimuli leading to increased bone formation. Mechanotransduction models hypothesize that osteocytes sense bone deformation by detecting fluid flow-induced drag in the bone's lacunar–canalicular porosity. This model suggests that the osteocyte's intracellular response depends on fluid-flow rate, a product of bone strain rate and gradient, but does not provide a mechanism for detection of strain magnitude. Such a mechanism is necessary for bone modelling to adapt to loads, because strain magnitude is an important determinant of skeletal fracture. Using strain gauge data from the limb bones of amphibians, reptiles, birds and mammals, we identified strong correlations between strain rate and magnitude across clades employing diverse locomotor styles and degrees of rhythmicity. The breadth of our sample suggests that this pattern is likely to be a common feature of tetrapod bone loading. Moreover, finding that bone strain magnitude is encoded in strain rate at the tissue level is consistent with the hypothesis that it might be encoded in fluid-flow rate at the cellular level, facilitating bone adaptation via mechanotransduction. PMID:26063842

Functional grading of mineral and collagen in the attachment of tendon to bone.

PubMed

Genin, Guy M; Kent, Alistair; Birman, Victor; Wopenka, Brigitte; Pasteris, Jill D; Marquez, Pablo J; Thomopoulos, Stavros

2009-08-19

Attachment of dissimilar materials is a major challenge because high levels of localized stress may develop at their interfaces. An effective biologic solution to this problem exists at one of nature's most extreme interfaces: the attachment of tendon (a compliant, structural "soft tissue") to bone (a stiff, structural "hard tissue"). The goal of our study was to develop biomechanical models to describe how the tendon-to-bone insertion derives its mechanical properties. We examined the tendon-to-bone insertion and found two factors that give the tendon-to-bone transition a unique grading in mechanical properties: 1), a gradation in mineral concentration, measured by Raman spectroscopy; and 2), a gradation in collagen fiber orientation, measured by polarized light microscopy. Our measurements motivate a new physiological picture of the tissue that achieves this transition, the tendon-to-bone insertion, as a continuous, functionally graded material. Our biomechanical model suggests that the experimentally observed increase in mineral accumulation within collagen fibers can provide significant stiffening of the partially mineralized fibers, but only for concentrations of mineral above a "percolation threshold" corresponding to formation of a mechanically continuous mineral network within each collagen fiber (e.g., the case of mineral connectivity extending from one end of the fiber to the other). Increasing dispersion in the orientation distribution of collagen fibers from tendon to bone is a second major determinant of tissue stiffness. The combination of these two factors may explain the nonmonotonic variation of stiffness over the length of the tendon-to-bone insertion reported previously. Our models explain how tendon-to-bone attachment is achieved through a functionally graded material composition, and provide targets for tissue engineered surgical interventions and biomimetic material interfaces.

SU-C-213-01: 3D Printed Patient Specific Phantom Composed of Bone and Soft Tissue Substitute Plastics for Radiation Therapy

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

Ehler, E; Sterling, D; Higgins, P

Purpose: 3D printed phantoms constructed of multiple tissue approximating materials could be useful in both clinical and research aspects of radiotherapy. This work describes a 3D printed phantom constructed with tissue substitute plastics for both bone and soft tissue; air cavities were included as well. Methods: 3D models of an anonymized nasopharynx patient were generated for air cavities, soft tissues, and bone, which were segmented by Hounsfield Unit (HU) thresholds. HU thresholds were chosen to define air-to-soft tissue boundaries of 0.65 g/cc and soft tissue-to-bone boundaries of 1.18 g/cc based on clinical HU to density tables. After evaluation of severalmore » composite plastics, a bone tissue substitute was identified as an acceptable material for typical radiotherapy x-ray energies, composed of iron and PLA plastic. PET plastic was determined to be an acceptable soft tissue substitute. 3D printing was performed on a consumer grade dual extrusion fused deposition model 3D printer. Results: MVCT scans of the 3D printed heterogeneous phantom were acquired. Rigid image registration of the patient and the 3D printed phantom scans was performed. The average physical density of the soft tissue and bone regions was 1.02 ± 0.08 g/cc and 1.39 ± 0.14 g/cc, respectively, for the patient kVCT scan. In the 3D printed phantom MVCT scan, the average density of the soft tissue and bone was 1.01 ± 0.09 g/cc and 1.44 ± 0.12 g/cc, respectively. Conclusion: A patient specific phantom, constructed of heterogeneous tissue substitute materials was constructed by 3D printing. MVCT of the 3D printed phantom showed realistic tissue densities were recreated by the 3D printing materials. Funding provided by intra-department grant by University of Minnesota Department of Radiation Oncology.« less

Skeletal dosimetry models for alpha-particles for use in molecular radiotherapy

NASA Astrophysics Data System (ADS)

Watchman, Christopher J.

Molecular radiotherapy is a cancer treatment methodology whereby a radionuclide is combined with a biologically active molecule to preferentially target cancer cells. Alpha-particle emitting radionuclides show significant potential for use in molecular radiotherapy due to the short range of the alpha-particles in tissue and their high rates of energy deposition. Current radiation dosimetry models used to assess alpha emitter dose in the skeleton were developed originally for occupational applications. In medical dosimetry, individual variability in uptake, translocation and other biological factors can result in poor correlation of clinical outcome with marrow dose estimates determined using existing skeletal models. Methods presented in this work were developed in response to the need for dosimetry models which account for these biological and patient-specific factors. Dosimetry models are presented for trabecular bone alpha particle dosimetry as well as a model for cortical bone dosimetry. These radiation transport models are the 3D chord-based infinite spongiosa transport model (3D-CBIST) and the chord-based infinite cortical transport model (CBICT), respectively. Absorbed fraction data for several skeletal tissues for several subjects are presented. Each modeling strategy accounts for biological parameters, such as bone marrow cellularity, not previously incorporated into alpha-particle skeletal dosimetry models used in radiation protection. Using these data a study investigating the variability in alpha-particle absorbed fractions in the human skeleton is also presented. Data is also offered relating skeletal tissue masses in individual bone sites for a range of ages. These data are necessary for dose calculations and have previously only been available as whole body tissue masses. A revised 3D-CBIST model is also presented which allows for changes in endosteum thickness to account for revised target cell location of tissues involved in the radiological induction of bone cancer. In addition, new data are presented on the location of bone-marrow stem cells within the marrow cavities of trabecular bone of the pelvis. All results presented in this work may be applied to occupational exposures, but their greatest utility lies in dose assessments for alpha-emitters in molecular radiotherapy.

Bone fracture healing in mechanobiological modeling: A review of principles and methods.

PubMed

Ghiasi, Mohammad S; Chen, Jason; Vaziri, Ashkan; Rodriguez, Edward K; Nazarian, Ara

2017-06-01

Bone fracture is a very common body injury. The healing process is physiologically complex, involving both biological and mechanical aspects. Following a fracture, cell migration, cell/tissue differentiation, tissue synthesis, and cytokine and growth factor release occur, regulated by the mechanical environment. Over the past decade, bone healing simulation and modeling has been employed to understand its details and mechanisms, to investigate specific clinical questions, and to design healing strategies. The goal of this effort is to review the history and the most recent work in bone healing simulations with an emphasis on both biological and mechanical properties. Therefore, we provide a brief review of the biology of bone fracture repair, followed by an outline of the key growth factors and mechanical factors influencing it. We then compare different methodologies of bone healing simulation, including conceptual modeling (qualitative modeling of bone healing to understand the general mechanisms), biological modeling (considering only the biological factors and processes), and mechanobiological modeling (considering both biological aspects and mechanical environment). Finally we evaluate different components and clinical applications of bone healing simulation such as mechanical stimuli, phases of bone healing, and angiogenesis.

[Differential expression genes of bone tissues surrounding implants in diabetic rats by gene chip].

PubMed

Wang, Xin-xin; Ma, Yue; Li, Qing; Jiang, Bao-qi; Lan, Jing

2012-10-01

To compare mRNA expression profiles of bone tissues surrounding implants between normal rats and rats with diabetes using microarray technology. Six Wistar rats were randomly selected and divided into normal model group and diabetic group. Diabetic model condition was established by injecting Streptozotocin into peritoneal space. Titanium implants were implanted into the epiphyseal end of the rats' tibia. Bone tissues surrounding implant were harvested and sampled after 3 months to perform comprehensive RNA gene expression profiling, including 17983 for genome-wide association study.GO analysis was used to compare different gene expression and real-time PCR was used to confirm the results on core samples. The results indicated that there were 1084 differential gene expression. In the diabetic model, there were 352 enhanced expression genes, 732 suppressed expression genes. GO analysis involved 1154 different functional type. Osteoblast related gene expressions in bone tissue samples of diabetic rats were decreased, and lipid metabolism pathway related gene expression was increased.

Bone Tissue Engineering Under Xenogeneic-Free Conditions in a Large Animal Model as a Basis for Early Clinical Applicability.

PubMed

Weigand, Annika; Beier, Justus P; Schmid, Rafael; Knorr, Tobias; Kilian, David; Götzl, Rebekka; Gerber, Thomas; Horch, Raymund E; Boos, Anja M

2017-03-01

For decades, researchers have been developing a range of promising strategies in bone tissue engineering with the aim of producing a significant clinical benefit over existing therapies. However, a major problem concerns the traditional use of xenogeneic substances for the expansion of cells, which complicates direct clinical transfer. The study's aim was to establish a totally autologous sheep model as a basis for further preclinical studies and future clinical application. Ovine mesenchymal stromal cells (MSC) were cultivated in different concentrations (0%, 2%, 5%, 10%, and 25%) of either autologous serum (AS) or fetal calf serum (FCS). With an increase of serum concentration, enhanced metabolic activity and proliferation could be observed. There were minor differences between MSC cultivated in AS or FCS, comparing gene and protein expression of osteogenic and stem cell markers, morphology, and osteogenic differentiation. MSC implanted subcutaneously in the sheep model, together with a nanostructured bone substitute, either in stable block or moldable putty form, induced similar vascularization and remodeling of the bone substitute irrespective of cultivation of MSC in AS or FCS and osteogenic differentiation. The bone substitute in block form together with MSC proved particularly advantageous in the induction of ectopic bone formation compared to the cell-free control and putty form. It could be demonstrated that AS is suitable for replacement of FCS for cultivation of ovine MSC for bone tissue engineering purposes. Substantial progress has been made in the development of a strictly xenogeneic-free preclinical animal model to bring future clinical application of bone tissue engineering strategies within reach.

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

PubMed Central

Samorezov, Julia E.; Alsberg, Eben

2015-01-01

Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo. PMID:25445719

Multiscale Mathematical Modeling in Dental Tissue Engineering: Toward Computer-Aided Design of a Regenerative System Based on Hydroxyapatite Granules, Focussing on Early and Mid-Term Stiffness Recovery

PubMed Central

Scheiner, Stefan; Komlev, Vladimir S.; Gurin, Alexey N.; Hellmich, Christian

2016-01-01

We here explore for the very first time how an advanced multiscale mathematical modeling approach may support the design of a provenly successful tissue engineering concept for mandibular bone. The latter employs double-porous, potentially cracked, single millimeter-sized granules packed into an overall conglomerate-type scaffold material, which is then gradually penetrated and partially replaced by newly grown bone tissue. During this process, the newly developing scaffold-bone compound needs to attain the stiffness of mandibular bone under normal physiological conditions. In this context, the question arises how the compound stiffness is driven by the key design parameters of the tissue engineering system: macroporosity, crack density, as well as scaffold resorption/bone formation rates. We here tackle this question by combining the latest state-of-the-art mathematical modeling techniques in the field of multiscale micromechanics, into an unprecedented suite of highly efficient, semi-analytically defined computation steps resolving several levels of hierarchical organization, from the millimeter- down to the nanometer-scale. This includes several types of homogenization schemes, namely such for porous polycrystals with elongated solid elements, for cracked matrix-inclusion composites, as well as for assemblies of coated spherical compounds. Together with the experimentally known stiffnesses of hydroxyapatite crystals and mandibular bone tissue, the new mathematical model suggests that early stiffness recovery (i.e., within several weeks) requires total avoidance of microcracks in the hydroxyapatite scaffolds, while mid-term stiffness recovery (i.e., within several months) is additionally promoted by provision of small granule sizes, in combination with high bone formation and low scaffold resorption rates. PMID:27708584

A novel adaptive algorithm for 3D finite element analysis to model extracortical bone growth.

PubMed

Cheong, Vee San; Blunn, Gordon W; Coathup, Melanie J; Fromme, Paul

2018-02-01

Extracortical bone growth with osseointegration of bone onto the shaft of massive bone tumour implants is an important clinical outcome for long-term implant survival. A new computational algorithm combining geometrical shape changes and bone adaptation in 3D Finite Element simulations has been developed, using a soft tissue envelope mesh, a novel concept of osteoconnectivity, and bone remodelling theory. The effects of varying the initial tissue density, spatial influence function and time step were investigated. The methodology demonstrated good correspondence to radiological results for a segmental prosthesis.

In vitro osteogenesis of human stem cells by using a three-dimensional perfusion bioreactor culture system: a review.

PubMed

Ceccarelli, Gabriele; Bloise, Nora; Vercellino, Marco; Battaglia, Rosalia; Morgante, Lucia; De Angelis, Maria Gabriella Cusella; Imbriani, Marcello; Visai, Livia

2013-04-01

Tissue engineering (by culturing cells on appropriate scaffolds, and using bioreactors to drive the correct bone structure formation) is an attractive alternative to bone grafting or implantation of bone substitutes. Osteogenesis is a biological process that involves many molecular intracellular pathways organized to optimize bone modeling. The use of bioreactor systems and especially the perfusion bioreactor, provides both the technological means to reveal fundamental mechanisms of cell function in a 3D environment, and the potential to improve the quality of engineered tissues. In this mini-review all the characteristics for the production of an appropriate bone construct are analyzed: the stem cell source, scaffolds useful for the seeding of pre-osteoblastic cells and the effects of fluid flow on differentiation and proliferation of bone precursor cells. By automating and standardizing tissue manufacture in controlled closed systems, engineered tissues may reduce the gap between the process of bone formation in vitro and subsequent graft of bone substitutes in vivo.

Guided bone generation in a rabbit mandible model after periosteal expansion with an osmotic tissue expander.

PubMed

Abrahamsson, Peter; Isaksson, Sten; Andersson, Gunilla

2011-11-01

To evaluate the space-maintaining capacity of titanium mesh covered by a collagen membrane after soft tissue expansion on the lateral border of the mandible in rabbits, and to assess bone quantity and quality using autogenous particulate bone or bone-substitute (Bio-Oss(®) ), and if soft tissue ingrowth can be avoided by covering the mesh with a collagen membrane. In 11 rabbits, a self-inflatable soft tissue expander was placed under the lateral mandibular periosteum via an extra-oral approach. After 2 weeks, the expanders were removed and a particulated onlay bone graft and deproteinized bovine bone mineral (DBBM) (Bio-Oss(®) ) were placed in the expanded area and covered by a titanium mesh. The bone and DBBM were separated in two compartments under the mesh with a collagen membrane in between. The mesh was then covered with a collagen membrane. After 3 months, the animals were sacrificed and specimens were collected for histology. The osmotic soft tissue expander created a subperiosteal pocket and a ridge of new bone formed at the edges of the expanded periosteum in all sites. After the healing period of 3 months, no soft tissue dehiscence was recorded. The mean bone fill was 58.1±18% in the bone grafted area and 56.9±13.7% in the DBBM area. There was no significant difference between the autologous bone graft and the DDBM under the titanium mesh with regard to the total bone area or the mineralized bone area. Scanning electron microscopy showed that new bone was growing in direct contact with the DBBM particles and the titanium mesh. There is a soft tissue ingrowth even after soft tissue expansion and protection of the titanium mesh with a collagen membrane. This study confirms that an osmotic soft tissue expander creates a surplus of periosteum and soft tissue, and that new bone can subsequently be generated under a titanium mesh with the use of an autologous bone graft or DBBM. © 2011 John Wiley & Sons A/S.

Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies for Large Segmental Bone Defects using the Chronic Caprine Tibial Defect Model

DTIC Science & Technology

2014-10-01

histology, and microCT analysis. In the current phase of work he will receive more specialized ` training and orientation to microCT analysis...fibrous connective tissue. • Performed histology on goat autogenous bone graft which demonstrated that the quantity and quality of cancellous bone graft

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.

Successful human long-term application of in situ bone tissue engineering.

PubMed

Horch, Raymund E; Beier, Justus P; Kneser, Ulrich; Arkudas, Andreas

2014-07-01

Tissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor-site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β-tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto-transplanted bone marrow aspirate from the iliac crest. The following post-operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio-venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain-free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor-site defect utilizing TE and RM techniques in human patients with long-term stability. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Challenges in engineering osteochondral tissue grafts with hierarchical structures.

PubMed

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.

"Black Bone" MRI: a novel imaging technique for 3D printing.

PubMed

Eley, Karen A; Watt-Smith, Stephen R; Golding, Stephen J

2017-03-01

Three-dimensionally printed anatomical models are rapidly becoming an integral part of pre-operative planning of complex surgical cases. We have previously reported the "Black Bone" MRI technique as a non-ionizing alternative to CT. Segmentation of bone becomes possible by minimizing soft tissue contrast to enhance the bone-soft tissue boundary. The objectives of this study were to ascertain the potential of utilizing this technique to produce three-dimensional (3D) printed models. "Black Bone" MRI acquired from adult volunteers and infants with craniosynostosis were 3D rendered and 3D printed. A custom phantom provided a surrogate marker of accuracy permitting comparison between direct measurements and 3D printed models created by segmenting both CT and "Black Bone" MRI data sets using two different software packages. "Black Bone" MRI was successfully utilized to produce 3D models of the craniofacial skeleton in both adults and an infant. Measurements of the cube phantom and 3D printed models demonstrated submillimetre discrepancy. In this novel preliminary study exploring the potential of 3D printing from "Black Bone" MRI data, the feasibility of producing anatomical 3D models has been demonstrated, thus offering a potential non-ionizing alterative to CT for the craniofacial skeleton.

Energy deposition at the bone-tissue interface from nuclear fragments produced by high-energy nucleons

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Hajnal, Ferenc; Wilson, John W.

1990-01-01

The transport of nuclear fragmentation recoils produced by high-energy nucleons in the region of the bone-tissue interface is considered. Results for the different flux and absorbed dose for recoils produced by 1 GeV protons are presented in a bidirectional transport model. The energy deposition in marrow cavities is seen to be enhanced by recoils produced in bone. Approximate analytic formulae for absorbed dose near the interface region are also presented for a simplified range-energy model.

A poroelastic finite element model of the bone-cartilage unit to determine the effects of changes in permeability with osteoarthritis.

PubMed

Stender, Michael E; Regueiro, Richard A; Ferguson, Virginia L

2017-02-01

The changes experienced in synovial joints with osteoarthritis involve coupled chemical, biological, and mechanical processes. The aim of this study was to investigate the consequences of increasing permeability in articular cartilage (AC), calcified cartilage (CC), subchondral cortical bone (SCB), and subchondral trabecular bone (STB) as observed with osteoarthritis. Two poroelastic finite element models were developed using a depth-dependent anisotropic model of AC with strain-dependent permeability and poroelastic models of calcified tissues (CC, SCB, and STB). The first model simulated a bone-cartilage unit (BCU) in uniaxial unconfined compression, while the second model simulated spherical indentation of the AC surface. Results indicate that the permeability of AC is the primary determinant of the BCU's poromechanical response while the permeability of calcified tissues exerts no appreciable effect on the force-indentation response of the BCU. In spherical indentation simulations with osteoarthritic permeability properties, fluid velocities were larger in magnitude and distributed over a smaller area compared to normal tissues. In vivo, this phenomenon would likely lead to chondrocyte death, tissue remodeling, alterations in joint lubrication, and the progression of osteoarthritis. For osteoarthritic and normal tissue permeability values, fluid flow was predicted to occur across the osteochondral interface. These results help elucidate the consequences of increases in the permeability of the BCU that occur with osteoarthritis. Furthermore, this study may guide future treatments to counteract osteoarthritis.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.

PubMed

Cheung, Laurence C; Strickland, Deborah H; Howlett, Meegan; Ford, Jette; Charles, Adrian K; Lyons, Karen M; Brigstock, David R; Goldschmeding, Roel; Cole, Catherine H; Alexander, Warren S; Kees, Ursula R

2014-07-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. Copyright© Ferrata Storti Foundation.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

PubMed Central

Cheung, Laurence C.; Strickland, Deborah H.; Howlett, Meegan; Ford, Jette; Charles, Adrian K.; Lyons, Karen M.; Brigstock, David R.; Goldschmeding, Roel; Cole, Catherine H.; Alexander, Warren S.; Kees, Ursula R.

2014-01-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. PMID:24727816

Computing dispersion curves of elastic/viscoelastic transversely-isotropic bone plates coupled with soft tissue and marrow using semi-analytical finite element (SAFE) method.

PubMed

Nguyen, Vu-Hieu; Tran, Tho N H T; Sacchi, Mauricio D; Naili, Salah; Le, Lawrence H

2017-08-01

We present a semi-analytical finite element (SAFE) scheme for accurately computing the velocity dispersion and attenuation in a trilayered system consisting of a transversely-isotropic (TI) cortical bone plate sandwiched between the soft tissue and marrow layers. The soft tissue and marrow are mimicked by two fluid layers of finite thickness. A Kelvin-Voigt model accounts for the absorption of all three biological domains. The simulated dispersion curves are validated by the results from the commercial software DISPERSE and published literature. Finally, the algorithm is applied to a viscoelastic trilayered TI bone model to interpret the guided modes of an ex-vivo experimental data set from a bone phantom. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tooth Eruption Results from Bone Remodelling Driven by Bite Forces Sensed by Soft Tissue Dental Follicles: A Finite Element Analysis

PubMed Central

Sarrafpour, Babak; Swain, Michael; Li, Qing; Zoellner, Hans

2013-01-01

Intermittent tongue, lip and cheek forces influence precise tooth position, so we here examine the possibility that tissue remodelling driven by functional bite-force-induced jaw-strain accounts for tooth eruption. Notably, although a separate true ‘eruptive force’ is widely assumed, there is little direct evidence for such a force. We constructed a three dimensional finite element model from axial computerized tomography of an 8 year old child mandible containing 12 erupted and 8 unerupted teeth. Tissues modelled included: cortical bone, cancellous bone, soft tissue dental follicle, periodontal ligament, enamel, dentine, pulp and articular cartilage. Strain and hydrostatic stress during incisive and unilateral molar bite force were modelled, with force applied via medial and lateral pterygoid, temporalis, masseter and digastric muscles. Strain was maximal in the soft tissue follicle as opposed to surrounding bone, consistent with follicle as an effective mechanosensor. Initial numerical analysis of dental follicle soft tissue overlying crowns and beneath the roots of unerupted teeth was of volume and hydrostatic stress. To numerically evaluate biological significance of differing hydrostatic stress levels normalized for variable finite element volume, ‘biological response units’ in Nmm were defined and calculated by multiplication of hydrostatic stress and volume for each finite element. Graphical representations revealed similar overall responses for individual teeth regardless if incisive or right molar bite force was studied. There was general compression in the soft tissues over crowns of most unerupted teeth, and general tension in the soft tissues beneath roots. Not conforming to this pattern were the unerupted second molars, which do not erupt at this developmental stage. Data support a new hypothesis for tooth eruption, in which the follicular soft tissues detect bite-force-induced bone-strain, and direct bone remodelling at the inner surface of the surrounding bony crypt, with the effect of enabling tooth eruption into the mouth. PMID:23554928

Tooth eruption results from bone remodelling driven by bite forces sensed by soft tissue dental follicles: a finite element analysis.

PubMed

Sarrafpour, Babak; Swain, Michael; Li, Qing; Zoellner, Hans

2013-01-01

Intermittent tongue, lip and cheek forces influence precise tooth position, so we here examine the possibility that tissue remodelling driven by functional bite-force-induced jaw-strain accounts for tooth eruption. Notably, although a separate true 'eruptive force' is widely assumed, there is little direct evidence for such a force. We constructed a three dimensional finite element model from axial computerized tomography of an 8 year old child mandible containing 12 erupted and 8 unerupted teeth. Tissues modelled included: cortical bone, cancellous bone, soft tissue dental follicle, periodontal ligament, enamel, dentine, pulp and articular cartilage. Strain and hydrostatic stress during incisive and unilateral molar bite force were modelled, with force applied via medial and lateral pterygoid, temporalis, masseter and digastric muscles. Strain was maximal in the soft tissue follicle as opposed to surrounding bone, consistent with follicle as an effective mechanosensor. Initial numerical analysis of dental follicle soft tissue overlying crowns and beneath the roots of unerupted teeth was of volume and hydrostatic stress. To numerically evaluate biological significance of differing hydrostatic stress levels normalized for variable finite element volume, 'biological response units' in Nmm were defined and calculated by multiplication of hydrostatic stress and volume for each finite element. Graphical representations revealed similar overall responses for individual teeth regardless if incisive or right molar bite force was studied. There was general compression in the soft tissues over crowns of most unerupted teeth, and general tension in the soft tissues beneath roots. Not conforming to this pattern were the unerupted second molars, which do not erupt at this developmental stage. Data support a new hypothesis for tooth eruption, in which the follicular soft tissues detect bite-force-induced bone-strain, and direct bone remodelling at the inner surface of the surrounding bony crypt, with the effect of enabling tooth eruption into the mouth.

Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model

PubMed Central

Anzai, Jun; Nagayasu-Tanaka, Toshie; Terashima, Akio; Asano, Taiji; Yamada, Satoru; Nozaki, Takenori; Kitamura, Masahiro; Murakami, Shinya

2016-01-01

The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (μCT). After FGF-2 (0.3%) or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC) were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using μCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological healing process. PMID:27391131

A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells.

PubMed

Hao, Sijie; Ha, Laura; Cheng, Gong; Wan, Yuan; Xia, Yiqiu; Sosnoski, Donna M; Mastro, Andrea M; Zheng, Si-Yang

2018-03-01

Bone metastasis occurs at ≈70% frequency in metastatic breast cancer. The mechanisms used by tumors to hijack the skeleton, promote bone metastases, and confer therapeutic resistance are poorly understood. This has led to the development of various bone models to investigate the interactions between cancer cells and host bone marrow cells and related physiological changes. However, it is challenging to perform bone studies due to the difficulty in periodic sampling. Herein, a bone-on-a-chip (BC) is reported for spontaneous growth of a 3D, mineralized, collagenous bone tissue. Mature osteoblastic tissue of up to 85 µm thickness containing heavily mineralized collagen fibers naturally formed in 720 h without the aid of differentiation agents. Moreover, co-culture of metastatic breast cancer cells is examined with osteoblastic tissues. The new bone-on-a-chip design not only increases experimental throughput by miniaturization, but also maximizes the chances of cancer cell interaction with bone matrix of a concentrated surface area and facilitates easy, frequent observation. As a result, unique hallmarks of breast cancer bone colonization, previously confirmed only in vivo, are observed. The spontaneous 3D BC keeps the promise as a physiologically relevant model for the in vitro study of breast cancer bone metastasis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of micromorphology of cortical bone tissue on crack propagation under dynamic loading

NASA Astrophysics Data System (ADS)

Wang, Mayao; Gao, Xing; Abdel-Wahab, Adel; Li, Simin; Zimmermann, Elizabeth A.; Riedel, Christoph; Busse, Björn; Silberschmidt, Vadim V.

2015-09-01

Structural integrity of bone tissue plays an important role in daily activities of humans. However, traumatic incidents such as sports injuries, collisions and falls can cause bone fracture, servere pain and mobility loss. In addition, ageing and degenerative bone diseases such as osteoporosis can increase the risk of fracture [1]. As a composite-like material, a cortical bone tissue is capable of tolerating moderate fracture/cracks without complete failure. The key to this is its heterogeneously distributed microstructural constituents providing both intrinsic and extrinsic toughening mechanisms. At micro-scale level, cortical bone can be considered as a four-phase composite material consisting of osteons, Haversian canals, cement lines and interstitial matrix. These microstructural constituents can directly affect local distributions of stresses and strains, and, hence, crack initiation and propagation. Therefore, understanding the effect of micromorphology of cortical bone on crack initiation and propagation, especially under dynamic loading regimes is of great importance for fracture risk evaluation. In this study, random microstructures of a cortical bone tissue were modelled with finite elements for four groups: healthy (control), young age, osteoporosis and bisphosphonate-treated, based on osteonal morphometric parameters measured from microscopic images for these groups. The developed models were loaded under the same dynamic loading conditions, representing a direct impact incident, resulting in progressive crack propagation. An extended finite-element method (X-FEM) was implemented to realize solution-dependent crack propagation within the microstructured cortical bone tissues. The obtained simulation results demonstrate significant differences due to micromorphology of cortical bone, in terms of crack propagation characteristics for different groups, with the young group showing highest fracture resistance and the senior group the lowest.

Does PEEK/HA Enhance Bone Formation Compared With PEEK in a Sheep Cervical Fusion Model?

PubMed

Walsh, William R; Pelletier, Matthew H; Bertollo, Nicky; Christou, Chris; Tan, Chris

2016-11-01

Polyetheretherketone (PEEK) has a wide range of clinical applications but does not directly bond to bone. Bulk incorporation of osteoconductive materials including hydroxyapatite (HA) into the PEEK matrix is a potential solution to address the formation of a fibrous tissue layer between PEEK and bone and has not been tested. Using in vivo ovine animal models, we asked: (1) Does PEEK-HA improve cortical and cancellous bone ongrowth compared with PEEK? (2) Does PEEK-HA improve bone ongrowth and fusion outcome in a more challenging functional ovine cervical fusion model? The in vivo responses of PEEK-HA Enhanced and PEEK-OPTIMA ® Natural were evaluated for bone ongrowth in the form of dowels implanted in the cancellous and cortical bone of adult sheep and examined at 4 and 12 weeks as well as interbody cervical fusion at 6, 12, and 26 weeks. The bone-implant interface was evaluated with radiographic and histologic endpoints for a qualitative assessment of direct bone contact of an intervening fibrous tissue later. Gamma-irradiated cortical allograft cages were evaluated as well. Incorporating HA into the PEEK matrix resulted in more direct bone apposition as opposed to the fibrous tissue interface with PEEK alone in the bone ongrowth as well as interbody cervical fusions. No adverse reactions were found at the implant-bone interface for either material. Radiography and histology revealed resorption and fracture of the allograft devices in vivo. Incorporating HA into PEEK provides a more favorable environment than PEEK alone for bone ongrowth. Cervical fusion was improved with PEEK-HA compared with PEEK alone as well as allograft bone interbody devices. Improving the bone-implant interface with a PEEK device by incorporating HA may improve interbody fusion results and requires further clinical studies.

Interstitial ultrasound ablation of tumors within or adjacent to bone: Contributions of preferential heating at the bone surface

NASA Astrophysics Data System (ADS)

Scott, Serena J.; Prakash, Punit; Salgaonkar, Vasant; Jones, Peter D.; Cam, Richard N.; Han, Misung; Rieke, Viola; Burdette, E. Clif; Diederich, Chris J.

2013-02-01

Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters. Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose < 6 CEM43°C and T < 45°C) sensitive structures behind ablated bone. In 3D patient-specific simulations, tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose > 240 CEM43°C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other heating modalities.

Macrodamage Accumulation Model for a Human Femur

PubMed Central

2017-01-01

The objective of this study was to more fully understand the mechanical behavior of bone tissue that is important to find an alternative material to be used as an implant and to develop an accurate model to predict the fracture of the bone. Predicting and preventing bone failure is an important area in orthopaedics. In this paper, the macrodamage accumulation models in the bone tissue have been investigated. Phenomenological models for bone damage have been discussed in detail. In addition, 3D finite element model of the femur prepared from imaging data with both cortical and trabecular structures is delineated using MIMICS and ANSYS® and simulated as a composite structure. The damage accumulation occurring during cyclic loading was analyzed for fatigue scenario. We found that the damage accumulates sooner in the multiaxial than in the uniaxial loading condition for the same number of cycles, and the failure starts in the cortical bone. The damage accumulation behavior seems to follow a three-stage growth: a primary phase, a secondary phase of damage growth marked by linear damage growth, and a tertiary phase that leads to failure. Finally, the stiffness of the composite bone comprising the cortical and trabecular bone was significantly different as expected. PMID:28951659

Bone scaffolds with homogeneous and discrete gradient mechanical properties.

PubMed

Jelen, C; Mattei, G; Montemurro, F; De Maria, C; Mattioli-Belmonte, M; Vozzi, G

2013-01-01

Bone TE uses a scaffold either to induce bone formation from surrounding tissue or to act as a carrier or template for implanted bone cells or other agents. We prepared different bone tissue constructs based on collagen, gelatin and hydroxyapatite using genipin as cross-linking agent. The fabricated construct did not present a release neither of collagen neither of genipin over its toxic level in the surrounding aqueous environment. Each scaffold has been mechanically characterized with compression, swelling and creep tests, and their respective viscoelastic mechanical models were derived. Mechanical characterization showed a practically elastic behavior of all samples and that compressive elastic modulus basically increases as content of HA increases, and it is strongly dependent on porosity and water content. Moreover, by considering that gradients in cellular and extracellular architecture as well as in mechanical properties are readily apparent in native tissues, we developed discrete functionally graded scaffolds (discrete FGSs) in order to mimic the graded structure of bone tissue. These new structures were mechanically characterized showing a marked anisotropy as the native bone tissue. Results obtained have shown FGSs could represent valid bone substitutes. Copyright © 2012 Elsevier B.V. All rights reserved.

Mathematical Model of Bone Regeneration in a Porous Implant

NASA Astrophysics Data System (ADS)

Maslov, L. B.

2017-07-01

A mathematical model of the reparative regeneration of bone tissue governed by the law of cell differentiation and action of an external periodic mechanical loading is presented. The model allows one to study the recovery processes of injured human locomotor system elements under a dynamic loading and to theoretically substantiate the choice of an optimum periodic impact on the defective tissues for their fastest and steady healing.

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

DTIC Science & Technology

2012-05-10

1% peni - cillin/streptomycin, and 50 ng/mL recombinant rat VEGF-C (Promocell, Heidelberg, Germany). The media were changed every other day for 8...various animal models that have demonstrated an enhanced osteogenic effect after treating bone allografts with adipose tissue or bone marrow-derived... enhanced 1560 CORNEJO ET AL. performance of bone allografts using osteogenic differentiated adipose derived mesenchymal stem cells. Biomaterials 32, 8880

Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

PubMed Central

Mendonça, Maira L.; Batista, Sérgio L.; Nogueira-Barbosa, Marcello H.; Salmon, Carlos E.G.; de Paula, Francisco J.A.

2016-01-01

OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01). Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%). The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005), but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity. PMID:27626477

In vivo characterization of Hyalonect, a novel biodegradable surgical mesh.

PubMed

Rhodes, Nicholas P; Hunt, John A; Longinotti, Cristina; Pavesio, Alessandra

2011-06-01

Musculoskeletal reconstructive surgery often requires removal of significant quantities of bone tissue, such as the periosteum, causing critical problems following surgery like friction between different tissues and adhesion of soft tissues to the underlying bone. We studied the long-term host response and closure of large bone defects for periosteal reconstruction using Hyalonect, a novel membrane comprising knitted fibers of esterified hyaluronan, (HYAFF11). For biological characterization, 162 rats were used in a defect model in which a section of the dorsal muscular fascia was removed, and the membrane behavior observed over 540 d using conventional histology, with sham operated rats as controls. In addition, Hyalonect was used to cover defects made in the humeri of 7 dogs, filled with a variety of conventional bone filling compounds, and the regeneration process observed after 6 wks using histology. Low levels of inflammation were observed in the dorsal muscle fascia defect model, with cellular colonization of the mesh by 30 d, vascularization by 120 days, matrix fiber organization by 270 d, and the appearance of connective tissue identical to the surrounding tissue between 365 and 540 d, without the formation of fibrotic tissue. In addition, Hyalonect was shown to allow the regeneration of bone within the humeral defects whilst preventing fibrotic tissue in-growth, and allowing regeneration of tissue which, by 6 wk, had begun to resemble natural periosteal tissue. Hyalonect is suitable for improving the outcome of the final phases of orthopedic and trauma reconstructive surgical procedures, especially in the reconstruction of periosteal tissue. Copyright © 2011. Published by Elsevier Inc.

Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

PubMed Central

Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

2016-01-01

Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

Novel 3D Tissue Engineered Bone Model, Biomimetic Nanomaterials, and Cold Atmospheric Plasma Technique for Biomedical Applications

NASA Astrophysics Data System (ADS)

Wang, Mian

This thesis research is consist of four chapters, including biomimetic three-dimensional tissue engineered nanostructured bone model for breast cancer bone metastasis study (Chapter one), cold atmospheric plasma for selectively ablating metastatic breast cancer (Chapter two), design of biomimetic and bioactive cold plasma modified nanostructured scaffolds for enhanced osteogenic differentiation of bone marrow derived mesenchymal stem cells (Chapter three), and enhanced osteoblast and mesenchymal stem cell functions on titanium with hydrothermally treated nanocrystalline hydroxyapatite/magnetically treated carbon nanotubes for orthopedic applications (Chapter four). All the thesis research is focused on nanomaterials and the use of cold plasma technique for various biomedical applications.

Development of a 3D bone marrow adipose tissue model.

PubMed

Fairfield, Heather; Falank, Carolyne; Farrell, Mariah; Vary, Calvin; Boucher, Joshua M; Driscoll, Heather; Liaw, Lucy; Rosen, Clifford J; Reagan, Michaela R

2018-01-26

Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. In adipose biology and cancer research, these models serve as physiologically relevant 3D platforms to bridge the divide between 2D cultures and in vivo models, bringing about more reliable and translationally useful data to accelerate benchtop to bedside research. Currently, no model has been developed for bone marrow adipose tissue (BMAT), a novel adipose depot that has previously been overlooked as "filler tissue" but has more recently been recognized as endocrine-signaling and systemically relevant. Herein we describe the development of the first 3D, BMAT model derived from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We found that BMAT models can be stably cultured for at least 3 months in vitro, and that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at least 2 weeks. Upon tumor cell co-culture, delipidation occurred in BMAT adipocytes, suggesting a bidirectional relationship between these two important cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT represents a "healthier," more realistic tissue model that may be useful for elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to identify novel therapeutic targets. In addition, proteomic characterization as well as microarray data (expression of >22,000 genes) coupled with KEGG pathway analysis and gene set expression analysis (GSEA) supported our development of less-inflammatory 3D BMAT compared to 2D culture. In sum, we developed the first 3D, tissue-engineered bone marrow adipose tissue model, which is a versatile, novel model that can be used to study numerous diseases and biological processes involved with the bone marrow. Copyright © 2018. Published by Elsevier Inc.

In vivo tibial stiffness is maintained by whole bone morphology and cross-sectional geometry in growing female mice

PubMed Central

Main, Russell P.; Lynch, Maureen E.; van der Meulen, Marjolein C.H.

2010-01-01

Whole bone morphology, cortical geometry, and tissue material properties modulate skeletal stresses and strains that in turn influence skeletal physiology and remodeling. Understanding how bone stiffness, the relationship between applied load and tissue strain, is regulated by developmental changes in bone structure and tissue material properties is important in implementing biophysical strategies for promoting healthy bone growth and preventing bone loss. The goal of this study was to relate developmental patterns of in vivo whole bone stiffness to whole bone morphology, cross-sectional geometry, and tissue properties using a mouse axial loading model. We measured in vivo tibial stiffness in three age groups (6wks, 10wks, 16wks old) of female C57Bl/6 mice during cyclic tibial compression. Tibial stiffness was then related to cortical geometry, longitudinal bone curvature, and tissue mineral density using microcomputed tomography (microCT). Tibial stiffness and the stresses induced by axial compression were generally maintained from 6 to 16wks of age. Growth-related increases in cortical cross-sectional geometry and longitudinal bone curvature had counteracting effects on induced bone stresses and, therefore, maintained tibial stiffness similarly with growth. Tissue mineral density increased slightly from 6 to 16wks of age, and although the effects of this increase on tibial stiffness were not directly measured, its role in the modulation of whole bone stiffness was likely minor over the age range examined. Thus, whole bone morphology, as characterized by longitudinal curvature, along with cortical geometry, plays an important role in modulating bone stiffness during development and should be considered when evaluating and designing in vivo loading studies and biophysical skeletal therapies. PMID:20673665

[Experimental study of repairing bone defect with tissue engineered bone seeded with autologous red bone marrow and wrapped by pedicled fascial flap].

PubMed

Yang, Xinming; Shi, Wei; Du, Yakun; Meng, Xianyong; Yin, Yanlin

2009-10-01

To investigate the effect of repairing bone defect with tissue engineered bone seeded with the autologous red bone marrow (ARBM) and wrapped by the pedicled fascial flap and provide experimental foundation for clinical application. Thirty-two New Zealand white rabbits (male and/or female) aged 4-5 months old and weighing 2.0-2.5 kg were used to make the experimental model of bilateral 2 cm defect of the long bone and the periosteum in the radius. The tissue engineered bone was prepared by seeding the ARBM obtained from the rabbits on the osteoinductive absorbing material containing BMP. The left side of the experimental model underwent the implantation of autologous tissue engineered bone serving as the control group (group A). While the right side was designed as the experimental group (group B), one 5 cm x 3 cm fascial flap pedicled on the nameless blood vessel along with its capillary network adjacent to the bone defect was prepared using microsurgical technology, and the autologous tissue engineered bone wrapped by the fascial flap was used to fill the bone defect. At 4, 8, 12, and 16 weeks after operation, X-ray exam, absorbance (A) value test, gross morphology and histology observation, morphology quantitative analysis of bone in the reparative area, vascular image analysis on the boundary area were conducted. X-ray films, gross morphology observation, and histology observation: group B was superior to group A in terms of the growth of blood vessel into the implant, the quantity and the speed of the bone trabecula and the cartilage tissue formation, the development of mature bone structure, the remodeling of shaft structure, the reopen of marrow cavity, and the absorbance and degradation of the implant. A value: there was significant difference between two groups 8, 12, and 16 weeks after operation (P < 0.05), and there were significant differences among those three time points in groups A and B (P < 0.05). For the ratio of neonatal trabecula area to the total reparative area, there were significant differences between two groups 4, 8, 12, and 16 weeks after operation (P < 0.05), and there were significant differences among those four time points in group B (P < 0.05). For the vascular regenerative area in per unit area of the junctional zone, group B was superior to group A 4, 8, 12, and 16 weeks after operation (P < 0.05). Tissue engineered bone, seeded with the ARBM and wrapped by the pedicled fascial flap, has a sound reparative effect on bone defect due to its dual role of constructing vascularization and inducing membrane guided tissue regeneration.

Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application

PubMed Central

Wu, Chengtie; Chang, Jiang

2012-01-01

The impact of bone diseases and trauma in the whole world has increased significantly in the past decades. Bioactive glasses are regarded as an important bone regeneration material owing to their generally excellent osteoconductivity and osteostimulativity. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area. The study of MBG for drug/growth factor delivery and bone tissue engineering has grown significantly in the past several years. In this article, we review the recent advances of MBG materials, including the preparation of different forms of MBG, composition–structure relationship, efficient drug/growth factor delivery and bone tissue engineering application. By summarizing our recent research, the interaction of MBG scaffolds with bone-forming cells, the effect of drug/growth factor delivery on proliferation and differentiation of tissue cells and the in vivo osteogenesis of MBG scaffolds are highlighted. The advantages and limitations of MBG for drug delivery and bone tissue engineering have been compared with microsize bioactive glasses and nanosize bioactive glasses. The future perspective of MBG is discussed for bone regeneration application by combining drug delivery with bone tissue engineering and investigating the in vivo osteogenesis mechanism in large animal models. PMID:23741607

Challenges in engineering osteochondral tissue grafts with hierarchical structures Ivana Gadjanski, Gordana Vunjak Novakovic

PubMed Central

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

Introduction A major hurdle in treating osteochondral (OC) defects are the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct-engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. Areas covered This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. Expert opinion A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens, and harnessing of inflammatory responses of the host will likely drive the further progress. PMID:26195329

Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

PubMed Central

Boos, Anja M; Weigand, Annika; Deschler, Gloria; Gerber, Thomas; Arkudas, Andreas; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

2014-01-01

New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation. PMID:25429218

Cortical Bone Mechanical Properties Are Altered in an Animal Model of Progressive Chronic Kidney Disease

PubMed Central

Newman, Christopher L.; Moe, Sharon M.; Chen, Neal X.; Hammond, Max A.; Wallace, Joseph M.; Nyman, Jeffry S.; Allen, Matthew R.

2014-01-01

Chronic kidney disease (CKD), which leads tocortical bone loss and increasedporosity,increases therisk of fracture. Animal models have confirmed that these changes compromise whole bone mechanical properties. Estimates from whole bone testing suggest that material properties are negatively affected, though tissue-level assessmentshavenot been conducted. Therefore, the goal of the present study was to examine changes in cortical bone at different length scales using a rat model with theprogressive development of CKD. At 30 weeks of age (∼75% reduction in kidney function), skeletally mature male Cy/+ rats were compared to their normal littermates. Cortical bone material propertieswere assessed with reference point indentation (RPI), atomic force microscopy (AFM), Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from animals with CKD had higher (+18%) indentation distance increase and first cycle energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader distribution of elastic modulus values in CKD animals witha greater proportion of both higher and lower modulus values compared to normal controls. Yet, tissue composition, collagen morphology, and collagen cross-linking fail to account for these differences. Though the specific skeletal tissue alterations responsible for these mechanical differences remain unclear, these results indicate that cortical bone material properties are altered in these animals and may contribute to the increased fracture risk associated with CKD. PMID:24911162

Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

PubMed Central

Wallace, Joseph M.; Golcuk, Kurtulus; Morris, Michael D.; Kohn, David H.

2010-01-01

Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone. PMID:20033775

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.

Combining coherent hard X-ray tomographies with phase retrieval to generate three-dimensional models of forming bone

NASA Astrophysics Data System (ADS)

Bortel, Emely L.; Langer, Max; Rack, Alexander; Forien, Jean-Baptiste; Duda, Georg N.; Fratzl, Peter; Zaslansky, Paul

2017-11-01

Holotomography, a phase sensitive synchrotron-based μCT modality, is a quantitative 3D imaging method. By exploiting partial spatial X-ray coherence, bones can be imaged volumetrically with high resolution coupled with impressive density sensitivity. This tomographic method reveals the main characteristics of the important tissue compartments in forming bones, including the rapidly-changing soft tissue and the partially or fully mineralized bone regions, while revealing subtle density differences in 3D. Here we show typical results observed within the growing femur bone midshafts of healthy mice that are 1, 3, 7, 10 and 14 days old (postpartum). Our results make use of partially-coherent synchrotron radiation employing inline Fresnel-propagation in multiple tomographic datasets obtained in the imaging beamline ID19 of the ESRF. The exquisite detail creates maps of the juxtaposed soft, partially mineralized and highly mineralized bone revealing the environment in which bone cells create and shape the matrix. This high resolution 3D data is a step towards creating realistic computational models that may be used to study the dynamic processes involved in bone tissue formation and adaptation. Such data will enhance our understanding of the important biomechanical interactions directing maturation and shaping of the bone micro- and macro-geometries.

A Comparative Analysis on Two Types of Oral Implants, Bone-Level and Tissue-Level, with Different Cantilever Lengths of Fixed Prosthesis.

PubMed

Mosavar, Alireza; Nili, Monireh; Hashemi, Sayed Raouf; Kadkhodaei, Mahmoud

2017-06-01

Depending on esthetic, anatomical, and functional aspects, in implant-prosthetic restoration of a completely edentulous jaw, the selection of implant type is highly important; however, bone- and tissue-level implants and their stress distribution in bone have not yet been comparatively investigated. Hence, finite element analysis was used to study the influence of cantilever length in a fixed prosthesis on stress distribution in peri-implant bone around these two types of oral implants. A 3D edentulous mandible was modeled. In simulations, a framework with four posterior cantilever lengths and two types of implants, bone-level and tissue-level, was considered. A compressive load was applied to the distal regions of the cantilevers, and the von-Mises stress of peri-implant bone was investigated. The independent t-test and the Pearson correlation coefficient analyzed the results (α = 0.05). Stresses in the cortical bone around the bone-level implants were greater than those in the tissue-level implants with the same cantilever length. In addition, by extending the cantilever length, the stress values in peri-implant bone increased. Therefore, when the cantilever was at its maximum length, the maximum stress was in cortical bone and around the bone-level distal implants. The results of the present study indicate that treatment with tissue-level implants is potentially more advantageous than with bone-level implants for implant-supported fixed prostheses. © 2015 by the American College of Prosthodontists.

The Metabolic Microenvironment Steers Bone Tissue Regeneration.

PubMed

Loeffler, Julia; Duda, Georg N; Sass, F Andrea; Dienelt, Anke

2018-02-01

Over the past years, basic findings in cancer research have revealed metabolic symbiosis between different cell types to cope with high energy demands under limited nutrient availability. Although this also applies to regenerating tissues with disrupted physiological nutrient and oxygen supply, the impact of this metabolic cooperation and metabolic reprogramming on cellular development, fate, and function during tissue regeneration has widely been neglected so far. With this review, we aim to provide a schematic overview on metabolic links that have a high potential to drive tissue regeneration. As bone is, aside from liver, the only tissue that can regenerate without excessive scar tissue formation, we will use bone healing as an exemplarily model system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling Vascularized Bone Regeneration Within a Porous Biodegradable CaP Scaffold Loaded with Growth Factors

PubMed Central

Sun, X; Kang, Y; Bao, J; Zhang, Y; Yang, Y; Zhou, X

2013-01-01

Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors. PMID:23566802

Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

NASA Technical Reports Server (NTRS)

Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

2012-01-01

Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

Numerical FEM modeling in dental implantology

NASA Astrophysics Data System (ADS)

Roateşi, Iulia; Roateşi, Simona

2016-06-01

This paper is devoted to a numerical approach of the stress and displacement calculation of a system made up of dental implant, ceramic crown and surrounding bone. This is the simulation of a clinical situation involving both biological - the bone tissue, and non-biological - the implant and the crown, materials. On the other hand this problem deals with quite fine technical structure details - the threads, tapers, etc with a great impact in masticatory force transmission. Modeling the contact between the implant and the bone tissue is important to a proper bone-implant interface model and implant design. The authors proposed a three-dimensional numerical model to assess the biomechanical behaviour of this complex structure in order to evaluate its stability by determining the risk zones. A comparison between this numerical analysis and clinical cases is performed and a good agreement is obtained.

The Macular Carotenoids Lutein and Zeaxanthin Are Related to Increased Bone Density in Young Healthy Adults

PubMed Central

Bovier, Emily R.; Hammond, Billy R.

2017-01-01

Lutein (L) and zeaxanthin (Z) status can be quantified by measuring their concentrations both in serum and, non-invasively, in retinal tissue. This has resulted in a unique ability to assess their role in a number of tissues ranging from cardiovascular to central nervous system tissue. Recent reports using animal models have suggested yet another role, a developmental increase in bone mass. To test this, we assessed L and Z status in 63 young healthy adults. LZ status was determined by measuring LZ in serum (using HPLC) and retina tissue (measuring macular pigment optical density, MPOD, using customized heterochromatic flicker photometry). Bone density was measured using dual-energy X-ray absorptiometry (DXA). Although serum LZ was generally not related to bone mass, MPOD was significantly related to bone density in the proximal femur and lumbar spine. In general, our results are consistent with carotenoids, specifically LZ, playing a role in optimal bone health. PMID:28880221

Nanoparticles for bone tissue engineering.

PubMed

Vieira, Sílvia; Vial, Stephanie; Reis, Rui L; Oliveira, J Miguel

2017-05-01

Tissue engineering (TE) envisions the creation of functional substitutes for damaged tissues through integrated solutions, where medical, biological, and engineering principles are combined. Bone regeneration is one of the areas in which designing a model that mimics all tissue properties is still a challenge. The hierarchical structure and high vascularization of bone hampers a TE approach, especially in large bone defects. Nanotechnology can open up a new era for TE, allowing the creation of nanostructures that are comparable in size to those appearing in natural bone. Therefore, nanoengineered systems are now able to more closely mimic the structures observed in naturally occurring systems, and it is also possible to combine several approaches - such as drug delivery and cell labeling - within a single system. This review aims to cover the most recent developments on the use of different nanoparticles for bone TE, with emphasis on their application for scaffolds improvement; drug and gene delivery carriers, and labeling techniques. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:590-611, 2017. © 2017 American Institute of Chemical Engineers.

[Morphological analysis of bone dynamics and metabolic bone disease. Effect of loading on bone tissue].

PubMed

Sakai, Akinori

2011-04-01

We developed a voluntarily climbing animal model to investigate the effect of skeletal loading on bone tissue. At the cross section of the mid-femur, climbing exercise increases outer diameter and area of cortical bone. The mechanical strength of the femur is increased. This change of cortical volume and structure is more marked in anti-gravity exercise, such as climbing and jumping, than aerobic exercise. At the bone marrow area, climbing exercise increases trabecular bone volume and osteoblast number, while it decreases fat volume and adipocyte number. Skeletal loading promotes differentiation from mesenchymal stem cells to osteoblasts and suppresses that to adipocytes by facilitating the signal through PTH÷PTHrP receptor.

Engineering bone tissue substitutes from human induced pluripotent stem cells.

PubMed

de Peppo, Giuseppe Maria; Marcos-Campos, Iván; Kahler, David John; Alsalman, Dana; Shang, Linshan; Vunjak-Novakovic, Gordana; Marolt, Darja

2013-05-21

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.

Bone mechanobiology, gravity and tissue engineering: effects and insights.

PubMed

Ruggiu, Alessandra; Cancedda, Ranieri

2015-12-01

Bone homeostasis strongly depends on fine tuned mechanosensitive regulation signals from environmental forces into biochemical responses. Similar to the ageing process, during spaceflights an altered mechanotransduction occurs as a result of the effects of bone unloading, eventually leading to loss of functional tissue. Although spaceflights represent the best environment to investigate near-zero gravity effects, there are major limitations for setting up experimental analysis. A more feasible approach to analyse the effects of reduced mechanostimulation on the bone is represented by the 'simulated microgravity' experiments based on: (1) in vitro studies, involving cell cultures studies and the use of bioreactors with tissue engineering approaches; (2) in vivo studies, based on animal models; and (3) direct analysis on human beings, as in the case of the bed rest tests. At present, advanced tissue engineering methods allow investigators to recreate bone microenvironment in vitro for mechanobiology studies. This group and others have generated tissue 'organoids' to mimic in vitro the in vivo bone environment and to study the alteration cells can go through when subjected to unloading. Understanding the molecular mechanisms underlying the bone tissue response to mechanostimuli will help developing new strategies to prevent loss of tissue caused by altered mechanotransduction, as well as identifying new approaches for the treatment of diseases via drug testing. This review focuses on the effects of reduced gravity on bone mechanobiology by providing the up-to-date and state of the art on the available data by drawing a parallel with the suitable tissue engineering systems. Copyright © 2014 John Wiley & Sons, Ltd.

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats.

PubMed

Sanbe, Toshihiro; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Tamaki, Naofumi; Yamamoto, Tatsuo

2007-11-01

A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.

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.

Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

PubMed

Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

2015-05-01

During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue ingrowth and remodeling processes of the bone substitute. Extrinsic vessels contribute to faster vascularization and finally anastomose with intrinsic vasculature, allowing microvascular transplantation of the bone substitute after a shorter prevascularization time than using the intrinsic method only. It can be reasonably assumed that the usage of perforated chambers can significantly reduce the time until transplantation of bone constructs. Finally, this study paves the way for further preclinical testing for proof of the concept as a basis for early clinical applicability.

Numerical analysis of standard and modified osteosynthesis in long bone fractures treatment.

PubMed

Sisljagić, Vladimir; Jovanović, Savo; Mrcela, Tomislav; Radić, Radivoje; Selthofer, Robert; Mrcela, Milanka

2010-03-01

The fundamental problem in osteoporotic fracture treatment is significant decrease in bone mass and bone tissue density resulting in decreased firmness and elasticity of osteoporotic bone. Application of standard implants and standard surgical techniques in osteoporotic bone fracture treatment makes it almost impossible to achieve stable osteosynthesis sufficient for early mobility, verticalization and load. Taking into account the form and the size of the contact surface as well as distribution of forces between the osteosynthetic materials and the bone tissue numerical analysis showed advantages of modified osteosynthesis with bone cement filling in the screw bed. The applied numerical model consisted of three sub-models: 3D model from solid elements, 3D cross section of the contact between the plate and the bone and the part of 3D cross section of the screw head and body. We have reached the conclusion that modified osteosynthesis with bone cement resulted in weaker strain in the part of the plate above the fracture fissure, more even strain on the screws, plate and bone, more even strain distribution along all the screws' bodies, significantly greater strain in the part of the screw head opposite to the fracture fissure, firm connection of the screw head and neck and the plate hole with the whole plate and more even bone strain around the screw.

Biological properties of solid free form designed ceramic scaffolds with BMP-2: in vitro and in vivo evaluation.

PubMed

Abarrategi, Ander; Moreno-Vicente, Carolina; Martínez-Vázquez, Francisco Javier; Civantos, Ana; Ramos, Viviana; Sanz-Casado, José Vicente; Martínez-Corriá, Ramón; Perera, Fidel Hugo; Mulero, Francisca; Miranda, Pedro; López-Lacomba, José Luís

2012-01-01

Porous ceramic scaffolds are widely studied in the tissue engineering field due to their potential in medical applications as bone substitutes or as bone-filling materials. Solid free form (SFF) fabrication methods allow fabrication of ceramic scaffolds with fully controlled pore architecture, which opens new perspectives in bone tissue regeneration materials. However, little experimentation has been performed about real biological properties and possible applications of SFF designed 3D ceramic scaffolds. Thus, here the biological properties of a specific SFF scaffold are evaluated first, both in vitro and in vivo, and later scaffolds are also implanted in pig maxillary defect, which is a model for a possible application in maxillofacial surgery. In vitro results show good biocompatibility of the scaffolds, promoting cell ingrowth. In vivo results indicate that material on its own conducts surrounding tissue and allow cell ingrowth, thanks to the designed pore size. Additional osteoinductive properties were obtained with BMP-2, which was loaded on scaffolds, and optimal bone formation was observed in pig implantation model. Collectively, data show that SFF scaffolds have real application possibilities for bone tissue engineering purposes, with the main advantage of being fully customizable 3D structures.

Biological Properties of Solid Free Form Designed Ceramic Scaffolds with BMP-2: In Vitro and In Vivo Evaluation

PubMed Central

Abarrategi, Ander; Moreno-Vicente, Carolina; Martínez-Vázquez, Francisco Javier; Civantos, Ana; Ramos, Viviana; Sanz-Casado, José Vicente; Martínez-Corriá, Ramón; Perera, Fidel Hugo; Mulero, Francisca; Miranda, Pedro; López-Lacomba, José Luís

2012-01-01

Porous ceramic scaffolds are widely studied in the tissue engineering field due to their potential in medical applications as bone substitutes or as bone-filling materials. Solid free form (SFF) fabrication methods allow fabrication of ceramic scaffolds with fully controlled pore architecture, which opens new perspectives in bone tissue regeneration materials. However, little experimentation has been performed about real biological properties and possible applications of SFF designed 3D ceramic scaffolds. Thus, here the biological properties of a specific SFF scaffold are evaluated first, both in vitro and in vivo, and later scaffolds are also implanted in pig maxillary defect, which is a model for a possible application in maxillofacial surgery. In vitro results show good biocompatibility of the scaffolds, promoting cell ingrowth. In vivo results indicate that material on its own conducts surrounding tissue and allow cell ingrowth, thanks to the designed pore size. Additional osteoinductive properties were obtained with BMP-2, which was loaded on scaffolds, and optimal bone formation was observed in pig implantation model. Collectively, data show that SFF scaffolds have real application possibilities for bone tissue engineering purposes, with the main advantage of being fully customizable 3D structures. PMID:22470527

The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders

PubMed Central

2013-01-01

Background We examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF). Methods Rats underwent initial training for 4–6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality. Results Several force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw mechanical allodynia by task week 12. Conclusions Although not consistent in all tissues, we found several significant interactions between the critical musculoskeletal risk factors of force and repetition, consistent with a fatigue failure process in musculoskeletal tissues. Prolonged performance of HRHF tasks exhibited significantly increased risk for musculoskeletal disorders, while performance of moderate level tasks exhibited adaptation to task demands. PMID:24156755

The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders.

PubMed

Barbe, Mary F; Gallagher, Sean; Massicotte, Vicky S; Tytell, Michael; Popoff, Steven N; Barr-Gillespie, Ann E

2013-10-25

We examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF). Rats underwent initial training for 4-6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality. Several force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw mechanical allodynia by task week 12. Although not consistent in all tissues, we found several significant interactions between the critical musculoskeletal risk factors of force and repetition, consistent with a fatigue failure process in musculoskeletal tissues. Prolonged performance of HRHF tasks exhibited significantly increased risk for musculoskeletal disorders, while performance of moderate level tasks exhibited adaptation to task demands.

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.

Why we should care about soft tissue interfaces when applying ultrasonic diathermy: an experimental and computer simulation study.

PubMed

Omena, Thaís Pionório; Fontes-Pereira, Aldo José; Costa, Rejane Medeiros; Simões, Ricardo Jorge; von Krüger, Marco Antônio; Pereira, Wagner Coelho de Albuquerque

2017-01-01

One goal of therapeutic ultrasound is enabling heat generation in tissue. Ultrasound application protocols typically neglect these processes of absorption and backscatter/reflection at the skin/fat, fat/muscle, and muscle/bone interfaces. The aim of this study was to investigate the heating process at interfaces close to the transducer and the bone with the aid of computer simulation and tissue-mimicking materials (phantoms). The experimental setup consists of physiotherapeutic ultrasound equipment for irradiation, two layers of soft tissue-mimicking material, and one with and one without an additional layer of bone-mimicking material. Thermocouple monitoring is used in both cases. A computational model is used with the experimental parameters in a COMSOL® software platform. The experimental results show significant temperature rise (42 °C) at 10 mm depth, regardless of bone layer presence, diverging 3 °C from the simulated values. The probable causes are thermocouple and transducer heating and interface reverberations. There was no statistical difference in the experimental results with and without the cortical bone for the central thermocouple of the first interface [ t (38) = -1.52; 95% CI = -0.85, 0.12; p  = 14]. Temperature rise (>6 °C) close to the bone layer was lower than predicted (>21 °C), possibly because without the bone layer, thermocouples at 30 mm make contact with the water bath and convection intensifies heat loss; this factor was omitted in the simulation model. This work suggests that more attention should be given to soft tissue layer interfaces in ultrasound therapeutic procedures even in the absence of a close bone layer.

In vivo analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone.

PubMed

Abshagen, K; Schrodi, I; Gerber, T; Vollmar, B

2009-11-01

One of the major challenges in the application of bone substitutes is adequate vascularization and biocompatibility of the implant. Thus, the temporal course of neovascularization and the microvascular inflammatory response of implants of NanoBone (fully synthetic nanocrystalline bone grafting material) were studied in vivo by using the mouse dorsal skinfold chamber model. Angiogenesis, microhemodynamics, and leukocyte-endothelial cell interaction were analyzed repetitively after implantation in the center and in the border zone of the implant up to 15 days. Both NanoBone granules and plates exhibited high biocompatibility comparable to that of cancellous bone, as indicated by a lack of venular leukocyte activation after implantation. In both synthetic NanoBone groups, signs of angiogenesis could be observed even at day 5 after implantation, whereas granules showed higher functional vessel density compared with NanoBone plates. The angiogenic response of the cancellous bone was markedly accelerated in the center of the implant tissue. Histologically, implant tissue showed an ingrowth of vascularized fibrous tissue into the material combined with an increased number of foreign-body giant cells. In conclusion, NanoBone, particularly in granular form, showed high biocompatibility and high angiogenic response, thus improving the healing of bone defects. Our results underline that, beside the composition and nanostructure, the macrostructure is also of importance for the incorporation of the biomaterial by the host tissue. (c) 2008 Wiley Periodicals, Inc.

The relation of microdamage to fracture and material property degradation in human cortical bone tissue

NASA Astrophysics Data System (ADS)

Akkus, Ozan

This dissertation investigates the relation of microdamage to fracture and material property degradation of human cortical bone tissue. Fracture resistance and fatigue crack growth of microcracks were examined experimentally and material property degradation was examined through theoretical modeling. To investigate the contribution of microdamage to static fracture resistance, fracture toughness tests were conducted in the transverse and longitudinal directions to the osteonal orientation of normal bone tissue. Damage accumulation was monitored by acoustic emission during testing and was spatially observed by histological observation following testing. The results suggested that the propagation of the main crack involved weakening of the tissue by diffuse damage at the fracture plane and by formation of linear microcracks away from the fracture plane for the transverse specimens. For the longitudinal specimens, growth of the main crack occurred in the form of separations at lamellar interfaces. Acoustic emission results supported the histological observations. To investigate the contribution of ultrastructure to static fracture resistance, fracture toughness tests were conducted after altering the collagen phase of the bone tissue by gamma radiation. A significant decrease in the fracture toughness, Work-to-Fracture and the amount damage was observed due to irradiation in both crack growth directions. For cortical bone irradiated at 27.5kGy, fracture toughness is reduced due to the inhibition of damage formation at and near the crack tip. Microcrack fatigue crack growth and arrest were investigated through observations of surface cracks during cyclic loading. At the applied cyclic stresses, the microcracks propagated and arrested in less than 10,000 cycles. In addition, the microcracks were observed not to grow beyond a length of 150mum and a DeltaK of 0.5MNm-3/2, supporting a microstructural barrier concept. Finally, the contribution of linear microcracks to material property degradation was examined by developing a theoretical micromechanical damage model. The model was compared to experimentally induced damage in bone tissue. The percent contribution of linear microcracks to the total degradation was predicted to be less than 5%, indicating that diffuse damage or an unidentified form of damage is primarily responsible for material property degradation in human cortical bone tissue.

The osteoplastic effectiveness of the implants made of mesh titanium nickelide constructs.

PubMed

Mikhailovich Irianov, Iurii; Vladimirovna Diuriagina, Olga; Iurevna Karaseva, Tatiana; Anatolevich Karasev, Evgenii

2014-02-01

The purpose of the work was to study the features of reparative osteogenesis for filling the defect of tubular bone under implantation of mesh titanium nickelide constructs. Tibial fenestrated defect was modeled experimentally in 30 Wistar pubertal rats, followed by implant intramedullary insertion. The techniques of radiography, scanning electron microscopy and X-ray electron probe microanalysis were used. The mesh implant of titanium nickelide has been established to possess biocompatibility, osteoconductive and osteoinductive properties, the zone of osteogenesis and angiogenesis is created around it, bone cover is formed. Osteointegration of the implant occurs early, by 7 days after surgery, and by 30 days after surgery organotypical re-modelling of the regenerated bone takes place, as well as the defect is filled with lamellar bone tissue by the type of bone wound primary adhesion. By 30 days after surgery mineral content of the regenerated bone tissue approximates to the composition of intact cortex mineral phase.

Carbon Nanoparticle Enhance Photoacoustic Imaging and Therapy for Bone Tissue Engineering

NASA Astrophysics Data System (ADS)

Talukdar, Yahfi

Healing critical sized bone defects has been a challenge that led to innovations in tissue engineering scaffolds and biomechanical stimulations that enhance tissue regeneration. Carbon nanocomposite scaffolds have gained interest due to their enhanced mechanical properties. However, these scaffolds are only osteoconductive and not osteoinductive. Stimulating regeneration of bone tissue, osteoinductivity, has therefore been a subject of intense research. We propose the use of carbon nanoparticle enhanced photoacoustic (PA) stimulation to promote and enhance tissue regeneration in bone tissue-engineering scaffolds. In this study we test the feasibility of using carbon nanoparticles and PA for in vivo tissue engineering applications. To this end, we investigate 1) the effect of carbon nanoparticles, such as graphene oxide nanoplatelets (GONP), graphene oxide nano ribbons (GONR) and graphene nano onions (GNO), in vitro on mesenchymal stem cells (MSC), which are crucial for bone regeneration; 2) the use of PA imaging to detect and monitor tissue engineering scaffolds in vivo; and 3) we demonstrate the potential of carbon nanoparticle enhanced PA stimulation to promote tissue regeneration and healing in an in vivo rat fracture model. The results from these studies demonstrate that carbon nanoparticles such as GNOP, GONR and GNO do not affect viability or differentiation of MSCs and could potentially be used in vivo for tissue engineering applications. Furthermore, PA imaging can be used to detect and longitudinally monitor subcutaneously implanted carbon nanotubes incorporated polymeric nanocomposites in vivo. Oxygen saturation data from PA imaging could also be used as an indicator for tissue regeneration within the scaffolds. Lastly, we demonstrate that daily stimulation with carbon nanoparticle enhanced PA increases bone fracture healing. Rats stimulated for 10 minutes daily for two weeks showed 3 times higher new cortical bone BV/TV and 1.8 times bone mineral density, compared to non-stimulated controls. The results taken together indicate that carbon nanoparticle enhanced PA stimulation serves as an anabolic stimulus for bone regeneration. The results suggest opportunities towards the development of implant device combination therapies for bone loss due to disease or trauma.

Fixation Strength of Polyetheretherketone Sheath-and-Bullet Device for Soft Tissue Repair in the Foot and Ankle.

PubMed

Christensen, Jay; Fischer, Brian; Nute, Michael; Rizza, Robert

Tendon transfers are often performed in the foot and ankle. Recently, interference screws have been a popular choice owing to their ease of use and fixation strength. Considering the benefits, one disadvantage of such devices is laceration of the soft tissues by the implant threads during placement that potentially weaken the structural integrity of the grafts. A shape memory polyetheretherketone bullet-in-sheath tenodesis device uses circumferential compression, eliminating potential damage from thread rotation and maintaining the soft tissue orientation of the graft. The aim of this study was to determine the pullout strength and failure mode for this device in both a synthetic bone analogue and porcine bone models. Thirteen mature bovine extensor tendons were secured into ten 4.0 × 4.0 × 4.0-cm cubes of 15-pound per cubic foot solid rigid polyurethane foam bone analogue models or 3 porcine femoral condyles using the 5 × 20-mm polyetheretherketone soft tissue anchor. The bullet-in-sheath device demonstrated a mean pullout of 280.84 N in the bone analog models and 419.47 N in the porcine bone models. (p = .001). The bullet-in-sheath design preserved the integrity of the tendon graft, and none of the implants dislodged from their original position. Copyright © 2017 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Overdenture retaining bar stress distribution: a finite-element analysis.

PubMed

Caetano, Conrado Reinoldes; Mesquita, Marcelo Ferraz; Consani, Rafael Leonardo Xediek; Correr-Sobrinho, Lourenço; Dos Santos, Mateus Bertolini Fernandes

2015-05-01

Evaluate the stress distribution on the peri-implant bone tissue and prosthetic components of bar-clip retaining systems for overdentures presenting different implant inclinations, vertical misfit and framework material. Three-dimensional models of a jaw and an overdenture retained by two implants and a bar-clip attachment were modeled using specific software (SolidWorks 2010). The studied variables were: latero-lateral inclination of one implant (-10°, -5°, 0°, +5°, +10°); vertical misfit on the other implant (50, 100, 200 µm); and framework material (Au type IV, Ag-Pd, Ti cp, Co-Cr). Solid models were imported into mechanical simulation software (ANSYS Workbench 11). All nodes on the bone's external surface were constrained and a displacement was applied to simulate the settling of the framework on the ill-fitted component. Von Mises stress for the prosthetic components and maximum principal stress to the bone tissue were evaluated. The +10° inclination presented the worst biomechanical behavior, promoting the highest stress values on the bar framework and peri-implant bone tissue. The -5° group presented the lowest stress values on the prosthetic components and the lowest stress value on peri-implant bone tissue was observed in -10°. Increased vertical misfit caused an increase on the stress values in all evaluated structures. Stiffer framework materials caused a considerable stress increase in the framework itself, prosthetic screw of the fitted component and peri-implant bone tissue. Inclination of one implant associated with vertical misfit caused a relevant effect on the stress distribution in bar-clip retained overdentures. Different framework materials promoted increased levels of stress in all the evaluated structures.

Intra-oral soft tissue expansion and volume stability of onlay bone grafts.

PubMed

Abrahamsson, Peter

2011-01-01

Insufficient regeneration of missing bone and soft-tissue may present aesthetic or functional problems in patients indicated for dental implant surgery. Several techniques such as bone grafts, bone substitutes and guided tissue regeneration (GTR) have been described to rebuild a compromised alveolar ridge. Adequate soft-tissue coverage of grafted bone and titanium-mesh is important to avoid exposure which may result in loss of the bone graft. The general aim of this thesis was to evaluate use of an osmotic tissue expander for expanding intra-oral soft tissue--creating a surplus of soft tissue-- in preparation for onlay bone grafting. An experimental rabbit model was used in studies (I), (II) and (III). In (I) an osmotic soft-tissue expander was placed bilaterally on the lateral wall of the mandible via an extra-oral approach. After two weeks of expansion the rabbits were killed and specimens were collected for histology. No inflammatory reaction and no resorbtion of the cortical bone occured. The periosteum was expanded and new bone formation was seen in the edges of the expander. In (II) and (III) the expander was placed under the periosteum in the same way as in (I): bilaterally in 13 rabbits in (II) and unilaterally in 11 rabbits in (III). After two weeks of expansion the expander was identified and removed. In (II) particulated bone was placed at the recipient site protected by a titanium mesh in one site and a bio-resorbable mesh on the other site. In (III), DBBM particles and bone particles collected from the lateral border of the mandible separated by a collagen membrane was placed at the recipient site. The graft was protected by a pre-bent titanium mesh covered by a collagen membrane. After a healing period of 3 months specimens were collected for histological and SEM examination. New bone was growing in direct contact with the titanium mesh and bio resorbable mesh. The newly formed bone had the same calcium content as the mature bone in the base of the mandible. In the clinical study (IV) 20 patients were consecutively recruited and randomised into two groups. The experimental group (ten patients) had an osmotic soft tissue expander implanted. After two weeks of expansion the expander was removed and a particulated bone graft protected by a titanium mesh and a collagen membrane was fixed to the recipient site. Titanium implants were installed after a healing period of 6 months. The patients in the reference group had a bone block grafted from the anterior ramus fixated to the recipient site with one or two titanium mini screws. Implants were installed after a healing period of 6 months. A three dimensional optical measuring device was used to measure alterations in the soft tissue profile before each surgical procedure. The three-dimensional changes were then analysed on a PC. The results from the clinical study in patients confirmed the results from the experimental rabbit studies. The osmotic tissue expander expanded the soft tissue. Expander perforations of the soft tissue occurred in two patients. The optical measurements demonstrated a positive volume gain after soft tissue expansion and bone grafting. The expanded tissue could be used to cover a bone graft. There still was a risk of mesh exposure, even after soft tissue expansion, which occurred in two patients. In both groups, implants could be installed in the grafted bone in positions that would allow the crowns to fit aesthetically into the dental arch.

Localized tissue mineralization regulated by bone remodelling: A computational approach

PubMed Central

Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

2017-01-01

Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

Coupling multiscale X-ray physics and micromechanics for bone tissue composition and elasticity determination from micro-CT data, by example of femora from OVX and sham rats

NASA Astrophysics Data System (ADS)

Hasslinger, Patricia; Vass, Viktoria; Dejaco, Alexander; Blanchard, Romane; Örlygsson, Gissur; Gargiulo, Paolo; Hellmich, Christian

2016-05-01

Due to its high resolution, micro-CT (Computed Tomograph) scanning is the key to assess bone quality of sham and OVX (ovariectomized) rats. Combination of basic X-ray physics, such as the energy- and chemistry-dependence of attenuation coefficients, with results from ashing tests on rat bones, delivers mineral, organic, and water volume fractions within the voxels. Additional use of a microelastic model for bone provides voxel-specific elastic properties. The new method delivers realistic bone mass densities, and reveals that OVX protocols may indeed induce some bone mass loss, while the average composition of the bone tissue remains largely unaltered.

INCREASING DURATION OF TYPE 1 DIABETES PERTURBS THE STRENGTH-STRUCTURE RELATIONSHIP AND INCREASES BRITTLENESS OF BONE

PubMed Central

Nyman, Jeffry S.; Even, Jesse L.; Jo, Chan-Hee; Herbert, Erik G.; Murry, Matthew R.; Cockrell, Gael E.; Wahl, Elizabeth C.; Bunn, R. Clay; Lumpkin, Charles K.; Fowlkes, John L.; Thrailkill, Kathryn M.

2011-01-01

Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18 weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (IMIN) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by microcomputed tomography and 2) biomechanical properties by three point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, IMIN, rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then IMIN would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and IMIN depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these findings suggest that the elevated fracture risk among diabetics is impacted by complex changes in tissue properties that ultimately reduce the fracture resistance of bone. PMID:21185416

Dynamic Bioreactor Culture of High Volume Engineered Bone Tissue

PubMed Central

Nguyen, Bao-Ngoc B.; Ko, Henry; Moriarty, Rebecca A.; Etheridge, Julie M.

2016-01-01

Within the field of tissue engineering and regenerative medicine, the fabrication of tissue grafts of any significant size—much less a whole organ or tissue—remains a major challenge. Currently, tissue-engineered constructs cultured in vitro have been restrained in size primarily due to the diffusion limit of oxygen and nutrients to the center of these grafts. Previously, we developed a novel tubular perfusion system (TPS) bioreactor, which allows the dynamic culture of bead-encapsulated cells and increases the supply of nutrients to the entire cell population. More interestingly, the versatility of TPS bioreactor allows a large range of engineered tissue volumes to be cultured, including large bone grafts. In this study, we utilized alginate-encapsulated human mesenchymal stem cells for the culture of a tissue-engineered bone construct in the size and shape of the superior half of an adult human femur (∼200 cm3), a 20-fold increase over previously reported volumes of in vitro engineered bone grafts. Dynamic culture in TPS bioreactor not only resulted in high cell viability throughout the femur graft, but also showed early signs of stem cell differentiation through increased expression of osteogenic genes and proteins, consistent with our previous models of smaller bone constructs. This first foray into full-scale bone engineering provides the foundation for future clinical applications of bioengineered bone grafts. PMID:26653703

Visualizing Angiogenesis by Multiphoton Microscopy In Vivo in Genetically Modified 3D-PLGA/nHAp Scaffold for Calvarial Critical Bone Defect Repair.

PubMed

Li, Jian; Jahr, Holger; Zheng, Wei; Ren, Pei-Gen

2017-09-07

The reconstruction of critically sized bone defects remains a serious clinical problem because of poor angiogenesis within tissue-engineered scaffolds during repair, which gives rise to a lack of sufficient blood supply and causes necrosis of the new tissues. Rapid vascularization is a vital prerequisite for new tissue survival and integration with existing host tissue. The de novo generation of vasculature in scaffolds is one of the most important steps in making bone regeneration more efficient, allowing repairing tissue to grow into a scaffold. To tackle this problem, the genetic modification of a biomaterial scaffold is used to accelerate angiogenesis and osteogenesis. However, visualizing and tracking in vivo blood vessel formation in real-time and in three-dimensional (3D) scaffolds or new bone tissue is still an obstacle for bone tissue engineering. Multiphoton microscopy (MPM) is a novel bio-imaging modality that can acquire volumetric data from biological structures in a high-resolution and minimally-invasive manner. The objective of this study was to visualize angiogenesis with multiphoton microscopy in vivo in a genetically modified 3D-PLGA/nHAp scaffold for calvarial critical bone defect repair. PLGA/nHAp scaffolds were functionalized for the sustained delivery of a growth factor pdgf-b gene carrying lentiviral vectors (LV-pdgfb) in order to facilitate angiogenesis and to enhance bone regeneration. In a scaffold-implanted calvarial critical bone defect mouse model, the blood vessel areas (BVAs) in PHp scaffolds were significantly higher than in PH scaffolds. Additionally, the expression of pdgf-b and angiogenesis-related genes, vWF and VEGFR2, increased correspondingly. MicroCT analysis indicated that the new bone formation in the PHp group dramatically improved compared to the other groups. To our knowledge, this is the first time multiphoton microscopy was used in bone tissue-engineering to investigate angiogenesis in a 3D bio-degradable scaffold in vivo and in real-time.

Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep.

PubMed

Weiler, Andreas; Hoffmann, Reinhard F G; Bail, Hermann J; Rehm, Oliver; Südkamp, Norbert P

2002-02-01

Tendon-to-bone healing of soft-tissue grafts has been described to progress by the development of a fibrous interzone that undergoes a maturation process leading to the development of an indirect type of ligament insertion. Previous studies used extra-articular models or fixation far away from the joint line; thus, no data are available investigating tendon-to-bone healing of a soft-tissue graft fixed anatomically. Therefore, we studied the tendon-to-bone healing of the anatomic soft-tissue graft interference fit fixation in a model of anterior cruciate ligament (ACL) reconstruction in sheep. Animal study. Thirty-five mature sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. Grafts were directly fixed with biodegradable poly-(D,L-lactide) interference screws. Animals were euthanized after 6, 9, 12, 24, and 52 weeks and histologic evaluations were performed. Undecalcified specimens were evaluated under normal and polarized light. Additionally, animals received a polychrome sequential labeling (tetracycline, xylenol orange, and calcein green) to determine bone growth per time under fluorescent light. Intratunnel histologic findings at 6 weeks showed a tendon-bone junction with only a partial fibrous interzone between the graft tissue and the surrounding bone. A mature intratunnel tendon-bone junction with a zone of fibrocartilage was found at 9 to 12 weeks. At the tunnel entrance site a wide regular ligamentous insertion site was seen in all specimens after 24 weeks. This insertion showed regular patterns such as the direct type of insertion of a normal ligament with a dense basophilic transition zone consisting of mineralized cartilage. A fibrous interzone between the graft tissue and the bone tunnel was only partially developed, which is in contrast to all previous studies in which nonanatomic fixation was used. Thus, it is reasonable to assume that the tendon-to-bone healing in the present study may progress partially by direct-contact healing without the development of a fibrous interzone. To our knowledge, this is the first report describing the development of a direct type of ligament insertion after ACL replacement with a soft-tissue graft. This is in contrast to previous studies reporting the development of an indirect type of insertion when using nonanatomic fixation far away from the joint line. Thus, histologic data strongly indicate that anatomic interference fit fixation is beneficial for tendon-to-bone incorporation by leading to the development of a direct type of ligament insertion.

Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

PubMed

Cruel, M; Granke, M; Bosser, C; Audran, M; Hoc, T

2017-06-01

Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dose equivalent near the bone-soft tissue interface from nuclear fragments produced by high-energy protons

NASA Technical Reports Server (NTRS)

Shavers, M. R.; Poston, J. W.; Cucinotta, F. A.; Wilson, J. W.

1996-01-01

During manned space missions, high-energy nucleons of cosmic and solar origin collide with atomic nuclei of the human body and produce a broad linear energy transfer spectrum of secondary particles, called target fragments. These nuclear fragments are often more biologically harmful than the direct ionization of the incident nucleon. That these secondary particles increase tissue absorbed dose in regions adjacent to the bone-soft tissue interface was demonstrated in a previous publication. To assess radiological risks to tissue near the bone-soft tissue interface, a computer transport model for nuclear fragments produced by high energy nucleons was used in this study to calculate integral linear energy transfer spectra and dose equivalents resulting from nuclear collisions of 1-GeV protons transversing bone and red bone marrow. In terms of dose equivalent averaged over trabecular bone marrow, target fragments emitted from interactions in both tissues are predicted to be at least as important as the direct ionization of the primary protons-twice as important, if recently recommended radiation weighting factors and "worst-case" geometry are used. The use of conventional dosimetry (absorbed dose weighted by aa linear energy transfer-dependent quality factor) as an appropriate framework for predicting risk from low fluences of high-linear energy transfer target fragments is discussed.

Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells.

PubMed

Li, Qinlong; Yin, Lijuan; Jones, Lawrence W; Chu, Gina C-Y; Wu, Jason B-Y; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R; Garraway, Isla; Lewis, Michael S; Chung, Leland W K; Zhau, Haiyen E

2016-12-20

Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases.

WE-E-BRE-01: An Image-Based Skeletal Dosimetry Model for the ICRP Reference Adult Female - Internal Electron Sources

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

O'Reilly, S; Maynard, M; Marshall, E

Purpose: Limitations seen in previous skeletal dosimetry models, which are still employed in commonly used software today, include the lack of consideration of electron escape and cross-fire from cortical bone, the modeling of infinite spongiosa, the disregard of the effect of varying cellularity on active marrow self-irradiation, and the lack of use of the more recent ICRP definition of a 50 micron surrogate tissue region for the osteoprogenitor cells - shallow marrow. These limitations were addressed in the present dosimetry model. Methods: Electron transport was completed to determine specific absorbed fractions to active marrow and shallow marrow of the skeletalmore » regions of the adult female. The bone macrostructure was obtained from the whole-body hybrid computational phantom of the UF series of reference phantoms, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 year-old female cadaver. The target tissue regions were active marrow and shallow marrow. The source tissues were active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume and cortical bone surfaces. The marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or modeled analytically. Results: The method of combining macro- and microstructure absorbed fractions calculated using MCNPX electron transport was found to yield results similar to those determined with the PIRT model for the UF adult male in the Hough et al. study. Conclusion: The calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) and did not follow current models used in nuclear medicine dosimetry at high energies (due to that models use of an infinite expanse of trabecular spongiosa)« less

Development of the Gecko (Pachydactylus turneri) Animal Model during Foton M-2 to Study Comparative Effects of Microgravity in Terrestrial and Aquatic Organisms

NASA Technical Reports Server (NTRS)

Almeida, E. A.; Roden, C.; Phillips, J. A.; Globus, R. K.; Searby, N.; Vercoutere, W.; Morey-Holton, E.; Gulimova, V.; Saveliev, S.; Tairbekov, M.;

Kinetic examination of femoral bone modeling in broilers.

PubMed

Prisby, R; Menezes, T; Campbell, J; Benson, T; Samraj, E; Pevzner, I; Wideman, R F

2014-05-01

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers.

Use of perfusion bioreactors and large animal models for long bone tissue engineering.

PubMed

Gardel, Leandro S; Serra, Luís A; Reis, Rui L; Gomes, Manuela E

2014-04-01

Tissue engineering and regenerative medicine (TERM) strategies for generation of new bone tissue includes the combined use of autologous or heterologous mesenchymal stem cells (MSC) and three-dimensional (3D) scaffold materials serving as structural support for the cells, that develop into tissue-like substitutes under appropriate in vitro culture conditions. This approach is very important due to the limitations and risks associated with autologous, as well as allogenic bone grafiting procedures currently used. However, the cultivation of osteoprogenitor cells in 3D scaffolds presents several challenges, such as the efficient transport of nutrient and oxygen and removal of waste products from the cells in the interior of the scaffold. In this context, perfusion bioreactor systems are key components for bone TERM, as many recent studies have shown that such systems can provide dynamic environments with enhanced diffusion of nutrients and therefore, perfusion can be used to generate grafts of clinically relevant sizes and shapes. Nevertheless, to determine whether a developed tissue-like substitute conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation, and for this reason, the use of animal models is often an essential step in the testing of orthopedic implants before clinical use in humans. This review provides an overview of the concepts, advantages, and challenges associated with different types of perfusion bioreactor systems, particularly focusing on systems that may enable the generation of critical size tissue engineered constructs. Furthermore, this review discusses some of the most frequently used animal models, such as sheep and goats, to study the in vivo functionality of bone implant materials, in critical size defects.

High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

PubMed

Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

2011-05-01

The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.

High Doses of Bone Morphogenetic Protein 2 Induce Structurally Abnormal Bone and Inflammation In Vivo

PubMed Central

Zara, Janette N.; Siu, Ronald K.; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M.; Ting, Kang

2011-01-01

The major Food and Drug Association–approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL. PMID:21247344

Regenerative Medicine for Periodontal and Peri-implant Diseases

PubMed Central

Larsson, L.; Decker, A.M.; Nibali, L.; Pilipchuk, S.P.; Berglundh, T.; Giannobile, W.V.

2015-01-01

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions. PMID:26608580

Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats.

PubMed

Ghanaati, Shahram; Orth, Carina; Barbeck, Mike; Willershausen, Ines; Thimm, Benjamin W; Booms, Patrick; Stübinger, Stefan; Landes, Constantin; Sader, Robert Anton; Kirkpatrick, Charles James

2010-06-01

The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute.The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

Bone as an effect compartment : models for uptake and release of drugs.

PubMed

Stepensky, David; Kleinberg, Lilach; Hoffman, Amnon

2003-01-01

"Bone-seeking agents" are drugs characterised by high affinity for bone, and are disposed in bone for prolonged periods of time while maintaining remarkably low systemic concentrations. As a consequence, the bone becomes a reservoir for bone-seeking agents, and a site of both desirable and adverse effects, depending on the pharmacological activities of the specific agent. For some agents, significant systemic effects may also be produced following their prolonged release from bone, a process that is governed mostly by the rate of bone remodelling. This review covers the pharmacokinetic and pharmacodynamic features of bone-seeking agents with different pharmacological properties, including drugs (bisphosphonates, drug-bisphosphonate conjugates, radiopharmaceuticals and fluoride), bone markers (tetracycline, bone imaging agents) and toxins (lead, chromium, aluminium). In addition, drugs that do not possess bone-seeking properties but are used for therapy of bone diseases (such as antibacterials for treatment of osteomyelitis) are discussed, along with targeting of these drugs to the bone by conjugation to bone-seeking agents, local delivery systems, and other approaches. The pharmacokinetic and pharmacodynamic behaviour of bone-seeking agents is extremely complex due to heterogeneity in bone morphology and physiology. This complexity, accompanied by difficulties in human bone research caused by ethical and other limitations, gave rise to modelling approaches to study bone drug disposition. This review describes the pharmacokinetic models that have been proposed to describe the pharmacokinetic behaviour of bone-seeking agents and predict bone concentrations of these agents for different doses and patient populations. Models of different types (compartmental and physiologically based) and of different complexity have been applied, but their relevance to drug effects in the bone tissue is limited since they describe the behaviour of the "average" drug molecule. Understanding of the cellular and molecular processes responsible for the heterogeneity of bone tissue will provide better comprehension of the influence of microenvironment on drug bone disposition and the resulting pharmacological response.

Osteoconductive composite graft based on bacterial synthesized hydroxyapatite nanoparticles doped with different ions: From synthesis to in vivo studies.

PubMed

Ahmadzadeh, Elham; Talebnia, Farid; Tabatabaei, Meisam; Ahmadzadeh, Hossein; Mostaghaci, Babak

2016-07-01

To repair damaged bone tissues, osteoconductive bone graft substitutes are required for enhancement of the regenerative potential of osteoblast cells. Nanostructured hydroxyapatite is a bioactive ceramic used for bone tissue engineering purposes. In this study, carbonate hydroxyapatite (cHA) and zinc-magnesium substituted hydroxyapatite (Zn-Mg-HA) nanoparticles were synthesized via biomineralization method using Enterobacter aerogenes. The structural phase composition and the morphology of the samples were analyzed using appropriate powder characterization methods. Next, a composite graft was fabricated by using polyvinyl alcohol and both cHA and Zn-Mg-HA samples. In vivo osteogenic potential of the graft was then investigated in a rabbit tibial osteotomy model. Histological, radiological and morphological studies showed that the graft was mineralized by the newly formed bone tissue without signs of inflammation or infection after 4 weeks of implantation. These histomorphometric results suggest that the fabricated graft can function as a potent osteoconductive bone tissue substitute. Copyright © 2016 Elsevier Inc. All rights reserved.

The mechanical heterogeneity of the hard callus influences local tissue strains during bone healing: a finite element study based on sheep experiments.

PubMed

Vetter, A; Liu, Y; Witt, F; Manjubala, I; Sander, O; Epari, D R; Fratzl, P; Duda, G N; Weinkamer, R

2011-02-03

During secondary fracture healing, various tissue types including new bone are formed. The local mechanical strains play an important role in tissue proliferation and differentiation. To further our mechanobiological understanding of fracture healing, a precise assessment of local strains is mandatory. Until now, static analyses using Finite Elements (FE) have assumed homogenous material properties. With the recent quantification of both the spatial tissue patterns (Vetter et al., 2010) and the development of elastic modulus of newly formed bone during healing (Manjubala et al., 2009), it is now possible to incorporate this heterogeneity. Therefore, the aim of this study is to investigate the effect of this heterogeneity on the strain patterns at six successive healing stages. The input data of the present work stemmed from a comprehensive cross-sectional study of sheep with a tibial osteotomy (Epari et al., 2006). In our FE model, each element containing bone was described by a bulk elastic modulus, which depended on both the local area fraction and the local elastic modulus of the bone material. The obtained strains were compared with the results of hypothetical FE models assuming homogeneous material properties. The differences in the spatial distributions of the strains between the heterogeneous and homogeneous FE models were interpreted using a current mechanobiological theory (Isakson et al., 2006). This interpretation showed that considering the heterogeneity of the hard callus is most important at the intermediate stages of healing, when cartilage transforms to bone via endochondral ossification. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Effect of vascular endothelial growth factor and tumor necrosis factor receptor for treatment of avascular necrosis of the femoral head in rabbits].

PubMed

Hu, Zhi-ming; Zhou, Ming-qian; Gao, Ji-min

2008-12-01

To evaluate the therapeutic effect of vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of the femoral head in rabbits. Avascular necrosis of the femoral head was induced in 26 New Zealand white rabbits by injections of horse serum and prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF treatment group, and untreated model group, with another 4 normal rabbits as the normal control group. In the two treatment groups, the therapeutic agents were injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay was performed to determine the concentration of TNF-alpha in rabbit serum followed by pathological examination of the changes in the bone tissues, bone marrow hematopoietic tissue and the blood vessels in the femoral head. Compared with the model group, the rabbits with both VEGF and TNFR treatment showed decreased serum concentration of TNF-alpha with obvious new vessel formation, decreased empty bone lacunae in the femoral head and hematopoietic tissue proliferation in the bone marrow cavity. Percutaneous injection of VEGF and TNFR into the femoral head can significantly enhance bone tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental femoral head necrosis.

Microgravity Stress: Bone and Connective Tissue.

PubMed

Bloomfield, Susan A; Martinez, Daniel A; Boudreaux, Ramon D; Mantri, Anita V

2016-03-15

The major alterations in bone and the dense connective tissues in humans and animals exposed to microgravity illustrate the dependency of these tissues' function on normal gravitational loading. Whether these alterations depend solely on the reduced mechanical loading of zero g or are compounded by fluid shifts, altered tissue blood flow, radiation exposure, and altered nutritional status is not yet well defined. Changes in the dense connective tissues and intervertebral disks are generally smaller in magnitude but occur more rapidly than those in mineralized bone with transitions to 0 g and during recovery once back to the loading provided by 1 g conditions. However, joint injuries are projected to occur much more often than the more catastrophic bone fracture during exploration class missions, so protecting the integrity of both tissues is important. This review focuses on the research performed over the last 20 years in humans and animals exposed to actual spaceflight, as well as on knowledge gained from pertinent ground-based models such as bed rest in humans and hindlimb unloading in rodents. Significant progress has been made in our understanding of the mechanisms for alterations in bone and connective tissues with exposure to microgravity, but intriguing questions remain to be solved, particularly with reference to biomedical risks associated with prolonged exploration missions. Copyright © 2016 John Wiley & Sons, Inc.

Bare Bones of Bioactive Glass

NASA Technical Reports Server (NTRS)

2000-01-01

Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Even in normal gravity, bioactive glass particles enhance bone growth in laboratory tests with flat tissue cultures. Ducheyne and his team believe that using the bioactive microcarriers in a rotating bioreactor in microgravity will produce improved, three-dimensional tissue cultures. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: NASA and University of Pennsylvania Center for Bioactive Materials and Tissue Engineering.

Using the Abitibi Greenstone Belt to Understand Martian Hydrothermal Systems and the Potential for Biosignature Preservation in High Temperature Aqueous Environments

NASA Technical Reports Server (NTRS)

Hurowitz, J.; Abelson, J.; Allwood, A.; Anderson, R.; Atkinson, B.; Beaty, D.; Bristow, T.; Ehlmann, B.; Eigenbrode, J.; Grotzinger, J.;

Role of sediment size and biostratinomy on the development of biofilms in recent avian vertebrate remains

NASA Astrophysics Data System (ADS)

Peterson, Joseph E.; Lenczewski, Melissa E.; Clawson, Steven R.; Warnock, Jonathan P.

2017-04-01

Microscopic soft tissues have been identified in fossil vertebrate remains collected from various lithologies. However, the diagenetic mechanisms to preserve such tissues have remained elusive. While previous studies have described infiltration of biofilms in Haversian and Volkmann’s canals, biostratinomic alteration (e.g., trampling), and iron derived from hemoglobin as playing roles in the preservation processes, the influence of sediment texture has not previously been investigated. This study uses a Kolmogorov Smirnov Goodness-of-Fit test to explore the influence of biostratinomic variability and burial media against the infiltration of biofilms in bone samples. Controlled columns of sediment with bone samples were used to simulate burial and subsequent groundwater flow. Sediments used in this study include clay-, silt-, and sand-sized particles modeled after various fluvial facies commonly associated with fossil vertebrates. Extant limb bone samples obtained from Gallus gallus domesticus (Domestic Chicken) buried in clay-rich sediment exhibit heavy biofilm infiltration, while bones buried in sands and silts exhibit moderate levels. Crushed bones exhibit significantly lower biofilm infiltration than whole bone samples. Strong interactions between biostratinomic alteration and sediment size are also identified with respect to biofilm development. Sediments modeling crevasse splay deposits exhibit considerable variability; whole-bone crevasse splay samples exhibit higher frequencies of high-level biofilm infiltration, and crushed-bone samples in modeled crevasse splay deposits display relatively high frequencies of low-level biofilm infiltration. These results suggest that sediment size, depositional setting, and biostratinomic condition play key roles in biofilm infiltration in vertebrate remains, and may influence soft tissue preservation in fossil vertebrates.

Tissue engineering in periodontal tissue.

PubMed

Iwata, Takanori; Yamato, Masayuki; Ishikawa, Isao; Ando, Tomohiro; Okano, Teruo

2014-01-01

Periodontitis, a recognized disease worldwide, is bacterial infection-induced inflammation of the periodontal tissues that results in loss of alveolar bone. Once it occurs, damaged tissue cannot be restored to its original form, even if decontaminating treatments are performed. For more than half a century, studies have been conducted to investigate true periodontal regeneration. Periodontal regeneration is the complete reconstruction of the damaged attachment apparatus, which contains both hard tissue (alveolar bone and cementum) and soft tissue (periodontal ligament). Several treatments, including bone grafts, guided tissue regeneration with physical barriers for epithelial cells, and growth factors have been approved for clinical use; however, their indications and outcomes are limited. To overcome these limitations, the concept of "tissue engineering" was introduced. Combination treatment using cells, growth factors, and scaffolds, has been studied in experimental animal models, and some studies have been translated into clinical trials. In this review, we focus on recent progressive tissue engineering studies and discuss future perspectives on periodontal regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with Osteogenesis Imperfecta

PubMed Central

Jameson, John; Smith, Peter; Harris, Gerald

2015-01-01

Osteogenesis Imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64–68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3–42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (p≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight towards understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta. PMID:24928496

Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

PubMed

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

2014-09-01

Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3 and 42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (P≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta. Copyright © 2014 Elsevier Inc. All rights reserved.

Infrared imaging microscopy of bone: Illustrations from a mouse model of Fabry disease

PubMed Central

Boskey, Adele L.; Goldberg, Michel; Kulkarni, Ashok; Gomez, Santiago

2006-01-01

Bone is a complex tissue whose composition and properties vary with age, sex, diet, tissue type, health and disease. In this review, we demonstrate how infrared spectroscopy and infrared spectroscopic imaging can be applied to the study of these variations. A specific example of mice with Fabry disease (a lipid storage disease) is presented in which it is demonstrated that the bones of these young animals, while showing typical spatial variation in mineral content, mineral crystal size, and collagen maturity, do not differ from the bones of age- and sex-matched wild type animals. PMID:16697974

Infrared imaging microscopy of bone: illustrations from a mouse model of Fabry disease.

PubMed

Boskey, Adele L; Goldberg, Michel; Kulkarni, Ashok; Gomez, Santiago

2006-07-01

Bone is a complex tissue whose composition and properties vary with age, sex, diet, tissue type, health and disease. In this review, we demonstrate how infrared spectroscopy and infrared spectroscopic imaging can be applied to the study of these variations. A specific example of mice with Fabry disease (a lipid storage disease) is presented in which it is demonstrated that the bones of these young animals, while showing typical spatial variation in mineral content, mineral crystal size, and collagen maturity, do not differ from the bones of age- and sex-matched wild type animals.

In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials.

PubMed

Dai, Zhenyu; Li, Yue; Lu, Weizhong; Jiang, Dianming; Li, Hong; Yan, Yonggang; Lv, Guoyu; Yang, Aiping

2015-01-01

To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) complex biomaterials with muscle and bone tissue in an in vivo model. Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE) staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM) at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining. HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that the peripheral tissues of the implanted biomaterials were continuous and lacked bone osteolysis, absorption, necrosis, or osteomyelitis. The connection between implanted biomaterials and bone tissue was tight. The results of HE, Masson, toluidine blue staining and SEM confirmed that the implanted biomaterials were closely connected to the bone defect and that no rejection had taken place. The n-CDHA/PAA biomaterials induced differentiation of a large number of chondrocytes. New bone trabecula began to form at 4 weeks after implanting n-CDHA/PAA biomaterials, and lamellar bone gradually formed at 12 weeks and 24 weeks after implantation. Routine blood and kidney function tests showed no significant changes at 2 weeks and 24 weeks after implantation of both biomaterials. n-CDHA/PAA composites showed good compatibility in in vivo model. In this study, n-CDHA/PAA were found to be safe, nontoxic, and biologically active in bone repair.

In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials

PubMed Central

Dai, Zhenyu; Li, Yue; Lu, Weizhong; Jiang, Dianming; Li, Hong; Yan, Yonggang; Lv, Guoyu; Yang, Aiping

2015-01-01

Objective To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) complex biomaterials with muscle and bone tissue in an in vivo model. Methods Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE) staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM) at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining. Results HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that the peripheral tissues of the implanted biomaterials were continuous and lacked bone osteolysis, absorption, necrosis, or osteomyelitis. The connection between implanted biomaterials and bone tissue was tight. The results of HE, Masson, toluidine blue staining and SEM confirmed that the implanted biomaterials were closely connected to the bone defect and that no rejection had taken place. The n-CDHA/PAA biomaterials induced differentiation of a large number of chondrocytes. New bone trabecula began to form at 4 weeks after implanting n-CDHA/PAA biomaterials, and lamellar bone gradually formed at 12 weeks and 24 weeks after implantation. Routine blood and kidney function tests showed no significant changes at 2 weeks and 24 weeks after implantation of both biomaterials. Conclusion n-CDHA/PAA composites showed good compatibility in in vivo model. In this study, n-CDHA/PAA were found to be safe, nontoxic, and biologically active in bone repair. PMID:26504382

Platform switching: biomechanical evaluation using three-dimensional finite element analysis.

PubMed

Tabata, Lucas Fernando; Rocha, Eduardo Passos; Barão, Valentim Adelino Ricardo; Assunção, Wirley Goncalves

2011-01-01

The objective of this study was to evaluate, using three-dimensional finite element analysis (3D FEA), the stress distribution in peri-implant bone tissue, implants, and prosthetic components of implant-supported single crowns with the use of the platform-switching concept. Three 3D finite element models were created to replicate an external-hexagonal implant system with peri-implant bone tissue in which three different implant-abutment configurations were represented. In the regular platform (RP) group, a regular 4.1-mm-diameter abutment (UCLA) was connected to regular 4.1-mm-diameter implant. The platform-switching (PS) group was simulated by the connection of a wide implant (5.0 mm diameter) to a regular 4.1-mm-diameter UCLA abutment. In the wide-platform (WP) group, a 5.0-mm-diameter UCLA abutment was connected to a 5.0-mm-diameter implant. An occlusal load of 100 N was applied either axially or obliquely on the models using ANSYS software. Both the increase in implant diameter and the use of platform switching played roles in stress reduction. The PS group presented lower stress values than the RP and WP groups for bone and implant. In the peri-implant area, cortical bone exhibited a higher stress concentration than the trabecular bone in all models and both loading situations. Under oblique loading, higher intensity and greater distribution of stress were observed than under axial loading. Platform switching reduced von Mises (17.5% and 9.3% for axial and oblique loads, respectively), minimum (compressive) (19.4% for axial load and 21.9% for oblique load), and maximum (tensile) principal stress values (46.6% for axial load and 26.7% for oblique load) in the peri-implant bone tissue. Platform switching led to improved biomechanical stress distribution in peri-implant bone tissue. Oblique loads resulted in higher stress concentrations than axial loads for all models. Wide-diameter implants had a large influence in reducing stress values in the implant system.

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.

Stimulation of angiogenesis, neurogenesis and regeneration by side population cells from dental pulp.

PubMed

Ishizaka, Ryo; Hayashi, Yuki; Iohara, Koichiro; Sugiyama, Masahiko; Murakami, Masashi; Yamamoto, Tsubasa; Fukuta, Osamu; Nakashima, Misako

2013-03-01

Mesenchymal stem cells (MSCs) have been used for cell therapy in various experimental disease models. However, the regenerative potential of MSCs from different tissue sources and the influence of the tissue niche have not been investigated. In this study, we compared the regenerative potential of dental pulp, bone marrow and adipose tissue-derived CD31(-) side population (SP) cells isolated from an individual porcine source. Pulp CD31(-) SP cells expressed the highest levels of angiogenic/neurotrophic factors and had the highest migration activity. Conditioned medium from pulp CD31(-) SP cells produced potent anti-apoptotic activity and neurite outgrowth, compared to those from bone marrow and adipose CD31(-) SP cells. Transplantation of pulp CD31(-) SP cells in a mouse hindlimb ischemia model produced higher blood flow and capillary density than transplantation of bone marrow and adipose CD31(-) SP cells. Motor function recovery and infarct size reduction were greater with pulp CD31(-) SP cells. Pulp CD31(-) SP cells induced maximal angiogenesis, neurogenesis and pulp regeneration in ectopic transplantation models compared to other tissue sources. These results demonstrate that pulp stem cells have higher angiogenic, neurogenic and regenerative potential and may therefore be superior to bone marrow and adipose stem cells for cell therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bone marrow-resident NK cells prime monocytes for regulatory function during infection

PubMed Central

Askenase, Michael H.; Han, Seong-Ji; Byrd, Allyson L.; da Fonseca, Denise Morais; Bouladoux, Nicolas; Wilhelm, Christoph; Konkel, Joanne E.; Hand, Timothy W.; Lacerda-Queiroz, Norinne; Su, Xin-Zhuan; Trinchieri, Giorgio; Grainger, John R.; Belkaid, Yasmine

2015-01-01

SUMMARY Tissue-infiltrating Ly6Chi monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DC) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals following tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function. PMID:26070484

Retention System and Splinting on Morse Taper Implants in the Posterior Maxilla by 3D Finite Element Analysis.

PubMed

Lemos, Cleidiel Aparecido Araujo; Verri, Fellippo Ramos; Santiago, Joel Ferreira; Almeida, Daniel Augusto de Faria; Batista, Victor Eduardo de Souza; Noritomi, Pedro Yoshito; Pellizzer, Duardo Piza

2018-01-01

The purpose of this study was to evaluate different retention systems (cement- or screw-retained) and crown designs (non-splinted or splinted) of fixed implant-supported restorations, in terms of stress distributions in implants/components and bone tissue, by 3-dimensional (3D) finite element analysis. Four 3D models were simulated with the InVesalius, Rhinoceros 3D, and SolidWorks programs. Models were made of type III bone from the posterior maxillary area. Models included three 4.0-mm-diameter Morse taper (MT) implants with different lengths, which supported metal-ceramic crowns. Models were processed by the Femap and NeiNastran programs, using an axial force of 400 N and oblique force of 200 N. Results were visualized as the von Mises stress and maximum principal stress (σmax). Under axial loading, there was no difference in the distribution of stress in implants/components between retention systems and splinted crowns; however, in oblique loading, cemented prostheses showed better stress distribution than screwed prostheses, whereas splinted crowns tended to reduce stress in the implant of the first molar. In the bone tissue cemented prostheses showed better stress distribution in bone tissue than screwed prostheses under axial and oblique loading. The splinted design only had an effect in the screwed prosthesis, with no influence in the cemented prosthesis. Cemented prostheses on MT implants showed more favorable stress distributions in implants/components and bone tissue. Splinting was favorable for stress distribution only for screwed prostheses under oblique loading.

Determination of a tissue-level failure evaluation standard for rat femoral cortical bone utilizing a hybrid computational-experimental method.

PubMed

Fan, Ruoxun; Liu, Jie; Jia, Zhengbin; Deng, Ying; Liu, Jun

2018-01-01

Macro-level failure in bone structure could be diagnosed by pain or physical examination. However, diagnosing tissue-level failure in a timely manner is challenging due to the difficulty in observing the interior mechanical environment of bone tissue. Because most fractures begin with tissue-level failure in bone tissue caused by continually applied loading, people attempt to monitor the tissue-level failure of bone and provide corresponding measures to prevent fracture. Many tissue-level mechanical parameters of bone could be predicted or measured; however, the value of the parameter may vary among different specimens belonging to a kind of bone structure even at the same age and anatomical site. These variations cause difficulty in representing tissue-level bone failure. Therefore, determining an appropriate tissue-level failure evaluation standard is necessary to represent tissue-level bone failure. In this study, the yield and failure processes of rat femoral cortical bones were primarily simulated through a hybrid computational-experimental method. Subsequently, the tissue-level strains and the ratio between tissue-level failure and yield strains in cortical bones were predicted. The results indicated that certain differences existed in tissue-level strains; however, slight variations in the ratio were observed among different cortical bones. Therefore, the ratio between tissue-level failure and yield strains for a kind of bone structure could be determined. This ratio may then be regarded as an appropriate tissue-level failure evaluation standard to represent the mechanical status of bone tissue.

Pathologic bone tissues in a Turkey vulture and a nonavian dinosaur: implications for interpreting endosteal bone and radial fibrolamellar bone in fossil dinosaurs.

PubMed

Chinsamy, Anusuya; Tumarkin-Deratzian, Allison

2009-09-01

We report on similar pathological bone microstructure in an extant turkey vulture (Cathartes aura) and a nonavian dinosaur from Transylvania. Both these individuals exhibit distinctive periosteal reactive bone deposition accompanied by endosteal bone deposits in the medullary cavity. Our findings have direct implications on the two novel bone tissues recently described among nonavian dinosaurs, radial fibrolamellar bone tissue and medullary bone tissue. On the basis of the observed morphology of the periosteal reactive bone in the turkey vulture and the Transylvanian dinosaur, we propose that the radial fibrolamellar bone tissues observed in mature dinosaurs may have had a pathological origin. Our analysis also shows that on the basis of origin, location, and morphology, pathologically derived endosteal bone tissue can be similar to medullary bone tissues described in nonavian dinosaurs. As such, we caution the interpretation of all endosteally derived bone tissue as homologous to avian medullary bone. (c) 2009 Wiley-Liss, Inc.

Comparing immunocompetent and immunodeficient mice as animal models for bone tissue engineering.

PubMed

Zhang, Y; Li, X; Chihara, T; Mizoguchi, T; Hori, A; Udagawa, N; Nakamura, H; Hasegawa, H; Taguchi, A; Shinohara, A; Kagami, H

2015-07-01

To understand the differences and similarities between immunocompetent and immunodeficient mice as ectopic transplantation animal models for bone tissue engineering. Osteogenic cells from mouse leg bones were cultured, seeded on β-TCP granules, and transplanted onto the backs of either immunocompetent or immunodeficient nude mice. At 1, 2, 4, and 8 weeks postoperatively, samples were harvested and evaluated by hematoxylin-eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemical staining and quantitative PCR. In immunocompetent mice, inflammatory cell infiltration was evident at 1 week postoperatively and relatively higher expression of TNF-α and IL-4 was observed. In immunodeficient mice, new bone area and the number of TRAP-positive cells were larger at 4 weeks than in immunocompetent mice. The volume of new bone area in immunodeficient mice was reduced by 8 weeks. Bone regeneration was feasible in immunocompetent mice. However, some differences were observed between immunocompetent and immunodeficient mice in the bone regeneration process possibly due to different cytokine expression, which should be considered when utilizing in vivo animal models. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Polymicrobial periodontal pathogens transcriptomes in calvarial bone and soft tissue

PubMed Central

Bakthavatchalu, Vasudevan; Meka, Archana; Mans, Jeffrey J.; Sathishkumar, Sabapathi; Lopez, M. Cecilia; Bhattacharyya, Indraneel; Boyce, Brendan F.; Baker, Henry V.; Lamont, Richard J.; Ebersole, Jeffrey L.; Kesavalu, L.

2011-01-01

Summary Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are consistently associated with adult periodontitis. This study sought to document the host transcriptome to a P. gingivalis, T. denticola, and T. forsythia challenge as a polymicrobial infection using a murine calvarial model of acute inflammation and bone resorption. Mice were infected with P. gingivalis, T. denticola, and T. forsythia over the calvaria, after which the soft tissues and calvarial bones were excised. A Murine GeneChip® array analysis of transcript profiles showed that 6997 genes were differentially expressed in calvarial bones (P < 0.05) and 1544 genes were differentially transcribed in the inflamed tissues after the polymicrobial infection. Of these genes, 4476 and 1035 genes in the infected bone and tissues were differentially expressed by upregulation. Biological pathways significantly impacted by the polymicrobial infection in calvarial bone included leukocyte transendothelial migration (LTM), cell adhesion molecules, adherens junction, major histocompatibility complex antigen, extracellular matrix-receptor interaction (ECM), and antigen processing and presentation resulting in inflammatory/cytokine/chemokine transcripts stimulation in bone and soft tissue. Intense inflammation and increased activated osteoclasts was observed in calvarias compared to sham-infected controls. Quantitative real-time RT-PCR analysis confirmed mRNA level of selected genes corresponded with the microarray expression. The polymicrobial infection regulated several LTM and extracellular membrane (ECM) pathway genes in a manner distinct from monoinfection with P. gingivalis, T. denticola, or T. forsythia. To our knowledge, this is the first definition of the polymicrobial induced transcriptome in calvarial bone and soft tissue in response to periodontal pathogens. PMID:21896157

Determination of in vivo mechanical properties of long bones from their impedance response curves

NASA Technical Reports Server (NTRS)

Borders, S. G.

1981-01-01

A mathematical model consisting of a uniform, linear, visco-elastic, Euler-Bernoulli beam to represent the ulna or tibia of the vibrating forearm or leg system is developed. The skin and tissue compressed between the probe and bone is represented by a spring in series with the beam. The remaining skin and tissue surrounding the bone is represented by a visco-elastic foundation with mass. An extensive parametric study is carried out to determine the effect of each parameter of the mathematical model on its impedance response. A system identification algorithm is developed and programmed on a digital computer to determine the parametric values of the model which best simulate the data obtained from an impedance test.

A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor κB Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis.

PubMed

Elburki, Muna S; Rossa, Carlos; Guimarães-Stabili, Morgana R; Lee, Hsi-Ming; Curylofo-Zotti, Fabiana A; Johnson, Francis; Golub, Lorne M

2017-08-01

The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-κB signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-κB) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-κB) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis.

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

PubMed

Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

2015-01-01

Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

Action Mechanism of Fibroblast Growth Factor-2 (FGF-2) in the Promotion of Periodontal Regeneration in Beagle Dogs

PubMed Central

Nagayasu-Tanaka, Toshie; Anzai, Jun; Takaki, Shu; Shiraishi, Noriko; Terashima, Akio; Asano, Taiji; Nozaki, Takenori; Kitamura, Masahiro; Murakami, Shinya

2015-01-01

Fibroblast growth factor-2 (FGF-2) enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL) in periodontal defect models. However, the mechanism through which FGF-2 acts in periodontal regeneration in vivo has not been fully clarified yet. To reveal the action mechanism, the formation of regenerated tissue and gene expression at the early phase were analyzed in a beagle dog 3-wall periodontal defect model. FGF-2 (0.3%) or the vehicle (hydroxypropyl cellulose) only were topically applied to the defect in FGF-2 and control groups, respectively. Then, the amount of regenerated tissues and the number of proliferating cells at 3, 7, 14, and 28 days and the number of blood vessels at 7 days were quantitated histologically. Additionally, the expression of osteogenic genes in the regenerated tissue was evaluated by real-time PCR at 7 and 14 days. Compared with the control, cell proliferation around the existing bone and PDL, connective tissue formation on the root surface, and new bone formation in the defect at 7 days were significantly promoted by FGF-2. Additionally, the number of blood vessels at 7 days was increased by FGF-2 treatment. At 28 days, new cementum and PDL were extended by FGF-2. Moreover, FGF-2 increased the expression of bone morphogenetic protein 2 (BMP-2) and osteoblast differentiation markers (osterix, alkaline phosphatase, and osteocalcin) in the regenerated tissue. We revealed the facilitatory mechanisms of FGF-2 in periodontal regeneration in vivo. First, the proliferation of fibroblastic cells derived from bone marrow and PDL was accelerated and enhanced by FGF-2. Second, angiogenesis was enhanced by FGF-2 treatment. Finally, osteoblastic differentiation and bone formation, at least in part due to BMP-2 production, were rapidly induced by FGF-2. Therefore, these multifaceted effects of FGF-2 promote new tissue formation at the early regeneration phase, leading to enhanced formation of new bone, cementum, and PDL. PMID:26120833

So You Want to Go to Mars: Bones and Matters of the Heart

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Globus, Ruth; Torres, Samantha; Steczina, Sonette

2017-01-01

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Collectively, our research team aims to understand the molecular mechanisms underlying the responses of mammalian tissue to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent tissue decrements induced by spaceflight and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will provide an overview of skeletal and cardiovascular responses to spaceflight and will highlight our research progress on understanding the role of reactive oxygen species (ROS) signaling in skeletal responses to radiation and simulated weightlessness.

Mandibular Repair in Rats with Premineralized Silk Scaffolds and BMP-2-modified bMSCs

PubMed Central

Jiang, Xinquan; Zhao, Jun; Wang, Shaoyi; Sun, Xiaojuan; Zhang, Xiuli; Chen, Jake; Kaplan, David L.; Zhang, Zhiyuan

2010-01-01

Premineralized silk fibroin protein scaffolds (mSS) were prepared to combine the osteoconductive properties of biological apatite with aqueous-derived silk scaffold (SS) as a composite scaffold for bone regeneration. The aim of present study was to evaluate the effect of premineralized silk scaffolds combined with bone morphogenetic protein-2 (BMP-2) modified bone marrow stromal cells (bMSCs) to repair mandibular bony defects in a rat model. bMSCs were expanded and transduced with adenovirus AdBMP-2, AdLacZ gene in vitro. These genetically modified bMSCs were then combined with premineralized silk scaffolds to form tissue engineered bone. Mandibular repairs with AdBMP-2 transduced bMSCs/mSS constructs were compared with those treated with AdLacZ transduced bMSCs/mSS constructs, native (nontransduced) bMSCs/mSS constructs and mSS alone. Eight weeks post-operation, the mandibles were explanted and evaluated by radiographic observation, micro-CT, histological analysis and immunohistochemistry. The presence of BMP-2 gene enhanced tissue engineered bone in terms of the most new bone formed and the highest local bone mineral densities (BMD) found. These results demonstrated that premineralized silk scaffold could serve as a potential substrate for bMSCs to construct tissue engineered bone for mandibular bony defects. BMP-2 gene therapy and tissue engineering techniques could be used in mandibular repair and bone regeneration. PMID:19501905

Characterization of focal muscle compression under impact loading

NASA Astrophysics Data System (ADS)

Butler, B. J.; Sory, D. R.; Nguyen, T.-T. N.; Proud, W. G.; Williams, A.; Brown, K. A.

2017-01-01

In modern wars over 70% of combat wounds are to the extremities. These injuries are characterized by disruption and contamination of the limb soft tissue envelope. The extent of this tissue trauma and contamination determine the outcome of the extremity injury. In military injury, common post-traumatic complications at amputation sites include heterotopic ossification (formation of bone in soft tissue), and severe soft tissue and bone infections. We are currently developing a model of soft tissue injury that recreates pathologies observed in combat injuries. Here we present characterization of a controlled focal compression of the rabbit flexor carpi ulnaris (FCU) muscle group. The FCU was previously identified as a suitable site for studying impact injury because its muscle belly can easily be mobilized from the underlying bone without disturbing anatomical alignment in the limb. We show how macroscopic changes in tissue organization, as visualized using optical microscopy, can be correlated with data from temporally resolved traces of loading conditions.

The osteoplastic effectiveness of the implants made of mesh titanium nickelide constructs

PubMed Central

Irianov, Iurii Mikhailovich; Diuriagina, Olga Vladimirovna; Karaseva, Tatiana Iurevna; Karasev, Evgenii Anatolevich

2014-01-01

The purpose of the work was to study the features of reparative osteogenesis for filling the defect of tubular bone under implantation of mesh titanium nickelide constructs. Tibial fenestrated defect was modeled experimentally in 30 Wistar pubertal rats, followed by implant intramedullary insertion. The techniques of radiography, scanning electron microscopy and X-ray electron probe microanalysis were used. The mesh implant of titanium nickelide has been established to possess biocompatibility, osteoconductive and osteoinductive properties, the zone of osteogenesis and angiogenesis is created around it, bone cover is formed. Osteointegration of the implant occurs early, by 7 days after surgery, and by 30 days after surgery organotypical re-modelling of the regenerated bone takes place, as well as the defect is filled with lamellar bone tissue by the type of bone wound primary adhesion. By 30 days after surgery mineral content of the regenerated bone tissue approximates to the composition of intact cortex mineral phase. PMID:24579962

An image-based skeletal dosimetry model for the ICRP reference adult male—internal electron sources

NASA Astrophysics Data System (ADS)

Hough, Matthew; Johnson, Perry; Rajon, Didier; Jokisch, Derek; Lee, Choonsik; Bolch, Wesley

2011-04-01

In this study, a comprehensive electron dosimetry model of the adult male skeletal tissues is presented. The model is constructed using the University of Florida adult male hybrid phantom of Lee et al (2010 Phys. Med. Biol. 55 339-63) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow, associated with radiogenic leukemia, and total shallow marrow, associated with radiogenic bone cancer. Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following sources: bone marrow (active and inactive), trabecular bone (surfaces and volumes), and cortical bone (surfaces and volumes). Specific absorbed fractions are computed according to the MIRD schema, and are given as skeletal-averaged values in the paper with site-specific values reported in both tabular and graphical format in an electronic annex available from http://stacks.iop.org/0031-9155/56/2309/mmedia. The distribution of cortical bone and spongiosa at the macroscopic dimensions of the phantom, as well as the distribution of trabecular bone and marrow tissues at the microscopic dimensions of the phantom, is imposed through detailed analyses of whole-body ex vivo CT images (1 mm resolution) and spongiosa-specific ex vivo microCT images (30 µm resolution), respectively, taken from a 40 year male cadaver. The method utilized in this work includes: (1) explicit accounting for changes in marrow self-dose with variations in marrow cellularity, (2) explicit accounting for electron escape from spongiosa, (3) explicit consideration of spongiosa cross-fire from cortical bone, and (4) explicit consideration of the ICRP's change in the surrogate tissue region defining the location of the osteoprogenitor cells (from a 10 µm endosteal layer covering the trabecular and cortical surfaces to a 50 µm shallow marrow layer covering trabecular and medullary cavity surfaces). Skeletal-averaged values of absorbed fraction in the present model are noted to be very compatible with those weighted by the skeletal tissue distributions found in the ICRP Publication 110 adult male and female voxel phantoms, but are in many cases incompatible with values used in current and widely implemented internal dosimetry software.

Nanocomposites for bone tissue regeneration.

PubMed

Sahoo, Nanda Gopal; Pan, Yong Zheng; Li, Lin; He, Chao Bin

2013-04-01

Natural bone tissue possesses a nanocomposite structure that provides appropriate physical and biological properties. For bone tissue regeneration, it is crucial for the biomaterial to mimic living bone tissue. Since no single type of material is able to mimic the composition, structure and properties of native bone, nanocomposites are the best choice for bone tissue regeneration as they can provide the appropriate matrix environment, integrate desirable biological properties, and provide controlled, sequential delivery of multiple growth factors for the different stages of bone tissue regeneration. This article reviews the composition, structure and properties of advanced nanocomposites for bone tissue regeneration. It covers aspects of interest such as the biomimetic synthesis of bone-like nanocomposites, guided bone regeneration from inert biomaterials and bioactive nanocomposites, and nanocomposite scaffolds for bone tissue regeneration. The design, fabrication, and in vitro and in vivo characterization of such nanocomposites are reviewed.

Biodegradation and biocompatability of a calcium sulphate-hydroxyapatite bone substitute.

PubMed

Nilsson, M; Wang, J S; Wielanek, L; Tanner, K E; Lidgren, L

2004-01-01

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth.

Regenerative Medicine for Periodontal and Peri-implant Diseases.

PubMed

Larsson, L; Decker, A M; Nibali, L; Pilipchuk, S P; Berglundh, T; Giannobile, W V

2016-03-01

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions. © International & American Associations for Dental Research 2015.

Electromechanical Properties of Bone Tissue.

NASA Astrophysics Data System (ADS)

Regimbal, Raymond L.

Discrepancies between calculated and empirical properties of bone are thought to be due to a general lack of consideration for the extent and manner(s) with which bone components interact at the molecular level. For a bone component in physiological fluid or whenever two phases are in contact, there is a region between the bulk phases called the electrical double layer which is marked by a separation of electric charges. For the purpose of studying electrical double layer interactions, the method of particle microelectrophoresis was used to characterize bone and its major constituents on the basis of the net charge they bear when suspended in ionic media of physiological relevance. With the data presented as pH versus zeta (zeta ) potential, the figures reveal an isoelectric point (IEP) for bone mineral near pH 8.6, whereas intact and EDTA demineralized bone tissue both exhibit IEPs near pH 5.1. While these data demonstrate the potential for a significant degree of coulombic interaction between the bone mineral and organic constituent double layers, it was also observed that use of inorganic phosphate buffers, as a specific marker for bone mineral, resulted in (1) an immediate reversal, from positive to negative, of the bone mineral zeta potential (2) rendered the zeta potential of intact bone more negative in a manner linearly dependent on both time and temperature and (3) had no affect on demineralized bone (P < 0.01). In agreement with that shown in model protein-hydroxyapatite systems, it is suggested here that inorganic phosphate ions in solution compete with organic acid groups (e.g. carboxyl and phosphate of collagen, sialoprotein, ...) for positively charged sites on the bone mineral surface and effectively uncouple the bone mineral and organic phase double layers. Mechanically, this uncoupling is manifested as a loss of tissue rigidity when monitoring the midspan deflection of bone beams subject to constant load for a 3 day period. While it is thus demonstrated that the major inorganic and organic phases of bone are electromechanically coupled, a thermodynamic consideration of the data suggests that the nature of the bond is to preserve mineral and organic phase electroneutralities by participating in electrical double layer interactions. The results are discussed in terms of bone mechanical modeling, electrokinetic properties, aging, tissue-implant compatibility and the etiologies of bone pathologic conditions.

Stem cell derived endochondral cartilage stimulates bone healing by tissue transformation

PubMed Central

Bahney, Chelsea S; Hu, Diane P; Taylor, Aaron J; Ferro, Federico; Britz, Hayley M; Hallgrimsson, Benedikt; Johnstone, Brian; Miclau, Theodore; Marcucio, Ralph S

2016-01-01

Although bone has great capacity for repair, there are a number of clinical situations (fracture non-unions, spinal fusions, revision arthroplasty, segmental defects) in which auto- or allografts augment bone regeneration. Critical failures associated with current grafting treatments include osteonecrosis and limited integration between graft and host tissue. We speculated that the underlying problem with current bone grafting techniques is that they promote bone regeneration through direct osteogenesis. We hypothesized that using cartilage to promote endochondral bone regeneration would leverage normal developmental and repair sequences to produce a well-vascularized regenerate that integrates with the host tissue. In this study we use a translational murine model of a segmental tibia defect to test the clinical utility of bone regeneration from a cartilage graft. We further test the mechanism by which cartilage promotes bone regeneration using in vivo lineage tracing and in vitro culture experiments. Our data show that cartilage grafts support regeneration of a vascularized and integrated bone tissue in vivo, and subsequently propose a translational tissue engineering platform using chondrogenesis of MSCs. Interestingly, lineage tracing experiments show the regenerate was graft derived, suggesting transformation of the chondrocytes into bone. In vitro culture data shows that cartilage explants mineralize with the addition of BMP or by exposure to HUVEC conditioned medium, indicating that endothelial cells directly promote ossification. This study provides pre-clinical data for endochondral bone repair that has potential to significantly improve patient outcomes in a variety of musculoskeletal diseases and injuries. Further, in contrast to the dogmatic view that hypertrophic chondrocytes undergo apoptosis prior to bone formation, our data suggest cartilage can transform into bone by activating the pluripotent transcription factor Oct4A. Together these data represent a paradigm shift describing the mechanism of endochondral bone repair and open the door for novel regenerative strategies based on improved biology. PMID:24259230

Mechanobiological simulations of peri-acetabular bone ingrowth: a comparative analysis of cell-phenotype specific and phenomenological algorithms.

PubMed

Mukherjee, Kaushik; Gupta, Sanjay

2017-03-01

Several mechanobiology algorithms have been employed to simulate bone ingrowth around porous coated implants. However, there is a scarcity of quantitative comparison between the efficacies of commonly used mechanoregulatory algorithms. The objectives of this study are: (1) to predict peri-acetabular bone ingrowth using cell-phenotype specific algorithm and to compare these predictions with those obtained using phenomenological algorithm and (2) to investigate the influences of cellular parameters on bone ingrowth. The variation in host bone material property and interfacial micromotion of the implanted pelvis were mapped onto the microscale model of implant-bone interface. An overall variation of 17-88 % in peri-acetabular bone ingrowth was observed. Despite differences in predicted tissue differentiation patterns during the initial period, both the algorithms predicted similar spatial distribution of neo-tissue layer, after attainment of equilibrium. Results indicated that phenomenological algorithm, being computationally faster than the cell-phenotype specific algorithm, might be used to predict peri-prosthetic bone ingrowth. The cell-phenotype specific algorithm, however, was found to be useful in numerically investigating the influence of alterations in cellular activities on bone ingrowth, owing to biologically related factors. Amongst the host of cellular activities, matrix production rate of bone tissue was found to have predominant influence on peri-acetabular bone ingrowth.

Effects of magnetic resonance-guided high-intensity focused ultrasound ablation on bone mechanical properties and modeling.

PubMed

Yeo, Sin Yuin; Arias Moreno, Andrés J; van Rietbergen, Bert; Ter Hoeve, Natalie D; van Diest, Paul J; Grüll, Holger

2015-01-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a promising technique for palliative treatment of bone pain. In this study, the effects of MR-HIFU ablation on bone mechanics and modeling were investigated. A total of 12 healthy rat femurs were ablated using 10 W for 46 ± 4 s per sonication with 4 sonications for each femur. At 7 days after treatments, all animals underwent MR and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Then, six animals were euthanized. At 1 month following ablations, the remaining six animals were scanned again with MR and SPECT/CT prior to euthanization. Thereafter, both the HIFU-treated and contralateral control bones of three animals from each time interval were processed for histology, whereas the remaining bones were subjected to micro-CT (μCT), three-point bending tests, and micro-finite element (micro-FE) analyses. At 7 days after HIFU ablations, edema formation around the treated bones coupled with bone marrow and cortical bone necrosis was observed on MRI and histological images. SPECT/CT and μCT images revealed presence of bone modeling through an increased uptake of (99m)Tc-MDP and formation of woven bone, respectively. At 31 days after ablations, as illustrated by imaging and histology, healing of the treated bone and the surrounding soft tissue was noted, marked by decreased in amount of tissue damage, formation of scar tissue, and sub-periosteal reaction. The results of three-point bending tests showed no significant differences in elastic stiffness, ultimate load, and yield load between the HIFU-treated and contralateral control bones at 7 days and 1 month after treatments. Similarly, the elastic stiffness and Young's moduli determined by micro-FE analyses at both time intervals were not statistically different. Multimodality imaging and histological data illustrated the presence of HIFU-induced bone damage at the cellular level, which activated the bone repair mechanisms. Despite that, these changes did not have a mechanical impact on the bone.

Bone engineering by phosphorylated-pullulan and β-TCP composite.

PubMed

Takahata, Tomohiro; Okihara, Takumi; Yoshida, Yasuhiro; Yoshihara, Kumiko; Shiozaki, Yasuyuki; Yoshida, Aki; Yamane, Kentaro; Watanabe, Noriyuki; Yoshimura, Masahide; Nakamura, Mariko; Irie, Masao; Van Meerbeek, Bart; Tanaka, Masato; Ozaki, Toshifumi; Matsukawa, Akihiro

2015-11-20

A multifunctional biomaterial with the capacity bond to hard tissues, such as bones and teeth, is a real need for medical and dental applications in tissue engineering and regenerative medicine. Recently, we created phosphorylated-pullulan (PPL), capable of binding to hydroxyapatite in bones and teeth. In the present study, we employed PPL as a novel biocompatible material for bone engineering. First, an in vitro evaluation of the mechanical properties of PPL demonstrated both PPL and PPL/β-TCP composites have higher shear bond strength than materials in current clinical use, including polymethylmethacrylate (PMMA) cement and α-tricalcium phosphate (TCP) cement, Biopex-R. Further, the compressive strength of PPL/β-TCP composite was significantly higher than Biopex-R. Next, in vivo osteoconductivity of PPL/β-TCP composite was investigated in a murine intramedular injection model. Bone formation was observed 5 weeks after injection of PPL/β-TCP composite, which was even more evident at 8 weeks; whereas, no bone formation was detected after injection of PPL alone. We then applied PPL/β-TCP composite to a rabbit ulnar bone defect model and observed bone formation comparable to that induced by Biopex-R. Implantation of PPL/β-TCP composite induced new bone formation at 4 weeks, which was remarkably evident at 8 weeks. In contrast, Biopex-R remained isolated from the surrounding bone at 8 weeks. In a pig vertebral bone defect model, defects treated with PPL/β-TCP composite were almost completely replaced by new bone; whereas, PPL alone failed to induce bone formation. Collectively, our results suggest PPL/β-TCP composite may be useful for bone engineering.

Stress Distribution in Splinted and Unsplinted Implant-Supported Maxillary Overdentures: A 3D Finite Element Analysis.

PubMed

Geramy, Allahyar; Habibzadeh, Sareh

2018-02-01

This study was accomplished to assess the biomechanical state of splinting in implant-supported maxillary overdentures. Two models of maxillary overdentures were designed in SolidWorks 2011. The first model included 4 separate implants and ball abutments, whereas the second one included 4 splinted implants connected with a bar. Evaluation was performed in ANSYS Workbench software with 200 N load applied at the molar-premolar region, bilaterally. The maximum equivalent stress and strain (von Mises) was recorded and analyzed along a path between the implants in the crestal bone and the prosthetic attachments. First model presented higher values of strain in prosthetic attachment and higher values of von Mises stress in crestal bone. The second model presented higher stress concentration in the gingival tissue of premolar area (near the bar), whereas the peak stress values were reported within the most distal part of the soft tissue support of the prosthesis in the first model (unsplinted). Splinting maxillary overdentures implants is associated with significant lower stress levels in the surrounding bone tissue.

Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems.

PubMed

Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin

2015-02-01

Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.

Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

PubMed

Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

2014-11-01

Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P < 0.05). Tissue-engineered bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

Biomechanics Analysis of Pressure Ulcer Using Damaged Interface Model between Bone and Muscle in the Human Buttock

NASA Astrophysics Data System (ADS)

Slamet, Samuel Susanto; Takano, Naoki; Tanabe, Yoshiyuki; Hatano, Asako; Nagasao, Tomohisa

This paper aims at building up a computational procedure to study the bio-mechanism of pressure ulcer using the finite element method. Pressure ulcer is a disease that occurs in the human body after 2 hours of continuous external force. In the very early stage of pressure ulcer, it is found that the tissues inside the body are damaged, even though skin surface looks normal. This study assumes that tension and/or shear strain will cause damage to loose fibril tissue between the bone and muscle and that propagation of damaged area will lead to fatal stage. Analysis was performed using the finite element method by modeling the damaged fibril tissue as a cutout. By varying the loading directions and watching both tensile and shear strains, the risk of fibril tissue damage and propagation of the damaged area is discussed, which may give new insight for the careful nursing for patients, particularly after surgical treatment. It was found that the pressure ulcer could reoccur for a surgical flap treatment. The bone cut and surgical flap surgery is not perfect to prevent the bone-muscle interfacial damage.

[Applicability of laser-based geological techniques in bone research: analysis of calcium oxide distribution in thin-cut animal bones].

PubMed

Andrássy, László; Maros, Gyula; Kovács, István János; Horváth, Ágnes; Gulyás, Katalin; Bertalan, Éva; Besnyi, Anikó; Füri, Judit; Fancsik, Tamás; Szekanecz, Zoltán; Bhattoa, Harjit Pal

2014-11-09

The structural similarities between the inorganic component of bone tissue and geological formations make it possible that mathematic models may be used to determine weight percentage composition of different mineral element oxides constituting the inorganic component of bone tissue. The determined weight percentage composition can be verified with the determination of element oxide concentration values by laser induced plasma spectroscopy and inductively coupled plasma optical emission spectrometry. It can be concluded from calculated weight percentage composition of the inorganic component of bone tissue and laboratory analyses that the properties of bone tissue are determined primarily by hydroxylapatite. The inorganic bone structure can be studied well by determining the calcium oxide concentration distribution using the laser induced plasma spectroscopy technique. In the present study, thin polished bone slides prepared from male bovine tibia were examined with laser induced plasma spectroscopy in a regular network and combined sampling system to derive the calculated calcium oxide concentration distribution. The superficial calcium oxide concentration distribution, as supported by "frequency distribution" curves, can be categorized into a number of groups. This, as such, helps in clearly demarcating the cortical and trabecular bone structures. Following analyses of bovine tibial bone, the authors found a positive association between the attenuation value, as determined by quantitative computer tomography and the "ρ" density, as used in geology. Furthermore, the calculated "ρ" density and the measured average calcium oxide concentration values showed inverse correlation.

The influence of different loads on the remodeling process of a bone and bioresorbable material mixture with voids

NASA Astrophysics Data System (ADS)

Giorgio, Ivan; Andreaus, Ugo; Madeo, Angela

2016-03-01

A model of a mixture of bone tissue and bioresorbable material with voids was used to numerically analyze the physiological balance between the processes of bone growth and resorption and artificial material resorption in a plate-like sample. The adopted model was derived from a theory for the behavior of porous solids in which the matrix material is linearly elastic and the interstices are void of material. The specimen—constituted by a region of bone living tissue and one of bioresorbable material—was acted by different in-plane loading conditions, namely pure bending and shear. Ranges of load magnitudes were identified within which physiological states become possible. Furthermore, the consequences of applying different loading conditions are examined at the end of the remodeling process. In particular, maximum value of bone and material mass densities, and extensions of the zones where bone is reconstructed were identified and compared in the two different load conditions. From the practical view point, during surgery planning and later rehabilitation, some choice of the following parameters is given: porosity of the graft, material characteristics of the graft, and adjustment of initial mixture tissue/bioresorbable material and later, during healing and remodeling, optimal loading conditions.

In silico multi-scale model of transport and dynamic seeding in a bone tissue engineering perfusion bioreactor.

PubMed

Spencer, T J; Hidalgo-Bastida, L A; Cartmell, S H; Halliday, I; Care, C M

2013-04-01

Computer simulations can potentially be used to design, predict, and inform properties for tissue engineering perfusion bioreactors. In this work, we investigate the flow properties that result from a particular poly-L-lactide porous scaffold and a particular choice of perfusion bioreactor vessel design used in bone tissue engineering. We also propose a model to investigate the dynamic seeding properties such as the homogeneity (or lack of) of the cellular distribution within the scaffold of the perfusion bioreactor: a pre-requisite for the subsequent successful uniform growth of a viable bone tissue engineered construct. Flows inside geometrically complex scaffolds have been investigated previously and results shown at these pore scales. Here, it is our aim to show accurately that through the use of modern high performance computers that the bioreactor device scale that encloses a scaffold can affect the flows and stresses within the pores throughout the scaffold which has implications for bioreactor design, control, and use. Central to this work is that the boundary conditions are derived from micro computed tomography scans of both a device chamber and scaffold in order to avoid generalizations and uncertainties. Dynamic seeding methods have also been shown to provide certain advantages over static seeding methods. We propose here a novel coupled model for dynamic seeding accounting for flow, species mass transport and cell advection-diffusion-attachment tuned for bone tissue engineering. The model highlights the timescale differences between different species suggesting that traditional homogeneous porous flow models of transport must be applied with caution to perfusion bioreactors. Our in silico data illustrate the extent to which these experiments have the potential to contribute to future design and development of large-scale bioreactors. Copyright © 2012 Wiley Periodicals, Inc.

In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration.

PubMed

Bicho, Diana; Pina, Sandra; Oliveira, J Miguel; Reis, Rui L

2018-01-01

In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.

Hierarchy effect on electronic structure and core-to-valence transitions in bone tissue: perspectives in medical nanodiagnostics of mineralized bone

NASA Astrophysics Data System (ADS)

Samoilenko, Dmitrii O.; Avrunin, Alexander S.; Pavlychev, Andrey A.

2017-06-01

Electronic structure and core-to-valence transitions in bone tissue are examined in the framework of the morphological 3DSL model that takes into account (i) structural and functional organization of the skeleton in the normal and pathological conditions and (ii) peculiarities of electron wave propagation in a three-dimensional superlattice of "black-nanocrystallites-in-muddy-waters". Our focus is on the HAP-to-bone red shifts of core-to-valence transitions near Ca and P 2p and O 1s edges in single-crystal hydroxyapatite (HAP) Ca10(PO4)6(OH)2. The origin of the HAP-to-bone shift is discussed and the extended comparative analysis of the experimental data is performed. The detected spectral shift is assigned with the effect of hierarchical organization of bone tissue. This hierarchy effect on the core-to-valence transition energies is regarded as a promising tool for medical imaging and perspective pathway for nanodiagnostics of mineralized bone. Contribution to the Topical Issue "Dynamics of Systems at the Nanoscale", edited by Andrey Solov'yov and Andrei Korol.

Investigation of angiogenesis in bioactive 3-dimensional poly(d,l-lactide-co-glycolide)/nano-hydroxyapatite scaffolds by in vivo multiphoton microscopy in murine calvarial critical bone defect.

PubMed

Li, Jian; Xu, Qiang; Teng, Bin; Yu, Chen; Li, Jian; Song, Liang; Lai, Yu-Xiao; Zhang, Jian; Zheng, Wei; Ren, Pei-Gen

2016-09-15

Reconstruction of critical size bone defects remains a major clinical challenge because of poor bone regeneration, which is usually due to poor angiogenesis during repair. Satisfactory vascularization is a prerequisite for the survival of grafts and the integration of new tissue with existing tissue. In this work, we investigated angiogenesis in 3D scaffolds by in vivo multiphoton microscopy during bone formation in a murine calvarial critical bone defect model and evaluated bone regeneration 8weeks post-implantation. The continuous release of bioactive lentiviral vectors (LV-pdgfb) from the scaffolds could be detected for 5days in vitro. In vivo, the released LV-pdgfb transfected adjacent cells and expressed PDGF-BB, facilitating angiogenesis and enhancing bone regeneration. The expression of both pdgfb and the angiogenesis-related genes vWF and VEGFR2 was significantly increased in the pdgfb gene-carrying scaffold (PHp) group. In addition, microCT scanning and histomorphology results proved that there was more new bone ingrowth in the PHp group than in the PLGA/nHA (PH) and control groups. MicroCT parameters, including BMD, BV/TV, Tb.Sp, and Tb.N indicated that there was significantly more new bone formation in the PHp group than in the other groups. With regard to neovascularization, 8weeks post-implantation, blood vessel areas (BVAs) were 9428±944μm(2), 4090±680.3μm(2), and none in the PHp, PH, and control groups, respectively. At each time point, BVAs in the PHp scaffolds were significantly higher than in the PH scaffolds. To our knowledge, this is the first use of multiphoton microscopy in bone tissue-engineering to investigate angiogenesis in scaffolds in vivo. This method represents a valuable tool for investigating neovascularization in bone scaffolds to determine if a certain scaffold is beneficial to neovascularization. We also proved that delivery of the pdgfb gene alone can improve both angiogenesis and bone regeneration Acronyms. Reconstruction of critical size bone defects remains a major clinical challenge because of poor bone regeneration, which is usually due to poor angiogenesis during repair. Satisfactory vascularization is a prerequisite for the survival of grafts and the integration of new tissue with existing tissue. In this work, we investigated angiogenesis in 3D scaffolds by in vivo multiphoton microscopy during bone formation in a murine calvarial critical bone defect model and evaluated bone regeneration 8weeks post-implantation. To verify that pdgfb-expressing vectors carried by the scaffolds can promote angiogenesis in 3D-printed scaffolds in vivo, we monitored angiogenesis within the implants by multiphoton microscopy. To our knowledge, this is the first study to dynamically investigate angiogenesis in bone tissue engineering scaffolds in vivo. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Stress distribution in fixed-partial prosthesis and peri-implant bone tissue with different framework materials and vertical misfit levels: a three-dimensional finite element analysis.

PubMed

Bacchi, Ataís; Consani, Rafael L X; Mesquita, Marcelo F; dos Santos, Mateus B F

2013-09-01

The purpose of this study was to evaluate the influence of superstructure material and vertical misfits on the stresses created in an implant-supported partial prosthesis. A three-dimensional (3-D) finite element model was prepared based on common clinical data. The posterior part of a severely resorbed jaw with two osseointegrated implants at the second premolar and second molar regions was modeled using specific modeling software (SolidWorks 2010). Finite element models were created by importing the solid model into mechanical simulation software (ANSYS Workbench 11). The models were divided into groups according to the prosthesis framework material (type IV gold alloy, silver-palladium alloy, commercially pure titanium, cobalt-chromium alloy, or zirconia) and vertical misfit level (10 µm, 50 µm, and 100 µm) created at one implant-prosthesis interface. The gap of the vertical misfit was set to be closed and the stress values were measured in the framework, porcelain veneer, retention screw, and bone tissue. Stiffer materials led to higher stress concentration in the framework and increased stress values in the retention screw, while in the same circumstances, the porcelain veneer showed lower stress values, and there was no significant difference in stress in the peri-implant bone tissue. A considerable increase in stress concentration was observed in all the structures evaluated within the misfit amplification. The framework material influenced the stress concentration in the prosthetic structures and retention screw, but not that in bone tissue. All the structures were significantly influenced by the increase in the misfit levels.

Evaluation of implant osseointegration with different regeneration techniques in the treatment of bone defects around implants: an experimental study in a rabbit model.

PubMed

Guerra, Isabel; Morais Branco, Fernando; Vasconcelos, Mário; Afonso, Américo; Figueiral, Helena; Zita, Raquel

2011-03-01

The aim of this study was to evaluate the osseointegration of implants placed in areas with artificially created bone defects, using three bone regeneration techniques. The experimental model was the rabbit femur (16), where bone defects were created and implants were placed. The peri-implant bone defects were filled with a deproteinized bovine bone mineral, NuOss™ (N), NuOss™ combined with plasma rich in growth factors (PRGF) (N+PRGF), NuOss™ covered by an RCM(6) membrane (N+M), or remained unfilled (control group [C]). After 4 and 8 weeks, the animals were euthanized and bone tissue blocks with the implants and the surrounding bone tissue were removed and processed according to a histological protocol for hard tissues on non-decalcified ground sections. The samples were studied by light and electron scanning microscopy, histometric analysis was performed to assess the percentage of bone in direct contact with the implant surface and a statistical analysis of the results was performed. In the samples analyzed 4 weeks after implantation, the percentage of bone tissue in direct contact with the implant surface for the four groups were 57.66±24.39% (N), 58.62±20.37% (N+PRGF), 70.82±20.34 % (N+M) and 33.07±5.49% (C). In the samples with 8 weeks of implantation time, the percentage of bone in direct contact was 63.35±27.69% (N), 58.42±24.77% (N+PRGF), 78.02±15.13% (N+M) and 40.28±27.32% (C). In terms of the percentage of bone contact, groups N and N+M presented statistically significant differences from group C in the 4-week trial test (P<0.05; ANOVA). For the 8-week results, only group N+M showed statistically significant differences when compared with group C (P<0.05; ANOVA). In conclusion, the NuOss™ granules/RCM(6) membrane combination presented a percentage of bone contact with the implant surface statistically greater than in the other groups. © 2010 John Wiley & Sons A/S.

Microgravity

NASA Image and Video Library

2000-12-15

Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Even in normal gravity, bioactive glass particles enhance bone growth in laboratory tests with flat tissue cultures. Ducheyne and his team believe that using the bioactive microcarriers in a rotating bioreactor in microgravity will produce improved, three-dimensional tissue cultures. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: NASA and University of Pennsylvania Center for Bioactive Materials and Tissue Engineering.

Bionic Design, Materials and Performance of Bone Tissue Scaffolds

PubMed Central

Wu, Tong; Yu, Suihuai; Chen, Dengkai; Wang, Yanen

2017-01-01

Design, materials, and performance are important factors in the research of bone tissue scaffolds. This work briefly describes the bone scaffolds and their anatomic structure, as well as their biological and mechanical characteristics. Furthermore, we reviewed the characteristics of metal materials, inorganic materials, organic polymer materials, and composite materials. The importance of the bionic design in preoperative diagnosis models and customized bone scaffolds was also discussed, addressing both the bionic structure design (macro and micro structure) and the bionic performance design (mechanical performance and biological performance). Materials and performance are the two main problems in the development of customized bone scaffolds. Bionic design is an effective way to solve these problems, which could improve the clinical application of bone scaffolds, by creating a balance between mechanical performance and biological performance. PMID:29039749

Bionic Design, Materials and Performance of Bone Tissue Scaffolds.

PubMed

Wu, Tong; Yu, Suihuai; Chen, Dengkai; Wang, Yanen

2017-10-17

Design, materials, and performance are important factors in the research of bone tissue scaffolds. This work briefly describes the bone scaffolds and their anatomic structure, as well as their biological and mechanical characteristics. Furthermore, we reviewed the characteristics of metal materials, inorganic materials, organic polymer materials, and composite materials. The importance of the bionic design in preoperative diagnosis models and customized bone scaffolds was also discussed, addressing both the bionic structure design (macro and micro structure) and the bionic performance design (mechanical performance and biological performance). Materials and performance are the two main problems in the development of customized bone scaffolds. Bionic design is an effective way to solve these problems, which could improve the clinical application of bone scaffolds, by creating a balance between mechanical performance and biological performance.

Advances in bionanomaterials for bone tissue engineering.

PubMed

Scott, Timothy G; Blackburn, Gary; Ashley, Michael; Bayer, Ilker S; Ghosh, Anindya; Biris, Alexandru S; Biswas, Abhijit

2013-01-01

Bone is a specialized form of connective tissue that forms the skeleton of the body and is built at the nano and microscale levels as a multi-component composite material consisting of a hard inorganic phase (minerals) in an elastic, dense organic network. Mimicking bone structure and its properties present an important frontier in the fields of nanotechnology, materials science and bone tissue engineering, given the complex morphology of this tissue. There has been a growing interest in developing artificial bone-mimetic nanomaterials with controllable mineral content, nanostructure, chemistry for bone, cartilage tissue engineering and substitutes. This review describes recent advances in bionanomaterials for bone tissue engineering including developments in soft tissue engineering. The significance and basic process of bone tissue engineering along with different bionanomaterial bone scaffolds made of nanocomposites and nanostructured biopolymers/bioceramics and the prerequisite biomechanical functions are described. It also covers latest developments in soft-tissue reconstruction and replacement. Finally, perspectives on the future direction in nanotechnology-enabled bone tissue engineering are presented.

Promise of periodontal ligament stem cells in regeneration of periodontium.

PubMed

Maeda, Hidefumi; Tomokiyo, Atsushi; Fujii, Shinsuke; Wada, Naohisa; Akamine, Akifumi

2011-07-28

A great number of patients around the world experience tooth loss that is attributed to irretrievable damage of the periodontium caused by deep caries, severe periodontal diseases or irreversible trauma. The periodontium is a complex tissue composed mainly of two soft tissues and two hard tissues; the former includes the periodontal ligament (PDL) tissue and gingival tissue, and the latter includes alveolar bone and cementum covering the tooth root. Tissue engineering techniques are therefore required for regeneration of these tissues. In particular, PDL is a dynamic connective tissue that is subjected to continual adaptation to maintain tissue size and width, as well as structural integrity, including ligament fibers and bone modeling. PDL tissue is central in the periodontium to retain the tooth in the bone socket, and is currently recognized to include somatic mesenchymal stem cells that could reconstruct the periodontium. However, successful treatment using these stem cells to regenerate the periodontium efficiently has not yet been developed. In the present article, we discuss the contemporary standpoints and approaches for these stem cells in the field of regenerative medicine in dentistry.

Influence of functionally graded pores on bone ingrowth in cementless hip prosthesis: a finite element study using mechano-regulatory algorithm.

PubMed

Tarlochan, Faris; Mehboob, Hassan; Mehboob, Ali; Chang, Seung-Hwan

2018-06-01

Cementless hip prostheses with porous outer coating are commonly used to repair the proximally damaged femurs. It has been demonstrated that stability of prosthesis is also highly dependent on the bone ingrowth into the porous texture. Bone ingrowth is influenced by the mechanical environment produced in the callus. In this study, bone ingrowth into the porous structure was predicted by using a mechano-regulatory model. Homogenously distributed pores (200 and 800 [Formula: see text]m in diameter) and functionally graded pores along the length of the prosthesis were introduced as a porous coating. Bone ingrowth was simulated using 25 and 12 [Formula: see text]m micromovements. Load control simulations were carried out instead of traditionally used displacement control. Spatial and temporal distributions of tissues were predicted in all cases. Functionally graded pore decreasing models gave the most homogenous bone distribution, the highest bone ingrowth (98%) with highest average Young's modulus of all tissue phenotypes approximately 4.1 GPa. Besides this, the volume of the initial callus increased to 8.33% in functionally graded pores as compared to the 200 [Formula: see text]m pore size models which increased the bone volume. These findings indicate that functionally graded porous surface promote bone ingrowth efficiently which can be considered to design of surface texture of hip prosthesis.

Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.

PubMed

Beattie, James; Al-Khafaji, Hasanain; Noer, Pernille R; Alkharobi, Hanaa Esa; Alhodhodi, Aishah; Meade, Josephine; El-Gendy, Reem; Oxvig, Claus

2018-01-01

The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.

Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

PubMed

Chevalier, Yan; Santos, Inês; Müller, Peter E; Pietschmann, Matthias F

2016-06-14

Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Female pelvic synthetic CT generation based on joint intensity and shape analysis

NASA Astrophysics Data System (ADS)

Liu, Lianli; Jolly, Shruti; Cao, Yue; Vineberg, Karen; Fessler, Jeffrey A.; Balter, James M.

2017-04-01

Using MRI for radiotherapy treatment planning and image guidance is appealing as it provides superior soft tissue information over CT scans and avoids possible systematic errors introduced by aligning MR to CT images. This study presents a method that generates Synthetic CT (MRCT) volumes by performing probabilistic tissue classification of voxels from MRI data using a single imaging sequence (T1 Dixon). The intensity overlap between different tissues on MR images, a major challenge for voxel-based MRCT generation methods, is addressed by adding bone shape information to an intensity-based classification scheme. A simple pelvic bone shape model, built from principal component analysis of pelvis shape from 30 CT image volumes, is fitted to the MR volumes. The shape model generates a rough bone mask that excludes air and covers bone along with some surrounding soft tissues. Air regions are identified and masked out from the tissue classification process by intensity thresholding outside the bone mask. A regularization term is added to the fuzzy c-means classification scheme that constrains voxels outside the bone mask from being assigned memberships in the bone class. MRCT image volumes are generated by multiplying the probability of each voxel being represented in each class with assigned attenuation values of the corresponding class and summing the result across all classes. The MRCT images presented intensity distributions similar to CT images with a mean absolute error of 13.7 HU for muscle, 15.9 HU for fat, 49.1 HU for intra-pelvic soft tissues, 129.1 HU for marrow and 274.4 HU for bony tissues across 9 patients. Volumetric modulated arc therapy (VMAT) plans were optimized using MRCT-derived electron densities, and doses were recalculated using corresponding CT-derived density grids. Dose differences to planning target volumes were small with mean/standard deviation of 0.21/0.42 Gy for D0.5cc and 0.29/0.33 Gy for D99%. The results demonstrate the accuracy of the method and its potential in supporting MRI only radiotherapy treatment planning.

Periodontal Tissues, Maxillary Jaw Bone, and Tooth Regeneration Approaches: From Animal Models Analyses to Clinical Applications

PubMed Central

Batool, Fareeha; Strub, Marion; Petit, Catherine; Bugueno, Isaac Maximiliano; Bornert, Fabien; Clauss, François; Kuchler-Bopp, Sabine; Benkirane-Jessel, Nadia

2018-01-01

This review encompasses different pre-clinical bioengineering approaches for periodontal tissues, maxillary jaw bone, and the entire tooth. Moreover, it sheds light on their potential clinical therapeutic applications in the field of regenerative medicine. Herein, the electrospinning method for the synthesis of polycaprolactone (PCL) membranes, that are capable of mimicking the extracellular matrix (ECM), has been described. Furthermore, their functionalization with cyclosporine A (CsA), bone morphogenetic protein-2 (BMP-2), or anti-inflammatory drugs’ nanoreservoirs has been demonstrated to induce a localized and targeted action of these molecules after implantation in the maxillary jaw bone. Firstly, periodontal wound healing has been studied in an induced periodontal lesion in mice using an ibuprofen-functionalized PCL membrane. Thereafter, the kinetics of maxillary bone regeneration in a pre-clinical mouse model of surgical bone lesion treated with BMP-2 or BMP-2/Ibuprofen functionalized PCL membranes have been analyzed by histology, immunology, and micro-computed tomography (micro-CT). Furthermore, the achievement of innervation in bioengineered teeth has also been demonstrated after the co-implantation of cultured dental cell reassociations with a trigeminal ganglia (TG) and the cyclosporine A (CsA)-loaded poly(lactic-co-glycolic acid) (PLGA) scaffold in the jaw bone. The prospective clinical applications of these different tissue engineering approaches could be instrumental in the treatment of various periodontal diseases, congenital dental or cranio-facial bone anomalies, and post-surgical complications. PMID:29772691

Accessibility of ³H-secoisolariciresinol diglycoside lignan metabolites in skeletal tissue of ovariectomized rats.

PubMed

Sacco, Sandra M; Thompson, Lilian U; Ganss, Bernhard; Ward, Wendy E

2011-10-01

Flaxseed, rich in the phytoestrogen lignan secoisolariciresinol diglycoside (SDG), provides protection against bone loss at the lumbar vertebrae primarily when combined with low-dose estrogen therapy in the ovariectomized rat model of postmenopausal osteoporosis. Whether SDG metabolites are accessible to skeletal tissue, and thus have the potential to interact with low-dose estrogen therapy to exert direct local action on bone metabolism, is unknown. The objective of this study was to determine whether metabolites of SDG are accessible to the skeleton of ovariectomized rats and to compare the distribution of SDG metabolites in skeletal tissue with that in other tissues. Rats were fed a 10% flaxseed diet and gavaged daily with tritium-labeled SDG (7.4 kBq/g of body weight) in deionized water (500 μL) (n=3) or deionized water alone (n=3) for 7 days, after which tissues were collected for liquid scintillation counting. Radioactivity was detected in similar concentrations in the lumbar vertebrae, femurs, and tibias. Compared with non-skeletal tissues, total radioactivity in the skeleton was significantly lower than in the liver, heart, kidney, thymus, and brain (P < .001). There were no significant differences in levels of radioactivity between skeletal tissue versus the spleen, lung, bladder, uterus, vagina, and mammary gland. In conclusion, SDG metabolites are accessible to skeletal tissue of ovariectomized rats. Thus, it is biologically plausible that SDG metabolites may play a direct role in the protective effects of flaxseed combined with low-dose estrogen therapy against the loss of bone mass and bone strength in the ovariectomized rat model of postmenopausal osteoporosis.

The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities

PubMed Central

Chen, Xiaoping; Song, Fengyu; Jhamb, Deepali; Li, Jiliang; Bottino, Marco C.; Palakal, Mathew J.; Stocum, David L.

2015-01-01

We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process. PMID:26098852

The poro-viscoelastic properties of trabecular bone: a micro computed tomography-based finite element study.

PubMed

Sandino, Clara; McErlain, David D; Schipilow, John; Boyd, Steven K

2015-04-01

Bone is a porous structure with a solid phase that contains hydroxyapatite and collagen. Due to its composition, bone is often represented either as a poroelastic or as a viscoelastic material; however, the poro-viscoelastic formulation that allows integrating the effect of both the fluid flow and the collagen on the mechanical response of the tissue, has not been applied yet. The objective of this study was to develop a micro computed tomography (µCT)-based finite element (FE) model of trabecular bone that includes both the poroelastic and the viscoelastic nature of the tissue. Cubes of trabecular bone (N=25) from human distal tibia were scanned with µCT and stress relaxation experiments were conducted. The µCT images were the basis for sample specific FE models, and the stress relaxation experiments were simulated applying a poro-viscoelastic formulation. The model considers two scales of the tissue: the intertrabecular pore and the lacunar-canalicular pore scales. Independent viscoelastic and poroelastic models were also developed to determine their contribution to the poro-viscoelastic model. All the experiments exhibited a similar relaxation trend. The average reaction force before relaxation was 9.28 × 10(2)N (SD ± 5.11 × 10(2)N), and after relaxation was 4.69 × 10(2)N (SD ± 2.88 × 10(2)N). The slope of the regression line between the force before and after relaxation was 1.92 (R(2)=0.96). The poro-viscoelastic models captured 49% of the variability of the experimental data before relaxation and 33% after relaxation. The relaxation predicted with viscoelastic models was similar to the poro-viscoelastic ones; however, the poroelastic formulation underestimated the reaction force before relaxation. These data suggest that the contribution of viscoelasticity (fluid flow-independent mechanism) to the mechanical response of the tissue is significantly greater than the contribution of the poroelasticity (fluid flow-dependent mechanism). Copyright © 2015 Elsevier Ltd. All rights reserved.

Implementing Capsule Representation in a Total Hip Dislocation Finite Element Model

PubMed Central

Stewart, Kristofer J; Pedersen, Douglas R; Callaghan, John J; Brown, Thomas D

2004-01-01

Previously validated hardware-only finite element models of THA dislocation have clarified how various component design and surgical placement variables contribute to resisting the propensity for implant dislocation. This body of work has now been enhanced with the incorporation of experimentally based capsule representation, and with anatomic bone structures. The current form of this finite element model provides for large deformation multi-body contact (including capsule wrap-around on bone and/or implant), large displacement interfacial sliding, and large deformation (hyperelastic) capsule representation. In addition, the modular nature of this model now allows for rapid incorporation of current or future total hip implant designs, accepts complex multi-axial physiologic motion inputs, and outputs case-specific component/bone/soft-tissue impingement events. This soft-tissue-augmented finite element model is being used to investigate the performance of various implant designs for a range of clinically-representative soft tissue integrities and surgical techniques. Preliminary results show that capsule enhancement makes a substantial difference in stability, compared to an otherwise identical hardware-only model. This model is intended to help put implant design and surgical technique decisions on a firmer scientific basis, in terms of reducing the likelihood of dislocation. PMID:15296198

Multiscale mechanobiology of de novo bone generation, remodeling and adaptation of autograft in a common ovine femur model.

PubMed

Knothe Tate, Melissa L; Dolejs, Scott; McBride, Sarah H; Matthew Miller, R; Knothe, Ulf R

2011-08-01

The link between mechanics and biology in the generation and the adaptation of bone has been studied for more than a century in the context of skeletal development and fracture healing. However, the interplay between mechanics and biology in de novo generation of bone in postnatal defects as well as healing of morcellized bone graft or massive cortical bone autografts is less well understood. To address this, here we integrate insights from our previously published studies describing the mechanobiology on both de novo bone generation and graft healing in a common ovine femoral defect model. Studying these effects in a common experimental model provides a unique opportunity to elucidate factors conducive to harnessing the regenerative power of the periosteum, and ultimately, to provide mechanistic insights into the multiscale mechanobiology of bone generation, remodeling and adaptation. Taken together, the studies indicate that, as long as adequate, directional transport of cells and molecules can be insured (e.g. with periosteum in situ or a delivery device), biological factors intrinsic to the periosteum suffice to bridge critical sized bone defects, even in the absence of a patent blood supply. Furthermore, mechanical stimuli are crucial for the success of periosteal bone generation and bone graft healing. Interestingly, areas of highest periosteal strain around defects correlate with greatest amounts albeit not greatest mineralization of newly generated bone. This may indicate a role for convection enhanced transport of cells and molecules in modulation of tissue generation by pluripotent cells that ingress into the defect center, away from the periosteum and toward the surface of the intramedullary nail that fills the medullary cavity. These insights bring us much closer to understanding the mechanobiological environment and stimuli that stimulate the proliferation and differentiation of periosteum-derived progenitor cells and ultimately drive the generation of new bone tissue. Furthermore, these insights provide a foundation to create virtual predictive computational models of bone mechanophysiology, to develop cell seeding protocols for scale up and manufacture of engineered tissues, to optimize surgical procedures, and to develop post-surgical therapies with the ultimate goal of achieving the best possible healing outcomes for treatment and/or reconstruction of postnatal bone defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Continuous versus short-term infusion of cefuroxime: assessment of concept based on plasma, subcutaneous tissue, and bone pharmacokinetics in an animal model.

PubMed

Tøttrup, Mikkel; Bibby, Bo M; Hardlei, Tore F; Bue, Mats; Kerrn-Jespersen, Sigrid; Fuursted, Kurt; Søballe, Kjeld; Birke-Sørensen, Hanne

2015-01-01

The relatively short half-lives of most β-lactams suggest that continuous infusion of these time-dependent antimicrobials may be favorable compared to short-term infusion. Nevertheless, only limited solid-tissue pharmacokinetic data are available to support this theory. In this study, we randomly assigned 12 pigs to receive cefuroxime as either a short-term or continuous infusion. Measurements of cefuroxime were obtained every 30 min in plasma, subcutaneous tissue, and bone. For the measurements in solid tissues, microdialysis was applied. A two-compartment population model was fitted separately to the drug concentration data for the different tissues using a nonlinear mixed-effects regression model. Estimates of the pharmacokinetic parameters and time with concentrations above the MIC were derived using Monte Carlo simulations. Except for subcutaneous tissue in the short-term infusion group, the tissue penetration was incomplete for all tissues. For short-term infusion, the tissue penetration ratios were 0.97 (95% confidence interval [CI], 0.67 to 1.39), 0.61 (95% CI, 0.51 to 0.73), and 0.45 (95% CI, 0.36 to 0.56) for subcutaneous tissue, cancellous bone, and cortical bone, respectively. For continuous infusion, they were 0.53 (95% CI, 0.33 to 0.84), 0.38 (95% CI, 0.23 to 0.57), and 0.27 (95% CI, 0.13 to 0.48) for the same tissues, respectively. The absolute areas under the concentration-time curve were also lower in the continuous infusion group. Nevertheless, a significantly longer time with concentrations above the MIC was found for continuous infusion up until MICs of 4, 2, 2, and 0.5 μg/ml for plasma and the same three tissues mentioned above, respectively. For drugs with a short half-life, like cefuroxime, continuous infusion seems to be favorable compared to short-term infusion; however, incomplete tissue penetration and high MIC strains may jeopardize the continuous infusion approach. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Assessment of Cortical and Trabecular Bone Changes in Two Models of Post-Traumatic Osteoarthritis

PubMed Central

Pauly, Hannah M; Larson, Blair E; Coatney, Garrett A; Button, Keith D.; DeCamp, Charlie E; Fajardo, Ryan S; Haut, Roger C; Donahue, Tammy L Haut

2015-01-01

Subchondral bone is thought to play a significant role in the initiation and progression of the post-traumatic osteoarthritis. The goal of this study was to document changes in tibial and femoral subchondral bone that occur as a result of two lapine models of anterior cruciate ligament injury, a modified ACL transection model and a closed-joint traumatic compressive impact model. Twelve weeks post-injury bones were scanned via micro-computed tomography. The subchondral bone of injured limbs from both models showed decreases in bone volume and bone mineral density. Surgical transection animals showed significant bone changes primarily in the medial hemijoint of femurs and tibias, while significant changes were noted in both the medial and lateral hemijoints of both bones for traumatic impact animals. It is believed that subchondral bone changes in the medial hemijoint were likely caused by compromised soft tissue structures seen in both models. Subchondral bone changes in the lateral hemijoint of traumatic impact animals are thought to be due to transmission of the compressive impact force through the joint. The joint-wide bone changes shown in the traumatic impact model were similar to clinical findings from studies investigating the progression of osteoarthritis in humans. PMID:26147652

Technical Note: Radiological properties of tissue surrogates used in a multimodality deformable pelvic phantom for MR-guided radiotherapy

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

Niebuhr, Nina I., E-mail: n.niebuhr@dkfz.de; Johnen, Wibke; Güldaglar, Timur

Purpose: Phantom surrogates were developed to allow multimodal [computed tomography (CT), magnetic resonance imaging (MRI), and teletherapy] and anthropomorphic tissue simulation as well as materials and methods to construct deformable organ shapes and anthropomorphic bone models. Methods: Agarose gels of variable concentrations and loadings were investigated to simulate various soft tissue types. Oils, fats, and Vaseline were investigated as surrogates for adipose tissue and bone marrow. Anthropomorphic shapes of bone and organs were realized using 3D-printing techniques based on segmentations of patient CT-scans. All materials were characterized in dual energy CT and MRI to adapt CT numbers, electron density, effectivemore » atomic number, as well as T1- and T2-relaxation times to patient and literature values. Results: Soft tissue simulation could be achieved with agarose gels in combination with a gadolinium-based contrast agent and NaF to simulate muscle, prostate, and tumor tissues. Vegetable oils were shown to be a good representation for adipose tissue in all modalities. Inner bone was realized using a mixture of Vaseline and K{sub 2}HPO{sub 4}, resulting in both a fatty bone marrow signal in MRI and inhomogeneous areas of low and high attenuation in CT. The high attenuation of outer bone was additionally adapted by applying gypsum bandages to the 3D-printed hollow bone case with values up to 1200 HU. Deformable hollow organs were manufactured using silicone. Signal loss in the MR images based on the conductivity of the gels needs to be further investigated. Conclusions: The presented surrogates and techniques allow the customized construction of multimodality, anthropomorphic, and deformable phantoms as exemplarily shown for a pelvic phantom, which is intended to study adaptive treatment scenarios in MR-guided radiation therapy.« less

Technical Note: Radiological properties of tissue surrogates used in a multimodality deformable pelvic phantom for MR-guided radiotherapy.

PubMed

Niebuhr, Nina I; Johnen, Wibke; Güldaglar, Timur; Runz, Armin; Echner, Gernot; Mann, Philipp; Möhler, Christian; Pfaffenberger, Asja; Jäkel, Oliver; Greilich, Steffen

2016-02-01

Phantom surrogates were developed to allow multimodal [computed tomography (CT), magnetic resonance imaging (MRI), and teletherapy] and anthropomorphic tissue simulation as well as materials and methods to construct deformable organ shapes and anthropomorphic bone models. Agarose gels of variable concentrations and loadings were investigated to simulate various soft tissue types. Oils, fats, and Vaseline were investigated as surrogates for adipose tissue and bone marrow. Anthropomorphic shapes of bone and organs were realized using 3D-printing techniques based on segmentations of patient CT-scans. All materials were characterized in dual energy CT and MRI to adapt CT numbers, electron density, effective atomic number, as well as T1- and T2-relaxation times to patient and literature values. Soft tissue simulation could be achieved with agarose gels in combination with a gadolinium-based contrast agent and NaF to simulate muscle, prostate, and tumor tissues. Vegetable oils were shown to be a good representation for adipose tissue in all modalities. Inner bone was realized using a mixture of Vaseline and K2HPO4, resulting in both a fatty bone marrow signal in MRI and inhomogeneous areas of low and high attenuation in CT. The high attenuation of outer bone was additionally adapted by applying gypsum bandages to the 3D-printed hollow bone case with values up to 1200 HU. Deformable hollow organs were manufactured using silicone. Signal loss in the MR images based on the conductivity of the gels needs to be further investigated. The presented surrogates and techniques allow the customized construction of multimodality, anthropomorphic, and deformable phantoms as exemplarily shown for a pelvic phantom, which is intended to study adaptive treatment scenarios in MR-guided radiation therapy.

Analysis of load distribution in tooth-implant supported fixed partial dentures by the use of resilient abutment.

PubMed

Glisić, Mirko; Stamenković, Dragoslav; Grbović, Aleksandar; Todorović, Aleksandar; Marković, Aleksa; Trifković, Branka

2016-01-01

Differences between the tooth and implant response to load can lead to many biological and technical implications in the conditions of occlusal forces. The objective of this study was to analyze load distribution in tooth/implant-supported fixed partial dentures with the use of resilient TSA (Titan Shock Absorber, BoneCare GmbH, Augsburg, Germany) abutment and conventional non-resilient abutment using finite element method. This study presents two basic 3D models. For one model a standard non-resilient abutment is used, and on the implant of the second model a resilient TSA abutment is applied. The virtual model contains drawn contours of tooth, mucous membranes, implant, cortical bones and spongiosa, abutment and suprastructure. The experiment used 500 N of vertical force, applied in three different cases of axial load. Calculations of von Mises equivalent stresses of the tooth root and periodontium, implants and peri-implant tissue were made. For the model to which a non-resilient abutment is applied, maximum stress values in all three cases are observed in the cortical part of the bone (maximum stress value of 49.7 MPa). Measurements of stress and deformation in the bone tissue in the model with application of the resilientTSA abutment demonstrated similar distribution; however, these values are many times lower than in the model with non-resilient TSA abutment (maximum stress value of 28.9 MPa). Application of the resilient TSA abutment results in more equal distribution of stress and deformations in the bone tissue under vertical forces. These values are many times lower than in the model with the non-resilient abutment.

Growth patterns and life-history strategies in Placodontia (Diapsida: Sauropterygia)

PubMed Central

Klein, Nicole; Neenan, James M.; Scheyer, Torsten M.; Griebeler, Eva Maria

2015-01-01

Placodontia is a clade of durophagous, near shore marine reptiles from Triassic sediments of modern-day Europe, Middle East and China. Although much is known about their primary anatomy and palaeoecology, relatively little has been published regarding their life history, i.e. ageing, maturation and growth. Here, growth records derived from long bone histological data of placodont individuals are described and modelled to assess placodont growth and life-history strategies. Growth modelling methods are used to confirm traits documented in the growth record (age at onset of sexual maturity, age when asymptotic length was achieved, age at death, maximum longevity) and also to estimate undocumented traits. Based on these growth models, generalized estimates of these traits are established for each taxon. Overall differences in bone tissue types and resulting growth curves indicate different growth patterns and life-history strategies between different taxa of Placodontia. Psephoderma and Paraplacodus grew with lamellar-zonal bone tissue type and show growth patterns as seen in modern reptiles. Placodontia indet. aff. Cyamodus and some Placodontia indet. show a unique combination of fibrolamellar bone tissue regularly stratified by growth marks, a pattern absent in modern sauropsids. The bone tissue type of Placodontia indet. aff. Cyamodus and Placodontia indet. indicates a significantly increased basal metabolic rate when compared with modern reptiles. Double lines of arrested growth, non-annual rest lines in annuli, and subcycles that stratify zones suggest high dependence of placodont growth on endogenous and exogenous factors. Histological and modelled differences within taxa point to high individual developmental plasticity but sexual dimorphism in growth patterns and the presence of different taxa in the sample cannot be ruled out. PMID:26587259

Fabrication of Trabecular Bone-Templated Tissue-Engineered Constructs by 3D Inkjet Printing.

PubMed

Vanderburgh, Joseph P; Fernando, Shanik J; Merkel, Alyssa R; Sterling, Julie A; Guelcher, Scott A

2017-11-01

3D printing enables the creation of scaffolds with precisely controlled morphometric properties for multiple tissue types, including musculoskeletal tissues such as cartilage and bone. Computed tomography (CT) imaging has been combined with 3D printing to fabricate anatomically scaled patient-specific scaffolds for bone regeneration. However, anatomically scaled scaffolds typically lack sufficient resolution to recapitulate the <100 micrometer-scale trabecular architecture essential for investigating the cellular response to the morphometric properties of bone. In this study, it is hypothesized that the architecture of trabecular bone regulates osteoblast differentiation and mineralization. To test this hypothesis, human bone-templated 3D constructs are fabricated via a new micro-CT/3D inkjet printing process. It is shown that this process reproducibly fabricates bone-templated constructs that recapitulate the anatomic site-specific morphometric properties of trabecular bone. A significant correlation is observed between the structure model index (a morphometric parameter related to surface curvature) and the degree of mineralization of human mesenchymal stem cells, with more concave surfaces promoting more extensive osteoblast differentiation and mineralization compared to predominately convex surfaces. These findings highlight the significant effects of trabecular architecture on osteoblast function. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MRI-guided attenuation correction in whole-body PET/MR: assessment of the effect of bone attenuation.

PubMed

Akbarzadeh, A; Ay, M R; Ahmadian, A; Alam, N Riahi; Zaidi, H

2013-02-01

Hybrid PET/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data. This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps. The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8% in the body and up to 31.0% for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15% for lesions located in the body and 30.7% for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30% of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems. Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies.

Chitosan-poly(lactide-co-glycolide) microsphere-based scaffolds for bone tissue engineering: in vitro degradation and in vivo bone regeneration studies.

PubMed

Jiang, Tao; Nukavarapu, Syam P; Deng, Meng; Jabbarzadeh, Ehsan; Kofron, Michelle D; Doty, Stephen B; Abdel-Fattah, Wafa I; Laurencin, Cato T

2010-09-01

Natural polymer chitosan and synthetic polymer poly(lactide-co-glycolide) (PLAGA) have been investigated for a variety of tissue engineering applications. We have previously reported the fabrication and in vitro evaluation of a novel chitosan/PLAGA sintered microsphere scaffold for load-bearing bone tissue engineering applications. In this study, the in vitro degradation characteristics of the chitosan/PLAGA scaffold and the in vivo bone formation capacity of the chitosan/PLAGA-based scaffolds in a rabbit ulnar critical-sized-defect model were investigated. The chitosan/PLAGA scaffold showed slower degradation than the PLAGA scaffold in vitro. Although chitosan/PLAGA scaffold showed a gradual decrease in compressive properties during the 12-week degradation period, the compressive strength and compressive modulus remained in the range of human trabecular bone. Chitosan/PLAGA-based scaffolds were able to guide bone formation in a rabbit ulnar critical-sized-defect model. Microcomputed tomography analysis demonstrated that successful bridging of the critical-sized defect on the sides both adjacent to and away from the radius occurred using chitosan/PLAGA-based scaffolds. Immobilization of heparin and recombinant human bone morphogenetic protein-2 on the chitosan/PLAGA scaffold surface promoted early bone formation as evidenced by complete bridging of the defect along the radius and significantly enhanced mechanical properties when compared to the chitosan/PLAGA scaffold. Furthermore, histological analysis suggested that chitosan/PLAGA-based scaffolds supported normal bone formation via intramembranous formation. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Factors Affecting the Longevity and Strength in an In Vitro Model of the Bone–Ligament Interface

PubMed Central

Paxton, Jennifer Z.; Donnelly, Kenneth; Keatch, Robert P.; Grover, Liam M.

2010-01-01

The interfaces between musculoskeletal tissues with contrasting moduli are morphologically and biochemically adapted to allow the transmission of force with minimal injury. Current methods of tissue engineering ligaments and tendons do not include the interface and this may limit the future clinical success of engineered musculoskeletal tissues. This study aimed to use solid brushite cement anchors to engineer intact ligaments from bone-to-bone, creating a functional musculoskeletal interface in vitro. We show here that modifying anchor shape and cement composition can alter both the longevity and the strength of an in vitro model of the bone–ligament interface: with values reaching 23 days and 21.6 kPa, respectively. These results validate the use of brushite bone cement to engineer the bone–ligament interface in vitro and raise the potential for future use in ligament replacement surgery. PMID:20431953

Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

PubMed

Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

2014-10-01

Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

Non-invasive assessment of bone quantity and quality in human trabeculae using scanning ultrasound imaging

NASA Astrophysics Data System (ADS)

Xia, Yi

Fractures and associated bone fragility induced by osteoporosis and osteopenia are widespread health threat to current society. Early detection of fracture risk associated with bone quantity and quality is important for both the prevention and treatment of osteoporosis and consequent complications. Quantitative ultrasound (QUS) is an engineering technology for monitoring bone quantity and quality of humans on earth and astronauts subjected to long duration microgravity. Factors currently limiting the acceptance of QUS technology involve precision, accuracy, single index and standardization. The objective of this study was to improve the accuracy and precision of an image-based QUS technique for non-invasive evaluation of trabecular bone quantity and quality by developing new techniques and understanding ultrasound/tissue interaction. Several new techniques have been developed in this dissertation study, including the automatic identification of irregular region of interest (iROI) in bone, surface topology mapping (STM) and mean scattering spacing (MSS) estimation for evaluating trabecular bone structure. In vitro results have shown that (1) the inter- and intra-observer errors in QUS measurement were reduced two to five fold by iROI compared to previous results; (2) the accuracy of QUS parameter, e.g., ultrasound velocity (UV) through bone, was improved 16% by STM; and (3) the averaged trabecular spacing can be estimated by MSS technique (r2=0.72, p<0.01). The measurement errors of BUA and UV introduced by the soft tissue and cortical shells in vivo can be quantified by developed foot model and simplified cortical-trabecular-cortical sandwich model, which were verified by the experimental results. The mechanisms of the errors induced by the cortical and soft tissues were revealed by the model. With developed new techniques and understanding of sound-tissue interaction, in vivo clinical trail and bed rest study were preformed to evaluate the performance of QUS in clinical applications. It has been demonstrated that the QUS has similar performance for in vivo bone density measurement compared to current gold-standard method, i.e., DXA, while additional information are obtained by the QUS for predicting fracture risk by monitoring of bone's quality. The developed QUS imaging technique can be used to assess bone's quantity and quality with improved accuracy and precision.

Recent insights on applications of pullulan in tissue engineering.

PubMed

Singh, Ram Sarup; Kaur, Navpreet; Rana, Vikas; Kennedy, John F

2016-11-20

Tissue engineering is a recently emerging line of act which assists the regeneration of damaged tissues, unable to self-repair themselves and in turn, enhances the natural healing potential of patients. The repair of injured tissue can be induced with the help of some artificially created polymer scaffolds for successful tissue regeneration. The pullulan composite scaffolds can be used to enhance the proliferation and differentiation of cells for tissue regeneration. The unique pattern of pullulan with α-(1→4) and α-(1→6) linkages along with the presence of nine hydroxyl groups on its surface, endows the polymer with distinctive physical features required for tissue engineering. Pullulan can be used for vascular engineering, bone repair and skin tissue engineering. Pullulan composite scaffolds can also be used for treatment of injured femoral condyle bone, skull bone and full thickness skin wound of murine models, transversal mandibular and tibial osteotomy in goat, etc. This review article highlights the latest developments on applications of pullulan and its derivatives in tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model.

PubMed

Ge, Zigang; Tian, Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo, Jin Fei; Cao, Tong

2009-04-01

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models.

Dental pulp stem cells for in vivo bone regeneration: a systematic review of literature.

PubMed

Morad, Golnaz; Kheiri, Lida; Khojasteh, Arash

2013-12-01

This review of literature was aimed to assess in vivo experiments which have evaluated the efficacy of dental pulp stem cells (DPSCs) for bone regeneration. An electronic search of English-language papers was conducted on PubMed database. Studies that assessed the use of DPSCs in bone regeneration in vivo were included and experiments evaluating regeneration of hard tissues other than bone were excluded. The retrieved articles were thoroughly reviewed according to the source of stem cell, cell carrier, the in vivo experimental model, defect type, method of evaluating bone regeneration, and the obtained results. Further assessment of the results was conducted by classifying the studies based on the defect type. Seventeen papers formed the basis of this systematic review. Sixteen out of 17 experiments were performed on animal models with mouse and rat being the most frequently used animal models. Seven out of 17 animal studies, contained subcutaneous pockets on back of the animal for stem cell implantation. In only one study hard tissue formation was not observed. Other types of defects used in the retrieved studies, included cranial defects and mandibular bone defects, in all of which bone formation was reported. When applied in actual bone defects, DPSCs were capable of regenerating bone. Nevertheless, a precise conclusion regarding the efficiency of DPSCs for bone regeneration is yet to be made, considering the limited number of the in vivo experiments and the heterogeneity within their methods. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

NASA Astrophysics Data System (ADS)

Feng, Kai

Scaffolds that can mimic the structural features of natural extracellular matrix and can deliver biomolecules in a controlled fashion may provide cells with a favorable microenvironment to facilitate tissue regeneration. Biodegradable nanofibrous scaffolds with interconnected pore network have previously been developed in our laboratory to mimic collagen matrix and advantageously support both bone and cartilage regeneration. This dissertation project aims to expand both the structural complexity and the biomolecule delivery capacity of such biomimetic scaffolds for tissue engineering. We first developed a nanofibrous scaffold that can release an antibiotic (doxycycline) with a tunable release rate and a tunable dosage, which was demonstrated to be able to inhibit bacterial growth over a prolonged time period. We then developed a nanofibrous tissue-engineciing scaffold that can release basic fibroblast growth factor (bFGF) in a spatially and temporally controlled fashion. In a mouse subcutaneous implantation model, the bFGF-releasing scaffold was shown to enhance cell penetration, tissue ingrowth and angiogenesis. It was also found that both the dose and the release rate of bFGF play roles in the biologic function of the scaffold. After that, we developed a nanofibrous PLLA scaffold that can release both bone morphogenetic protein 7 (BMP-7) and platelet-derived growth factor (PDGF) with distinct dosages and release kinetics. It was demonstrated that BMP-7 and PDGF could synergistically enhance bone regeneration using a mouse ectopic bone formation model and a rat periodontal fenestration defect regeneration model. The regeneration outcome was dependent on the dosage, the ratio and the release kinetics of the two growth factors. Last, we developed an anisotropic composite scaffold with an upper layer mimicking the superficial zone of cartilage and a lower layer mimicking the middle zone of cartilage. The thin superficial layer was fabricated using an electrospinning technique to support a more parallel ECM orientation to the cartilage surface. The lower layer was fabricated using a phase-separation technique to support a more isotropic ECM distribution. Human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded on this complex scaffold and cultured under chondrogenic conditions. The results showed that the composite scaffold was indeed able to support anisotropic cartilage tissue structure formation.

Bone Density, Microarchitecture, and Tissue Quality Long-term After Kidney Transplant.

PubMed

Pérez-Sáez, María José; Herrera, Sabina; Prieto-Alhambra, Daniel; Nogués, Xavier; Vera, María; Redondo-Pachón, Dolores; Mir, Marisa; Güerri, Roberto; Crespo, Marta; Díez-Pérez, Adolfo; Pascual, Julio

2017-06-01

Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry is used to assess bone health in kidney transplant recipients (KTR). Trabecular bone score and in vivo microindentation are novel techniques that directly measure trabecular microarchitecture and mechanical properties of bone at a tissue level and independently predict fracture risk. We tested the bone status of long-term KTR using all 3 techniques. Cross-sectional study including 40 KTR with more than 10 years of follow-up and 94 healthy nontransplanted subjects as controls. Bone mineral density was measured at lumbar spine and the hip. Trabecular bone score was measured by specific software on the dual-energy x-ray absorptiometry scans of lumbar spine in 39 KTR and 77 controls. Microindentation was performed at the anterior tibial face with a reference-point indenter device. Bone measurements were standardized as percentage of a reference value, expressed as bone material strength index (BMSi) units. Multivariable (age, sex, and body mass index-adjusted) linear regression models were fitted to study the association between KTR and BMD/BMSi/trabecular bone score. Bone mineral density was lower at lumbar spine (0.925 ± 0.15 vs 0.982 ± 0.14; P = 0.025), total hip (0.792 ± 0.14 vs 0.902 ± 0.13; P < 0.001), and femoral neck (0.667 ± 0.13 vs 0.775 ± 0.12; P < 0.001) in KTR than in controls. BMSi was also lower in KTR (79.1 ± 7.7 vs 82.9 ± 7.8; P = 0.012) although this difference disappeared after adjusted model (P = 0.145). Trabecular bone score was borderline lower (1.21 ± 0.14 vs 1.3 ± 0.15; adjusted P = 0.072) in KTR. Despite persistent decrease in BMD, trabecular microarchitecture and tissue quality remain normal in long-term KTR, suggesting important recovery of bone health.

Analysis of bone-cartilage-stromal progenitor populations in trauma induced and genetic models of heterotopic ossification

PubMed Central

Agarwal, Shailesh; Loder, Shawn; Li, Shuli; Shrestha, Swati; Li, Jon; Zhao, Bin; Mishina, Yuji; James, Aaron; Levi, Benjamin

2016-01-01

Heterotopic ossification (HO), the formation of extra-skeletal bone in soft tissues, is a pathologic process occurring after substantial burns or trauma, or in patients with type I bone morphogenetic protein (BMP) receptor hyperactivating mutations. Identifying the cells responsible for de novo bone formation during adulthood is of critical importance for therapeutic and regenerative purposes. Using a model of trauma-induced HO with hindlimb Achilles’ tenotomy and dorsal burn injury and a genetic non-trauma HO model (Nfatc1-Cre/caAcvr1fl/wt), we demonstrate enrichment of previously defined bone-cartilage-stromal progenitor cells (BCSP: AlphaV+/CD105+/Tie2-/CD45-/Thy1-/6C3-) at the site of HO formation when compared with marrow isolated from the ipsilateral hindlimb, or from tissue of the contralateral, uninjured hindlimb. Upon transplantation into tenotomy sites soon after injury, BCSPs isolated from neonatal mice or developing HO incorporate into the developing lesion in cartilage and bone and express chondrogenic and osteogenic transcription factors. Additionally, BCSPs isolated from developing HO similarly incorporate into new HO lesions upon transplantation. Finally, adventitial cells, but not pericytes, appear to play a supportive role in HO formation. Our findings indicate that BCSPs contribute to de novo bone formation during adulthood and may hold substantial regenerative potential. PMID:27068890

Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice.

PubMed

Hu, Jingchao; Cao, Yu; Xie, Yilin; Wang, Hua; Fan, Zhipeng; Wang, Jinsong; Zhang, Chunmei; Wang, Jinsong; Wu, Chu-Tse; Wang, Songlin

2016-09-09

Periodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model. In the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation. Our study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm(3)) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm(3)) (P < 0.05). The percentage of bone in the periodontium in the hDPSC injection group was 12.8 ± 4.4 %, while it was 17.4 ± 5.3 % in the hDPSC sheet group (P < 0.05). Both hDPSC injection and cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.

An MRI-based leg model used to simulate biomechanical phenomena during cuff algometry: a finite element study.

PubMed

Manafi-Khanian, Bahram; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

2016-03-01

Cuff pressure stimulation is applicable for assessing deep-tissue pain sensitivity by exciting a variety of deep-tissue nociceptors. In this study, the relative transfer of biomechanical stresses and strains from the cuff via the skin to the muscle and the somatic tissue layers around bones were investigated. Cuff pressure was applied on the lower leg at three different stimulation intensities (mild pressure to pain). Three-dimensional finite element models including bones and three different layers of deep tissues were developed based on magnetic resonance images (MRI). The skin indentation maps at mild pressure, pain threshold, and intense painful stimulations were extracted from MRI and applied to the model. The mean stress under the cuff position around tibia was 4.6, 4.9 and around fibula 14.8, 16.4 times greater than mean stress of muscle surface in the same section at pain threshold and intense painful stimulations, respectively. At the same stimulation intensities, the mean strains around tibia were 36.4, 42.3 % and around fibula 32.9, 35.0 %, respectively, of mean strain on the muscle surface. Assuming strain as the ideal stimulus for nociceptors the results suggest that cuff algometry is less capable to challenge the nociceptors of tissues around bones as compared to more superficially located muscles.

Regression and statistical shape model based substitute CT generation for MRI alone external beam radiation therapy from standard clinical MRI sequences.

PubMed

Ghose, Soumya; Greer, Peter B; Sun, Jidi; Pichler, Peter; Rivest-Henault, David; Mitra, Jhimli; Richardson, Haylea; Wratten, Chris; Martin, Jarad; Arm, Jameen; Best, Leah; Dowling, Jason A

2017-10-27

In MR only radiation therapy planning, generation of the tissue specific HU map directly from the MRI would eliminate the need of CT image acquisition and may improve radiation therapy planning. The aim of this work is to generate and validate substitute CT (sCT) scans generated from standard T2 weighted MR pelvic scans in prostate radiation therapy dose planning. A Siemens Skyra 3T MRI scanner with laser bridge, flat couch and pelvic coil mounts was used to scan 39 patients scheduled for external beam radiation therapy for localized prostate cancer. For sCT generation a whole pelvis MRI (1.6 mm 3D isotropic T2w SPACE sequence) was acquired. Patients received a routine planning CT scan. Co-registered whole pelvis CT and T2w MRI pairs were used as training images. Advanced tissue specific non-linear regression models to predict HU for the fat, muscle, bladder and air were created from co-registered CT-MRI image pairs. On a test case T2w MRI, the bones and bladder were automatically segmented using a novel statistical shape and appearance model, while other soft tissues were separated using an Expectation-Maximization based clustering model. The CT bone in the training database that was most 'similar' to the segmented bone was then transformed with deformable registration to create the sCT component of the test case T2w MRI bone tissue. Predictions for the bone, air and soft tissue from the separate regression models were successively combined to generate a whole pelvis sCT. The change in monitor units between the sCT-based plans relative to the gold standard CT plan for the same IMRT dose plan was found to be [Formula: see text] (mean  ±  standard deviation) for 39 patients. The 3D Gamma pass rate was [Formula: see text] (2 mm/2%). The novel hybrid model is computationally efficient, generating an sCT in 20 min from standard T2w images for prostate cancer radiation therapy dose planning and DRR generation.

Regression and statistical shape model based substitute CT generation for MRI alone external beam radiation therapy from standard clinical MRI sequences

NASA Astrophysics Data System (ADS)

Ghose, Soumya; Greer, Peter B.; Sun, Jidi; Pichler, Peter; Rivest-Henault, David; Mitra, Jhimli; Richardson, Haylea; Wratten, Chris; Martin, Jarad; Arm, Jameen; Best, Leah; Dowling, Jason A.

2017-11-01

In MR only radiation therapy planning, generation of the tissue specific HU map directly from the MRI would eliminate the need of CT image acquisition and may improve radiation therapy planning. The aim of this work is to generate and validate substitute CT (sCT) scans generated from standard T2 weighted MR pelvic scans in prostate radiation therapy dose planning. A Siemens Skyra 3T MRI scanner with laser bridge, flat couch and pelvic coil mounts was used to scan 39 patients scheduled for external beam radiation therapy for localized prostate cancer. For sCT generation a whole pelvis MRI (1.6 mm 3D isotropic T2w SPACE sequence) was acquired. Patients received a routine planning CT scan. Co-registered whole pelvis CT and T2w MRI pairs were used as training images. Advanced tissue specific non-linear regression models to predict HU for the fat, muscle, bladder and air were created from co-registered CT-MRI image pairs. On a test case T2w MRI, the bones and bladder were automatically segmented using a novel statistical shape and appearance model, while other soft tissues were separated using an Expectation-Maximization based clustering model. The CT bone in the training database that was most ‘similar’ to the segmented bone was then transformed with deformable registration to create the sCT component of the test case T2w MRI bone tissue. Predictions for the bone, air and soft tissue from the separate regression models were successively combined to generate a whole pelvis sCT. The change in monitor units between the sCT-based plans relative to the gold standard CT plan for the same IMRT dose plan was found to be 0.3%+/-0.9% (mean  ±  standard deviation) for 39 patients. The 3D Gamma pass rate was 99.8+/-0.00 (2 mm/2%). The novel hybrid model is computationally efficient, generating an sCT in 20 min from standard T2w images for prostate cancer radiation therapy dose planning and DRR generation.

In vivo investigation of tissue-engineered periosteum for the repair of allogeneic critical size bone defects in rabbits.

PubMed

Zhao, Lin; Zhao, Junli; Yu, Jiajia; Sun, Rui; Zhang, Xiaofeng; Hu, Shuhua

2017-04-01

The aim of the study was to evaluate the efficacy of tissue-engineered periosteum (TEP) in repairing allogenic bone defects in the long term. TEP was biofabricated with osteoinduced rabbit bone marrow mesenchymal stem cells and porcine small intestinal submucosa (SIS). A total of 24 critical sized defects were created bilaterally in radii of 12 New Zealand White rabbits. TEP/SIS was implanted into the defect site. Bone defect repair was evaluated with radiographic and histological examination at 4, 8 and 12 weeks. Bone defects were structurally reconstructed in the TEP group with mature cortical bone and medullary canals, however this was not observed in the SIS group at 12 weeks. The TEP approach can effectively restore allogenic critical sized defects, and achieve maturity of long-bone structure in 12 weeks in rabbit models.

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.

Effects of Plantar Vibration on Bone and Deep Fascia in a Rat Hindlimb Unloading Model of Disuse

PubMed Central

Huang, Yunfei; Fan, Yubo; Salanova, Michele; Yang, Xiao; Sun, Lianwen; Blottner, Dieter

2018-01-01

The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, limited information is available on deep fascia in relation to bone in disuse. We used rat hindlimb unloading as a model of disuse (21 days of hindlimb unloading) to study biomechanical property as well as cell and tissue changes to deep fascia and bone unloading. Rats were randomly divided into three groups (n = 8, each): hindlimb unloading (HU), HU + vibration (HUV), and cage-control (CON). The HUV group received local vibration applied to the plantar of both hind paws. Micro-computed tomography analyzed decreased bone mineral density (BMD) of vertebra, tibia, and femur in HU vs. CON. Biomechanical parameters (elastic modulus, max stress, yield stress) of spinal and crural fascia in HU were always increased vs. CON. Vibration in HUV only counteracted HU-induced tibia bone loss and crural fascia mechanical changes but failed to show comparable changes in the vertebra and spinal fascia on lumbar back. Tissue and cell morphometry (size and cell nuclear density), immunomarker intensity levels of anti-collagen-I and III, probed on fascia cryosections well correlated with biomechanical changes suggesting crural fascia a prime target for plantar vibration mechano-stimulation in the HU rat. We conclude that the regular biomechanical characteristics as well as tissue and cell properties in crural fascia and quality of tibia bone (BMD) were preserved by local plantar vibration in disuse suggesting common mechanisms in fascia and bone adaptation to local mechanovibration stimulation following hind limb unloading in the HUV rat. PMID:29875702

Effects of Plantar Vibration on Bone and Deep Fascia in a Rat Hindlimb Unloading Model of Disuse.

PubMed

Huang, Yunfei; Fan, Yubo; Salanova, Michele; Yang, Xiao; Sun, Lianwen; Blottner, Dieter

2018-01-01

The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, limited information is available on deep fascia in relation to bone in disuse. We used rat hindlimb unloading as a model of disuse (21 days of hindlimb unloading) to study biomechanical property as well as cell and tissue changes to deep fascia and bone unloading. Rats were randomly divided into three groups ( n = 8, each): hindlimb unloading (HU), HU + vibration (HUV), and cage-control (CON). The HUV group received local vibration applied to the plantar of both hind paws. Micro-computed tomography analyzed decreased bone mineral density (BMD) of vertebra, tibia, and femur in HU vs. CON. Biomechanical parameters (elastic modulus, max stress, yield stress) of spinal and crural fascia in HU were always increased vs. CON. Vibration in HUV only counteracted HU-induced tibia bone loss and crural fascia mechanical changes but failed to show comparable changes in the vertebra and spinal fascia on lumbar back. Tissue and cell morphometry (size and cell nuclear density), immunomarker intensity levels of anti-collagen-I and III, probed on fascia cryosections well correlated with biomechanical changes suggesting crural fascia a prime target for plantar vibration mechano-stimulation in the HU rat. We conclude that the regular biomechanical characteristics as well as tissue and cell properties in crural fascia and quality of tibia bone (BMD) were preserved by local plantar vibration in disuse suggesting common mechanisms in fascia and bone adaptation to local mechanovibration stimulation following hind limb unloading in the HUV rat.

Mixed reality temporal bone surgical dissector: mechanical design.

PubMed

Hochman, Jordan Brent; Sepehri, Nariman; Rampersad, Vivek; Kraut, Jay; Khazraee, Milad; Pisa, Justyn; Unger, Bertram

2014-08-08

The Development of a Novel Mixed Reality (MR) Simulation. An evolving training environment emphasizes the importance of simulation. Current haptic temporal bone simulators have difficulty representing realistic contact forces and while 3D printed models convincingly represent vibrational properties of bone, they cannot reproduce soft tissue. This paper introduces a mixed reality model, where the effective elements of both simulations are combined; haptic rendering of soft tissue directly interacts with a printed bone model. This paper addresses one aspect in a series of challenges, specifically the mechanical merger of a haptic device with an otic drill. This further necessitates gravity cancelation of the work assembly gripper mechanism. In this system, the haptic end-effector is replaced by a high-speed drill and the virtual contact forces need to be repositioned to the drill tip from the mid wand. Previous publications detail generation of both the requisite printed and haptic simulations. Custom software was developed to reposition the haptic interaction point to the drill tip. A custom fitting, to hold the otic drill, was developed and its weight was offset using the haptic device. The robustness of the system to disturbances and its stable performance during drilling were tested. The experiments were performed on a mixed reality model consisting of two drillable rapid-prototyped layers separated by a free-space. Within the free-space, a linear virtual force model is applied to simulate drill contact with soft tissue. Testing illustrated the effectiveness of gravity cancellation. Additionally, the system exhibited excellent performance given random inputs and during the drill's passage between real and virtual components of the model. No issues with registration at model boundaries were encountered. These tests provide a proof of concept for the initial stages in the development of a novel mixed-reality temporal bone simulator.

Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain.

PubMed

Bosy-Westphal, Anja; Later, Wiebke; Schautz, Britta; Lagerpusch, Merit; Goele, Kristin; Heller, Martin; Glüer, Claus-C; Müller, Manfred J

2011-07-01

Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.

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.

Guiding bone formation in a critical-sized defect and assessments.

PubMed

Jannetty, Joseph; Kolb, Eric; Boxberger, John; Deslauriers, Richard; Ganey, Timothy

2010-11-01

Development of alternatives to autologous bone has been served by many hypotheses and developments. Favorable properties of synthetic materials used currently in bone grafting support tissue differentiation without shielding capacity for integrated modeling. Ideally, new materials provide tissue compatibility and minimize patient morbidity and are attractive because of potential for in situ delivery, isothermal polymerization, porous structure, and nontoxic chemistry. For application in cranial bone, ability for materials to be laid adjacent to brain and offer postsurgical protection without neural risk is a critical asset. Kryptonite Bone Cement (KBC) meets the property criteria for cranial bone repair with regard to adhesive, conductive, and biologic transparency and US Food and Drug Administration approval for cranial bone void repair. To better delineate the morphology effective in cranial bone repair, a comparison was made between KBC and BoneSource, another material approved for the same indication. After Institutional Animal Care and Use Committee approval, the study assessed 24 rabbits, each with 2 separate cranial implants, to evaluate integration and absorption of the biomaterial at defined time points of 12, 18, 24, and 36 weeks. The 36-week assessment demonstrated near-complete resorption/integration of the BoneSource graft material. Bone was present within the biomaterial as well as independent of contact. The KBC was similarly integrated throughout the mass of the material, and new bone was in contact with the grafting material and also seen as separate islands of new bone. The bone demonstrated lamellar bone architecture with clear trabecular morphology. At higher magnification, the bone architecture can be clearly delineated, and comparison between the graft fillers is not obvious relative to the bone that has formed. Despite microscopic similarities, the most striking difference was maintenance of scaffold anatomy during bone regeneration. Kryptonite Bone Cement meets the criteria described in the introduction; properties of biologic transparency, osteoconductivity, and ergonomic utility offer other potential uses in bone repair. Key tenets of bone tissue regeneration observed in this analysis included adequate cell differentiation and tissue support. Bone that formed demonstrated lamellar rather than woven bone to suggest response to loading strain rather than merely biochemical precipitation. Over the 36-week study, the graft showed progressive bioabsorbable potential with calibrated replacement.

Inter-species investigation of the mechano-regulation of bone healing: comparison of secondary bone healing in sheep and rat.

PubMed

Checa, Sara; Prendergast, Patrick J; Duda, Georg N

2011-04-29

Inter-species differences in regeneration exist in various levels. One aspect is the dynamics of bone regeneration and healing, e.g. small animals show a faster healing response when compared to large animals. Mechanical as well as biological factors are known to play a key role in the process. However, it remains so far unknown whether different animals follow at all comparable mechano-biological rules during tissue regeneration, and in particular during bone healing. In this study, we investigated whether differences observed in vivo in the dynamics of bone healing between rat and sheep are only due to differences in the animal size or whether these animals have a different mechano-biological response during the healing process. Histological sections from in vivo experiments were compared to in silico predictions of a mechano-biological computer model for the simulation of bone healing. Investigations showed that the healing processes in both animal models occur under significantly different levels of mechanical stimuli within the callus region, which could explain histological observations of early intramembranous ossification at the endosteal side. A species-specific adaptation of a mechano-biological model allowed a qualitative match of model predictions with histological observations. Specifically, when keeping cell activity processes at the same rate, the amount of tissue straining defining favorable mechanical conditions for the formation of bone had to be increased in the large animal model, with respect to the small animal, to achieve a qualitative agreement of model predictions with histological data. These findings illustrate that geometrical (size) differences alone cannot explain the distinctions seen in the histological appearance of secondary bone healing in sheep and rat. It can be stated that significant differences in the mechano-biological regulation of the healing process exist between these species. Future investigations should aim towards understanding whether these differences are due to differences in cell behavior, material properties of the newly formed tissues within the callus and/or differences in response to the mechanical environment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

PubMed Central

Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

2014-01-01

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

Simulating thermal effects of MR-guided focused ultrasound in cortical bone and its surrounding tissue.

PubMed

Hudson, Thomas J; Looi, Thomas; Pichardo, Samuel; Amaral, Joao; Temple, Michael; Drake, James M; Waspe, Adam C

2018-02-01

Magnetic resonance-guided focused ultrasound (MRgFUS) is emerging as a treatment alternative for osteoid osteoma and painful bone metastases. This study describes a new simulation platform that predicts the distribution of heat generated by MRgFUS when applied to bone tissue. Calculation of the temperature distribution was performed using two mathematical models. The first determined the propagation and absorption of acoustic energy through each medium, and this was performed using a multilayered approximation of the Rayleigh integral method. The ultrasound energy distribution derived from these equations could then be converted to heat energy, and the second mathematical model would then use the heat generated to determine the final temperature distribution using a finite-difference time-domain application of Pennes' bio-heat transfer equation. Anatomical surface geometry was generated using a modified version of a mesh-based semiautomatic segmentation algorithm, and both the acoustic and thermodynamic models were calculated using a parallelized algorithm running on a graphics processing unit (GPU) to greatly accelerate computation time. A series of seven porcine experiments were performed to validate the model, comparing simulated temperatures to MR thermometry and assessing spatial, temporal, and maximum temperature accuracy in the soft tissue. The parallelized algorithm performed acoustic and thermodynamic calculations on grids of over 10 8 voxels in under 30 s for a simulated 20 s of heating and 40 s of cooling, with a maximum time per calculated voxel of less than 0.3 μs. Accuracy was assessed by comparing the soft tissue thermometry to the simulation in the soft tissue adjacent to bone using four metrics. The maximum temperature difference between the simulation and thermometry in a region of interest around the bone was measured to be 5.43 ± 3.51°C average absolute difference and a percentage difference of 16.7%. The difference in heating location resulted in a total root-mean-square error of 4.21 ± 1.43 mm. The total size of the ablated tissue calculated from the thermal dose approximation in the simulation was, on average, 67.6% smaller than measured from the thermometry. The cooldown was much faster in the simulation, where it decreased by 14.22 ± 4.10°C more than the thermometry in 40 s after sonication ended. The use of a Rayleigh-based acoustic model combined with a discretized bio-heat transfer model provided a rapid three-dimensional calculation of the temperature distribution through bone and soft tissue during MRgFUS application, and the parallelized GPU algorithm provided the computational speed that would be necessary for an intraoperative treatment planning software platform. © 2017 American Association of Physicists in Medicine.

3D printed alendronate-releasing poly(caprolactone) porous scaffolds enhance osteogenic differentiation and bone formation in rat tibial defects.

PubMed

Kim, Sung Eun; Yun, Young-Pil; Shim, Kyu-Sik; Kim, Hak-Jun; Park, Kyeongsoon; Song, Hae-Ryong

2016-09-29

The aim of this study was to evaluate the in vitro osteogenic effects and in vivo new bone formation of three-dimensional (3D) printed alendronate (Aln)-releasing poly(caprolactone) (PCL) (Aln/PCL) scaffolds in rat tibial defect models. 3D printed Aln/PCL scaffolds were fabricated via layer-by-layer deposition. The fabricated Aln/PCL scaffolds had high porosity and an interconnected pore structure and showed sustained Aln release. In vitro studies showed that MG-63 cells seeded on the Aln/PCL scaffolds displayed increased alkaline phosphatase (ALP) activity and calcium content in a dose-dependent manner when compared with cell cultures in PCL scaffolds. In addition, in vivo animal studies and histologic evaluation showed that Aln/PCL scaffolds implanted in a rat tibial defect model markedly increased new bone formation and mineralized bone tissues in a dose-dependent manner compared to PCL-only scaffolds. Our results show that 3D printed Aln/PCL scaffolds are promising templates for bone tissue engineering applications.

Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+(R), microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits.

PubMed

Jégoux, Franck; Goyenvalle, Eric; Cognet, Ronan; Malard, Olivier; Moreau, Francoise; Daculsi, Guy; Aguado, Eric

2009-12-15

The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

Full-Field Calcium K-Edge X-ray Absorption Near-Edge Structure Spectroscopy on Cortical Bone at the Micron-Scale: Polarization Effects Reveal Mineral Orientation.

PubMed

Hesse, Bernhard; Salome, Murielle; Castillo-Michel, Hiram; Cotte, Marine; Fayard, Barbara; Sahle, Christoph J; De Nolf, Wout; Hradilova, Jana; Masic, Admir; Kanngießer, Birgit; Bohner, Marc; Varga, Peter; Raum, Kay; Schrof, Susanne

2016-04-05

Here, we show results on X-ray absorption near edge structure spectroscopy in both transmission and X-ray fluorescence full-field mode (FF-XANES) at the calcium K-edge on human bone tissue in healthy and diseased conditions and for different tissue maturation stages. We observe that the dominating spectral differences originating from different tissue regions, which are well pronounced in the white line and postedge structures are associated with polarization effects. These polarization effects dominate the spectral variance and must be well understood and modeled before analyzing the very subtle spectral variations related to the bone tissue variations itself. However, these modulations in the fine structure of the spectra can potentially be of high interest to quantify orientations of the apatite crystals in highly structured tissue matrices such as bone. Due to the extremely short wavelengths of X-rays, FF-XANES overcomes the limited spatial resolution of other optical and spectroscopic techniques exploiting visible light. Since the field of view in FF-XANES is rather large the acquisition times for analyzing the same region are short compared to, for example, X-ray diffraction techniques. Our results on the angular absorption dependence were verified by both site-matched polarized Raman spectroscopy, which has been shown to be sensitive to the orientation of bone building blocks and by mathematical simulations of the angular absorbance dependence. As an outlook we further demonstrate the polarization based assessment of calcium-containing crystal orientation and specification of calcium in a beta-tricalcium phosphate (β-Ca3(PO4)2 scaffold implanted into ovine bone. Regarding the use of XANES to assess chemical properties of Ca in human bone tissue our data suggest that neither the anatomical site (tibia vs jaw) nor pathology (healthy vs necrotic jaw bone tissue) affected the averaged spectral shape of the XANES spectra.

Implant platform switching: biomechanical approach using two-dimensional finite element analysis.

PubMed

Tabata, Lucas Fernando; Assunção, Wirley Gonçalves; Adelino Ricardo Barão, Valentim; de Sousa, Edson Antonio Capello; Gomes, Erica Alves; Delben, Juliana Aparecida

2010-01-01

In implant therapy, a peri-implant bone resorption has been noticed mainly in the first year after prosthesis insertion. This bone remodeling can sometimes jeopardize the outcome of the treatment, especially in areas in which short implants are used and also in aesthetic cases. To avoid this occurrence, the use of platform switching (PS) has been used. This study aimed to evaluate the biomechanical concept of PS with relation to stress distribution using two-dimensional finite element analysis. A regular matching diameter connection of abutment-implant (regular platform group [RPG]) and a PS connection (PS group [PSG]) were simulated by 2 two-dimensional finite element models that reproduced a 2-piece implant system with peri-implant bone tissue. A regular implant (prosthetic platform of 4.1 mm) and a wide implant (prosthetic platform of 5.0 mm) were used to represent the RPG and PSG, respectively, in which a regular prosthetic component of 4.1 mm was connected to represent the crown. A load of 100 N was applied on the models using ANSYS software. The RPG spreads the stress over a wider area in the peri-implant bone tissue (159 MPa) and the implant (1610 MPa), whereas the PSG seems to diminish the stress distribution on bone tissue (34 MPa) and implant (649 MPa). Within the limitation of the study, the PS presented better biomechanical behavior in relation to stress distribution on the implant but especially in the bone tissue (80% less). However, in the crown and retention screw, an increase in stress concentration was observed.

A method for continuous monitoring of the Ground Reaction Force during daily activity

NASA Technical Reports Server (NTRS)

Whalen, Robert; Quintana, Jason; Emery, Jeff

1993-01-01

Theoretical models and experimental studies of bone remodeling have identified peak cyclic force levels (or cyclic tissue strain energy density), number of daily loading cycles, and load (strain) rate as possible contributors to bone modeling and remodeling stimulus. To test our theoretical model and further investigate the influence of mechanical forces on bone density, we have focused on the calcaneus as a model site loaded by calcaneal surface tractions which are predominantly determined by the magnitude of the external ground reaction force (GRF).

Histological evolution of the regenerate during bone transport: an experimental study in sheep.

PubMed

López-Pliego, Esperanza Macarena; Giráldez-Sánchez, Miguel Ángel; Mora-Macías, Juan; Reina-Romo, Esther; Domínguez, Jaime

2016-09-01

Bone transport (BT) for segmentary bone defects is a well-known technique as it enables correction with new bone formation, which is similar to the previous bone. Despite the high number of experimental studies of distraction osteogenesis in bone lengthening, the types of ossification and histological changes that occur in the regenerate of the bone transport process remain controversial. The aim of this study is to provide the complete evolution of tissues and the types of ossification in the regenerate during the different phases of bone formation after BT until the end of the remodelling period. A histological study was performed using ten adult sheep that were submitted to BT. The types of ossification as well as the evolution of different tissues in the regenerate were determined using histomorphometry and inmunohistochemical studies. The evolution of trabeculae thickness, osteoblast and osteoclast densities, relationship between collagen types and changes in vascularization were also studied. Ossification was primarily intramembranous, with some focus of endochondral ossification in isolated animals. The cell counts showed a progression of cellular activity from the periphery to the centre, presenting the same progression as the growth of bone trabeculae, whose trabeculae thickness was quadrupled at the end of remodelling. Inmunohistochemical studies confirmed the prevalence of type I collagen and the ratio of the Type I/Type II collagen ratio was found to be 2.48. The percentages of the vascularized areas were proximally higher than distally in all animals, but distal zone obtained higher rates than the central region. Bone transport regenerate exhibits a centripetal ossification model and a mixed pattern with predominance of intramembranous over endochondral ossification. The data obtained resemble partially to those found in models of bone lengthening applied to large animals. This study provides a detailed structural characterization of the newly formed tissue, which may help to explain the development of the regenerate of bone transport in humans. It will also serve for future mechanobiological models that may aid research on the effect of loading or distractor stiffness in clinical results. © 2016 Elsevier Ltd. All rights reserved.

Characterization of Focal Muscle Compression Under Impact Loading

NASA Astrophysics Data System (ADS)

Butler, Ben; Sory, David; Nguyen, Thuy-Tien; Curry, Richard; Clasper, Jon; Proud, William; Williams, Alun; Brown, Kate

2015-06-01

The pattern of battle injuries sustained in modern wars shows that over 70% of combat wounds are to the extremities. These injuries are characterized by disruption and contamination of the limb soft tissue envelope. The extent of this tissue trauma and contamination determine the outcome in extremity injury. In military injury, common post-traumatic complications at amputation sites include heterotopic ossification (formation of bone in soft tissue), and severe soft tissue and bone infections. We are currently developing a model of soft tissue injury that recreates pathologies observed in combat injuries. Here we present characterization of a controlled focal compression of the rabbit flexor carpi ulnaris (FCU) muscle group. The FCU was previously identified as a suitable site for studying impact injury because its muscle belly can easily be mobilized from the underlying bone without disturbing anatomical alignment in the limb. We show how macroscopic changes in tissue organization, as visualized using optical microscopy, can be correlated with data from temporally resolved traces of loading conditions. Funding provided by the Royal British Legion.

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

PubMed

Thangarajah, Tanujan; Shahbazi, Shirin; Pendegrass, Catherine J; Lambert, Simon; Alexander, Susan; Blunn, Gordon W

2016-01-01

Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft.

The contribution of solid-state NMR spectroscopy to understanding biomineralization: Atomic and molecular structure of bone

NASA Astrophysics Data System (ADS)

Duer, Melinda J.

2015-04-01

Solid-state NMR spectroscopy has had a major impact on our understanding of the structure of mineralized tissues, in particular bone. Bone exemplifies the organic-inorganic composite structure inherent in mineralized tissues. The organic component of the extracellular matrix in bone is primarily composed of ordered fibrils of collagen triple-helical molecules, in which the inorganic component, calcium phosphate particles, composed of stacks of mineral platelets, are arranged around the fibrils. This perspective argues that key factors in our current structural model of bone mineral have come about through NMR spectroscopy and have yielded the primary information on how the mineral particles interface and bind with the underlying organic matrix. The structure of collagen within the organic matrix of bone or any other structural tissue has yet to be determined, but here too, this perspective shows there has been real progress made through application of solid-state NMR spectroscopy in conjunction with other techniques. In particular, NMR spectroscopy has highlighted the fact that even within these structural proteins, there is considerable dynamics, which suggests that one should be cautious when using inherently static structural models, such as those arising from X-ray diffraction analyses, to gain insight into molecular roles. It is clear that the NMR approach is still in its infancy in this area, and that we can expect many more developments in the future, particularly in understanding the molecular mechanisms of bone diseases and ageing.

Natural Polymer-Cell Bioconstructs for Bone Tissue Engineering.

PubMed

Titorencu, Irina; Albu, Madalina Georgiana; Nemecz, Miruna; Jinga, Victor V

2017-01-01

The major goal of bone tissue engineering is to develop bioconstructs which substitute the functionality of damaged natural bone structures as much as possible if critical-sized defects occur. Scaffolds that mimic the structure and composition of bone tissue and cells play a pivotal role in bone tissue engineering applications. First, composition, properties and in vivo synthesis of bone tissue are presented for the understanding of bone formation. Second, potential sources of osteoprogenitor cells have been investigated for their capacity to induce bone repair and regeneration. Third, taking into account that the main property to qualify one scaffold as a future bioconstruct for bone tissue engineering is the biocompatibility, the assessments which prove it are reviewed in this paper. Forth, various types of natural polymer- based scaffolds consisting in proteins, polysaccharides, minerals, growth factors etc, are discussed, and interaction between scaffolds and cells which proved bone tissue engineering concept are highlighted. Finally, the future perspectives of natural polymer-based scaffolds for bone tissue engineering are considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microcomputed tomography characterization of neovascularization in bone tissue engineering applications.

PubMed

Young, Simon; Kretlow, James D; Nguyen, Charles; Bashoura, Alex G; Baggett, L Scott; Jansen, John A; Wong, Mark; Mikos, Antonios G

2008-09-01

Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs.

Solid Free-form Fabrication Technology and Its Application to Bone Tissue Engineering

PubMed Central

Lee, Jin Woo; Kim, Jong Young; Cho, Dong-Woo

2010-01-01

The development of scaffolds for use in cell-based therapies to repair damaged bone tissue has become a critical component in the field of bone tissue engineering. However, design of scaffolds using conventional fabrication techniques has limited further advancement, due to a lack of the required precision and reproducibility. To overcome these constraints, bone tissue engineers have focused on solid free-form fabrication (SFF) techniques to generate porous, fully interconnected scaffolds for bone tissue engineering applications. This paper reviews the potential application of SFF fabrication technologies for bone tissue engineering with respect to scaffold fabrication. In the near future, bone scaffolds made using SFF apparatus should become effective therapies for bone defects. PMID:24855546

Tissue-engineered vascularized bone grafts: basic science and clinical relevance to trauma and reconstructive microsurgery.

PubMed

Johnson, Elizabeth O; Troupis, Theodore; Soucacos, Panayotis N

2011-03-01

Bone grafts are an important part of orthopaedic surgeon's armamentarium. Despite well-established bone-grafting techniques, large bone defects still represent a challenge. Efforts have therefore been made to develop osteoconductive, osteoinductive, and osteogenic bone-replacement systems. The long-term clinical goal in bone tissue engineering is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. Current bone tissue engineering strategies take into account that bone is known for its ability to regenerate following injury, and for its intrinsic capability to re-establish a complex hierarchical structure during regeneration. Although the tissue engineering of bone for the reconstruction of small to moderate sized bone defects technically feasible, the reconstruction of large defects remains a daunting challenge. The essential steps towards optimized clinical application of tissue-engineered bone are dependent upon recent advances in the area of neovascularization of the engineered construct. Despite these recent advances, however, a gap from bench to bedside remains; this may ultimately be bridged by a closer collaboration between basic scientists and reconstructive surgeons. The aim of this review is to introduce the basic principles of tissue engineering of bone, outline the relevant bone physiology, and discuss the recent concepts for the induction of vascularization in engineered bone tissue. Copyright © 2011 Wiley-Liss, Inc.

Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

PubMed

Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

2011-08-01

Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging.

PubMed

Yang, Haisheng; Albiol, Laia; Chan, Wing-Lee; Wulsten, Dag; Seliger, Anne; Thelen, Michael; Thiele, Tobias; Spevak, Lyudmila; Boskey, Adele; Kornak, Uwe; Checa, Sara; Willie, Bettina M

2017-12-08

Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (Gorab Prx1 ) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the Gorab Prx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that Gorab Prx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared (FTIR) imaging indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the Gorab Prx1 tibiae (p < .05), suggesting delayed mineralization. In vivo strain gauge measurement and finite element analysis showed ∼two times higher tissue-level strains within the Gorab Prx1 tibiae relative to LC tibiae when subjected to axial compressive loads of the same magnitude. Three-point bending tests suggested that Gorab Prx1 tibiae were weaker and more brittle, as indicated by decreasing whole-bone strength (46%), stiffness (55%), work-to-fracture (61%) and post-yield displacement (47%). Many of these morphological and biomechanical characteristics of the Gorab Prx1 tibia recapitulated changes in other animal models of skeletal aging. Future studies are necessary to confirm how our observations might guide the way to a better understanding and treatment of GO. Copyright © 2017 Elsevier Ltd. All rights reserved.

Geometry Design Optimization of Functionally Graded Scaffolds for Bone Tissue Engineering: A Mechanobiological Approach.

PubMed

Boccaccio, Antonio; Uva, Antonio Emmanuele; Fiorentino, Michele; Mori, Giorgio; Monno, Giuseppe

2016-01-01

Functionally Graded Scaffolds (FGSs) are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young's modulus values. For each combination of these variables, the explicit equation of the porosity distribution law-i.e the law that describes the pore dimensions in function of the spatial coordinates-was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards optimizing geometry of functionally graded scaffolds based on mechanobiological criteria.

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

The supramolecular structure of bone: X-ray scattering analysis and lateral structure modeling

PubMed Central

Zhou, Hong-Wen; Burger, Christian; Wang, Hao; Hsiao, Benjamin S.; Chu, Benjamin; Graham, Lila

2016-01-01

The evolution of vertebrates required a key development in supramolecular evolution: internally mineralized collagen fibrils. In bone, collagen molecules and mineral crystals form a nanocomposite material comparable to cast iron in tensile strength, but several times lighter and more flexible. Current understanding of the internal nanoscale structure of collagen fibrils, derived from studies of rat tail tendon (RTT), does not explain how nucleation and growth of mineral crystals can occur inside a collagen fibril. Experimental obstacles encountered in studying bone have prevented a solution to this problem for several decades. This report presents a lateral packing model for collagen molecules in bone fibrils, based on the unprecedented observation of multiple resolved equatorial reflections for bone tissue using synchrotron small-angle X-ray scattering (SAXS; ∼1 nm resolution). The deduced structure for pre-mineralized bone fibrils includes features that are not present in RTT: spatially discrete microfibrils. The data are consistent with bone microfibrils similar to pentagonal Smith microfibrils, but are not consistent with the (nondiscrete) quasi-hexagonal microfibrils reported for RTT. These results indicate that collagen fibrils in bone and tendon differ in their internal structure in a manner that allows bone fibrils, but not tendon fibrils, to internally mineralize. In addition, the unique pattern of collagen cross-link types and quantities in mineralized tissues can be can be accounted for, in structural/functional terms, based on a discrete microfibril model. PMID:27599731

Using eddy currents for noninvasive in vivo pH monitoring for bone tissue engineering.

PubMed

Beck-Broichsitter, Benedicta E; Daschner, Frank; Christofzik, David W; Knöchel, Reinhard; Wiltfang, Jörg; Becker, Stephan T

2015-03-01

The metabolic processes that regulate bone healing and bone induction in tissue engineering models are not fully understood. Eddy current excitation is widely used in technical approaches and in the food industry. The aim of this study was to establish eddy current excitation for monitoring metabolic processes during heterotopic osteoinduction in vivo. Hydroxyapatite scaffolds were implanted into the musculus latissimus dorsi of six rats. Bone morphogenetic protein 2 (BMP-2) was applied 1 and 2 weeks after implantation. Weekly eddy current excitation measurements were performed. Additionally, invasive pH measurements were obtained from the scaffolds using fiber optic detection devices. Correlations between the eddy current measurements and the metabolic values were calculated. The eddy current measurements and pH values decreased significantly in the first 2 weeks of the study, followed by a steady increase and stabilization at higher levels towards the end of the study. The measurement curves and statistical evaluations indicated a significant correlation between the resonance frequency values of the eddy current excitation measurements and the observed pH levels (p = 0.0041). This innovative technique was capable of noninvasively monitoring metabolic processes in living tissues according to pH values, showing a direct correlation between eddy current excitation and pH in an in vivo tissue engineering model.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

PubMed

Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

2016-08-01

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering.

PubMed

Hamlet, Stephen M; Vaquette, Cedryck; Shah, Amit; Hutmacher, Dietmar W; Ivanovski, Saso

2017-04-01

Alveolar bone regeneration remains a significant clinical challenge in periodontology and dental implantology. This study assessed the mineralized tissue forming potential of 3-D printed medical grade polycaprolactone (mPCL) constructs containing osteoblasts (OB) encapsulated in a hyaluronic acid (HA)-hydrogel incorporating bone morphogenetic protein-7 (BMP-7). HA-hydrogels containing human OB ± BMP-7 were prepared. Cell viability, osteogenic gene expression, mineralized tissue formation and BMP-7 release in vitro, were assessed by fluorescence staining, RT-PCR, histological/μ-CT examination and ELISA respectively. In an athymic rat model, subcutaneous ectopic mineralized tissue formation in mPCL-hydrogel constructs was assessed by μ-CT and histology. Osteoblast encapsulation in HA-hydrogels did not detrimentally effect cell viability, and 3-D culture in osteogenic media showed mineralized collagenous matrix formation after 6 weeks. BMP-7 release from the hydrogel was biphasic, sustained and increased osteogenic gene expression in vitro. After 4 weeks in vivo, mPCL-hydrogel constructs containing BMP-7 formed significantly more volume (mm 3 ) of vascularized bone-like tissue. Functionalized mPCL-HA hydrogel constructs provide a favourable environment for bone tissue engineering. Although encapsulated cells contributed to mineralized tissue formation within the hydrogel in vitro and in vivo, their addition did not result in an improved outcome compared to BMP-7 alone. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modeling Analysis of Biomechanical Changes of Middle Ear and Cochlea in Otitis Media

NASA Astrophysics Data System (ADS)

Gan, Rong Z.; Zhang, Xiangming; Guan, Xiying

2011-11-01

A comprehensive finite element (FE) model of the human ear including the ear canal, middle ear, and spiral cochlea was developed using histological sections of human temporal bone. The cochlea was modeled with three chambers separated by the basilar membrane and Reissner's membrane and filled with perilymphatic fluid. The viscoelastic material behavior was applied to middle ear soft tissues based on dynamic measurements of tissues in our lab. The model was validated using the experimental data obtained in human temporal bones and then used to simulate various stages of otitis media (OM) including the changes of morphology, mechanical properties, pressure, and fluid level in the middle ear. Function alterations of the middle ear and cochlea in OM were derived from the model and compared with the measurements from temporal bones. This study indicates that OM can be simulated in the FE model to predict the hearing loss induced by biomechanical changes of the middle ear and cochlea.

New microscale constitutive model of human trabecular bone based on depth sensing indentation technique.

PubMed

Pawlikowski, Marek; Jankowski, Krzysztof; Skalski, Konstanty

2018-05-30

A new constitutive model for human trabecular bone is presented in the present study. As the model is based on indentation tests performed on single trabeculae it is formulated in a microscale. The constitutive law takes into account non-linear viscoelasticity of the tissue. The elastic response is described by the hyperelastic Mooney-Rivlin model while the viscoelastic effects are considered by means of the hereditary integral in which stress depends on both time and strain. The material constants in the constitutive equation are identified on the basis of the stress relaxation tests and the indentation tests using curve-fitting procedure. The constitutive model is implemented into finite element package Abaqus ® by means of UMAT subroutine. The curve-fitting error is low and the viscoelastic behaviour of the tissue predicted by the proposed constitutive model corresponds well to the realistic response of the trabecular bone. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Osteoinduction by Ca-P biomaterials implanted into the muscles of mice*

PubMed Central

Yang, Rui-na; Ye, Feng; Cheng, Li-jia; Wang, Jin-jing; Lu, Xiao-feng; Shi, Yu-jun; Fan, Hong-song; Zhang, Xing-dong; Bu, Hong

2011-01-01

The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented, but little research has been performed on rodent animals, e.g., mice. In this study, we report osteoinduction in a mouse model. Thirty mice were divided into two groups. BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle, respectively. Five mice in each group were killed at 15, 30, and 45 d after surgery. Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining, immunohistochemistry (IHC) staining, and Alizarin Red S staining to check bone formation in the biomaterials. Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups. Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation; the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%, respectively. However, we did not see any bone tissue in Sample B until 45 d after implantation. Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2), collagen type I, and osteopontin were detected by IHC staining in Sample A 30 d after implantation. In addition, the newly-formed bone was also confirmed by Alizarin Red S staining. Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available, our results may contribute to further mechanism research. PMID:21726066

The G-factor as a tool to learn more about bone structure and function.

PubMed

Zerath, E

1999-07-01

In normal life on earth, the locomotor system is exposed to two types of stimulation: gravity (passive stimulation) and motion (active stimulation). Both permanently combine, and the interactions between locomotion and gravity induce an overall recruitment which is repeated daily and maintains the bone tissue structure within the range of constraints to which it is adapted. This range is one of the basic hypotheses underlying the mechanical concepts of bone structure control, and it has been considered as logical to assume that weightlessness of spaceflight should produce bone loss since astronauts are outside of the terrestrial gravitational field of forces, no longer relying on muscular work to change positions or move. But, thirty years after the first changes in phospho-calcium metabolism were observed in astronauts after spaceflight, current knowledge does not provide a full understanding of this pathogeny, and prove the G-factor is now considered as an essential component of the experimental tools available to study bone physiology. The study of the physiology of bone tissue usually consists in the investigation of its two fundamental roles, i.e. reservoir of inorganic elements (calcium, phosphorus, magnesium) and mechanical support for soft tissues. Together with the combined action of muscles, tendons, and ligaments, this support permits motion and locomotion. These two functions rely on a sophisticated bone tissue architecture, and on the adaptability of this structure, with modeling and remodeling processes, themselves associated with the coupled activity of specialized bone cell populations.

Synchrotron Ultraviolet Microspectroscopy on Rat Cortical Bone: Involvement of Tyrosine and Tryptophan in the Osteocyte and Its Environment

PubMed Central

Pallu, Stéphane; Rochefort, Gael Y.; Jaffre, Christelle; Refregiers, Matthieu; Maurel, Delphine B.; Benaitreau, Delphine; Lespessailles, Eric; Jamme, Frédéric; Chappard, Christine; Benhamou, Claude-Laurent

2012-01-01

Alcohol induced osteoporosis is characterized by a bone mass decrease and microarchitecture alterations. Having observed an excess in osteocyte apoptosis, we aimed to assess the bone tissue biochemistry, particularly in the osteocyte and its environment. For this purpose, we used a model of alcohol induced osteoporosis in rats. Bone sections of cortical bone were investigated using synchrotron UV-microspectrofluorescence at subcellular resolution. We show that bone present three fluorescence peaks at 305, 333 and 385 nm, respectively corresponding to tyrosine, tryptophan and collagen. We have determined that tyrosine/collagen and tryptophan/collagen ratios were higher in the strong alcohol consumption group. Tryptophan is related to the serotonin metabolism involved in bone formation, while tyrosine is involved in the activity of tyrosine kinases and phosphatases in osteocytes. Our experiment represents the first combined synchrotron UV microspectroscopy analysis of bone tissue with a quantitative biochemical characterization in the osteocyte and surrounding matrix performed separately. PMID:22937127

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

PubMed Central

Nguyen, Lonnissa H.; Annabi, Nasim; Nikkhah, Mehdi; Bae, Hojae; Binan, Loïc; Park, Sangwon; Kang, Yunqing

2012-01-01

Significant advances have been made in bone tissue engineering (TE) in the past decade. However, classical bone TE strategies have been hampered mainly due to the lack of vascularization within the engineered bone constructs, resulting in poor implant survival and integration. In an effort toward clinical success of engineered constructs, new TE concepts have arisen to develop bone substitutes that potentially mimic native bone tissue structure and function. Large tissue replacements have failed in the past due to the slow penetration of the host vasculature, leading to necrosis at the central region of the engineered tissues. For this reason, multiple microscale strategies have been developed to induce and incorporate vascular networks within engineered bone constructs before implantation in order to achieve successful integration with the host tissue. Previous attempts to engineer vascularized bone tissue only focused on the effect of a single component among the three main components of TE (scaffold, cells, or signaling cues) and have only achieved limited success. However, with efforts to improve the engineered bone tissue substitutes, bone TE approaches have become more complex by combining multiple strategies simultaneously. The driving force behind combining various TE strategies is to produce bone replacements that more closely recapitulate human physiology. Here, we review and discuss the limitations of current bone TE approaches and possible strategies to improve vascularization in bone tissue substitutes. PMID:22765012

Role of Oxidative Damage in Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

2014-01-01

During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

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.

Extracellular Matrix-mediated Tissue Remodeling Following Axial Movement of Teeth

PubMed Central

Luan, Xianghong; Ito, Yoshihiro; Holliday, Sean; Walker, Cameron; Daniel, Jon; Galang, Therese M.; Fukui, Tadayoshi; Yamane, Akira; Begole, Ellen; Evans, Carla; Diekwisch, Thomas G.H.

2007-01-01

SUMMARY Tooth eruption is a multifactorial process involving movement of existing tissues and formation of new tissues coordinated by a complex set of genetic events. We have used the model of the unopposed rodent molar to study morphological and genetic mechanisms involved in axial movement of teeth. Following extraction of opposing upper molars, lower molars supererupted by 0.13 mm. Labeled tissue sections revealed significant amounts of new bone and cementum apposition at the root apex of the unopposed side following supereruption for 12 days. Newly apposited cementum and alveolar bone layers were approximately 3-fold thicker in the experimental vs the control group, whereas periodontal ligament width was maintained. Tartrate-resistant acid phosphatase staining indicated bone resorption at the mesial alveolar walls of unopposed molars and provided in tandem with new bone formation at the distal alveolar walls an explanation for the distal drift of molars in this model. Microarray analysis and semiquantitative RT-PCR demonstrated a significant increase in collagen I, integrin β5, and SPARC gene expression as revealed by comparison between the unopposed molar group and the control group. Immunohistochemical verification revealed increased levels of integrin β5 and SPARC labeling in the periodontal ligament of the unopposed molar. Together our findings suggest that posteruptive axial movement of teeth was accomplished by significant formation of new root cementum and alveolar bone at the root apex in tandem with upregulation of collagen I, integrin β5, and SPARC gene expression. PMID:17015623

RhBMP-2 loaded 3D-printed mesoporous silica/calcium phosphate cement porous scaffolds with enhanced vascularization and osteogenesis properties

NASA Astrophysics Data System (ADS)

Li, Cuidi; Jiang, Chuan; Deng, Yuan; Li, Tao; Li, Ning; Peng, Mingzheng; Wang, Jinwu

2017-01-01

A major limitation in the development of effective scaffolds for bone regeneration has been the limited vascularization of the regenerating tissue. Here, we propose the development of a novel calcium phosphate cement (CPC)-based scaffold combining the properties of mesoporous silica (MS) with recombinant human bone morphogenic protein-2 (rhBMP-2) to facilitate vascularization and osteogenesis. Specifically, the development of a custom MS/CPC paste allowed the three-dimensional (3D) printing of scaffolds with a defined macroporous structure and optimized silicon (Si) ions release profile to promote the ingrowth of vascular tissue at an early stage after implantation in support of tissue viability and osteogenesis. In addition, the scaffold microstructure allowed the prolonged release of rhBMP-2, which in turn significantly stimulated the osteogenesis of human bone marrow stromal cells in vitro and of bone regeneration in vivo as shown in a rabbit femur defect repair model. Thus, the combination MS/CPC/rhBMP-2 scaffolds might provide a solution to issues of tissue necrosis during the regeneration process and therefore might be able to be readily developed into a useful tool for bone repair in the clinic.

In vivo bone regeneration using a novel porous bioactive composite

NASA Astrophysics Data System (ADS)

Xie, En; Hu, Yunyu; Chen, Xiaofeng; Bai, Xuedong; Li, Dan; Ren, Li; Zhang, Ziru

2008-11-01

Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

Wound healing of osteotomy defects prepared with piezo or conventional surgical instruments: a pilot study in rabbits.

PubMed

Ma, Li; Mattheos, Nikos; Sun, Yan; Liu, Xi Ling; Yip Chui, Ying; Lang, Niklaus Peter

2015-08-01

The aim of the present study was to evaluate and compare the wound-healing process following osteotomies performed with either conventional rotary burs or piezoelectric surgery in a rabbit model. Two types of osteotomy window defects of the nasal cavities were prepared on the nasal bone of 16 adult New Zealand white rabbits with either a conventional rotary bur or piezo surgery. The defects were covered with a resorbable membrane. Four animals were killed at 1, 2, 3, and 5 weeks after the surgical procedure, respectively. Histological and morphometric evaluations were performed to assess the volumetric density of various tissue components: the blood clot, vascularized structures, provisional matrix, osteoid, mineralized bone, bone debris, residual tissue, and old bone. Significantly more bone debris was found at 1 week in the conventionally-prepared defects compared to the piezo surgically-prepared defects. At 2 and 3 weeks, a newly-formed hard tissue bridge, mainly composed of woven bone, was seen; however, no statistically-significant differences were observed. At 5 weeks, the defects were completely filled with newly-formed bone. The defects prepared by piezo surgery showed a significantly decreased proportion of bone debris at 1 week, compared to conventional rotary bur defect. © 2014 Wiley Publishing Asia Pty Ltd.

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering.

PubMed

Doğan, Ayşegül; Demirci, Selami; Bayir, Yasin; Halici, Zekai; Karakus, Emre; Aydin, Ali; Cadirci, Elif; Albayrak, Abdulmecit; Demirci, Elif; Karaman, Adem; Ayan, Arif Kursat; Gundogdu, Cemal; Sahin, Fikrettin

2014-11-01

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

Towards a cell-based mechanostat theory of bone: the need to account for osteocyte desensitisation and osteocyte replacement.

PubMed

Lerebours, Chloé; Buenzli, Pascal R

2016-09-06

Bone׳s mechanostat theory describes the adaptation of bone tissues to their mechanical environment. Many experiments have investigated and observed such structural adaptation. However, there is still much uncertainty about how to define the reference mechanical state at which bone structure is adapted and stable. Clinical and experimental observations show that this reference state varies both in space and in time, over a wide range of timescales. We propose here an osteocyte-based mechanostat theory that encodes the mechanical reference state in osteocyte properties. This theory assumes that osteocytes are initially formed adapted to their current local mechanical environment through modulation of their properties. We distinguish two main types of physiological processes by which osteocytes subsequently modify the reference mechanical state at different timescales. One is cell desensitisation, which occurs rapidly and reversibly during an osteocyte׳s lifetime. The other is the replacement of osteocytes during bone remodelling, which occurs over the long timescales of bone turnover. The novelty of this theory is to propose that long-lasting morphological and genotypic osteocyte properties provide a material basis for a long-term mechanical memory of bone that is gradually reset by bone remodelling. We test this theory by simulating long-term mechanical disuse (modelling spinal cord injury), and short-term mechanical loadings (modelling daily exercises) with a mathematical model. The consideration of osteocyte desensitisation and of osteocyte replacement by remodelling is able to capture a number of phenomena and timescales observed during the mechanical adaptation of bone tissues, lending support to this theory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adenovirus-mediated transfer of hepatocyte growth factor gene to human dental pulp stem cells under good manufacturing practice improves their potential for periodontal regeneration in swine.

PubMed

Cao, Yu; Liu, Zhenhai; Xie, Yilin; Hu, Jingchao; Wang, Hua; Fan, Zhipeng; Zhang, Chunmei; Wang, Jingsong; Wu, Chu-Tse; Wang, Songlin

2015-12-15

Periodontitis is one of the most widespread infectious diseases in humans. We previously promoted significant periodontal tissue regeneration in swine models with the transplantation of autologous periodontal ligament stem cells (PDLSCs) and PDLSC sheet. We also promoted periodontal tissue regeneration in a rat model with a local injection of allogeneic bone marrow mesenchymal stem cells. The purpose of the present study is to investigate the roles of the hepatocyte growth factor (HGF) and human dental pulp stem cells (DPSCs) in periodontal tissue regeneration in swine. In the present study, we transferred an adenovirus that carried HGF gene into human DPSCs (HGF-hDPSCs) under good manufacturing practice (GMP) conditions. These cells were then transplanted into a swine model for periodontal regeneration. Twenty miniature pigs were used to generate periodontitis with bone defect of 5 mm in width, 7 mm in length, and 3 mm in depth. After 12 weeks, clinical, radiological, quantitative and histological assessment of regenerated periodontal tissues was performed to compare periodontal regeneration in swine treated with cell implantation. Our study showed that injecting HGF-hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. A hDPSC or HGF-hDPSC sheet showed superior periodontal tissue regeneration compared to the injection of dissociated cells. However, the sheets required surgical placement; thus, they were suitable for surgically-managed periodontitis treatments. The adenovirus-mediated transfer of the HGF gene markedly decreased hDPSC apoptosis in a hypoxic environment or in serum-free medium, and it increased blood vessel regeneration. This study indicated that HGF-hDPSCs produced under GMP conditions significantly improved periodontal bone regeneration in swine; thus, this method represents a potential clinical application for periodontal regeneration.

Periodontal tissue regeneration by combined implantation of adipose tissue-derived stem cells and platelet-rich plasma in a canine model.

PubMed

Tobita, Morikuni; Uysal, Cagri A; Guo, Xin; Hyakusoku, Hiko; Mizuno, Hiroshi

2013-12-01

One goal of periodontal therapy is to regenerate periodontal tissues. Stem cells, growth factors and scaffolds and biomaterials are vital for the restoration of the architecture and function of complex tissues. Adipose tissue-derived stem cells (ASCs) are an ideal population of stem cells for practical regenerative medicine. In addition, platelet-rich plasma (PRP) can be useful for its ability to stimulate tissue regeneration. PRP contains various growth factors and may be useful as a cell carrier in stem cell therapies. The purpose of this study was to determine whether a mixture of ASCs and PRP promoted periodontal tissue regeneration in a canine model. Autologous ASCs and PRP were implanted into areas with periodontal tissue defects. Periodontal tissue defects that received PRP alone or non-implantation were also examined. Histologic, immunohistologic and x-ray studies were performed 1 or 2 months after implantation. The amount of newly formed bone and the scale of newly formed cementum in the region of the periodontal tissue defect were analyzed on tissue sections. The areas of newly formed bone and cementum were greater 2 months after implantation of ASCs and PRP than at 1 month after implantation, and the radiopacity in the region of the periodontal tissue defect increased markedly by 2 months after implantation. The ASCs and PRP group exhibited periodontal tissue with the correct architecture, including alveolar bone, cementum-like structures and periodontal ligament-like structures, by 2 months after implantation. These findings suggest that a combination of autologous ASCs and PRP promotes periodontal tissue regeneration that develops the appropriate architecture for this complex tissue. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Y-90 SPECT ML image reconstruction with a new model for tissue-dependent bremsstrahlung production using CT information: a proof-of-concept study

NASA Astrophysics Data System (ADS)

Lim, Hongki; Fessler, Jeffrey A.; Wilderman, Scott J.; Brooks, Allen F.; Dewaraja, Yuni K.

2018-06-01

While the yield of positrons used in Y-90 PET is independent of tissue media, Y-90 SPECT imaging is complicated by the tissue dependence of bremsstrahlung photon generation. The probability of bremsstrahlung production is proportional to the square of the atomic number of the medium. Hence, the same amount of activity in different tissue regions of the body will produce different numbers of bremsstrahlung photons. Existing reconstruction methods disregard this tissue-dependency, potentially impacting both qualitative and quantitative imaging of heterogeneous regions of the body such as bone with marrow cavities. In this proof-of-concept study, we propose a new maximum-likelihood method that incorporates bremsstrahlung generation probabilities into the system matrix, enabling images of the desired Y-90 distribution to be reconstructed instead of the ‘bremsstrahlung distribution’ that is obtained with existing methods. The tissue-dependent probabilities are generated by Monte Carlo simulation while bone volume fractions for each SPECT voxel are obtained from co-registered CT. First, we demonstrate the tissue dependency in a SPECT/CT imaging experiment with Y-90 in bone equivalent solution and water. Visually, the proposed reconstruction approach better matched the true image and the Y-90 PET image than the standard bremsstrahlung reconstruction approach. An XCAT phantom simulation including bone and marrow regions also demonstrated better agreement with the true image using the proposed reconstruction method. Quantitatively, compared with the standard reconstruction, the new method improved estimation of the liquid bone:water activity concentration ratio by 40% in the SPECT measurement and the cortical bone:marrow activity concentration ratio by 58% in the XCAT simulation.

Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.

PubMed

Haze, Amir; Taylor, Angela L; Haegewald, Stefan; Leiser, Yoav; Shay, Boaz; Rosenfeld, Eli; Gruenbaum-Cohen, Yael; Dafni, Leah; Zimmermann, Bernd; Heikinheimo, Kristiina; Gibson, Carolyn W; Fisher, Larry W; Young, Marian F; Blumenfeld, Anat; Bernimoulin, Jean P; Deutsch, Dan

2009-06-01

Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these many EMPs induces the regeneration and what mechanisms are involved. Here we show that a single recombinant human amelogenin protein (rHAM(+)), induced in vivo regeneration of all tooth-supporting tissues after creation of experimental periodontitis in a dog model. To further understand the regeneration process, amelogenin expression was detected in normal and regenerating cells of the alveolar bone (osteocytes, osteoblasts and osteoclasts), periodontal ligament, cementum and in bone marrow stromal cells. Amelogenin expression was highest in areas of high bone turnover and activity. Further studies showed that during the first 2 weeks after application, rHAM(+) induced, directly or indirectly, significant recruitment of mesenchymal progenitor cells, which later differentiated to form the regenerated periodontal tissues. The ability of a single protein to bring about regeneration of all periodontal tissues, in the correct spatio-temporal order, through recruitment of mesenchymal progenitor cells, could pave the way for development of new therapeutic devices for treatment of periodontal, bone and ligament diseases based on rHAM(+).

Contrast Agents for Micro-Computed Tomography of Microdamage in Bone

DTIC Science & Technology

2011-01-01

solution from DI water (or PBS). For the second model, a 5 mm cube of cortical bone tissue was embedded in polymethylmethacrylate and sectioned...radiography1 and as a radiopacifer in polymethylmethacrylate bone cement.2 Current commercial products for either application use microscale BaSO4 particles... polymethylmethacrylate bone cement (Lewis, 1997). The objective of this study was to non-destructively and three-dimensionally image microdamage

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

NASA Technical Reports Server (NTRS)

Schreurs, Ann-Sofie; Torres, S.; Truong, T.; Moyer, E. L.; Kumar, A.; Tahimic, Candice C. G.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

2016-01-01

Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the cancellous tibia. Treatment caused bone loss in wildtype mice, as expected. Treatment also caused deficits in microarchitecture of mCAT mice, although less severe than wildtype mice in some parameters (percent bone volume, structural model index and cortical area). In conclusion, our results indicate that endogenous ROS signaling in both osteoblast and osteoclast lineage cells contributes to skeletal growth and remodeling, and quenching oxidative damage could play a role in bone loss prevention.

A TPMS-based method for modeling porous scaffolds for bionic bone tissue engineering.

PubMed

Shi, Jianping; Zhu, Liya; Li, Lan; Li, Zongan; Yang, Jiquan; Wang, Xingsong

2018-05-09

In the field of bone defect repair, gradient porous scaffolds have received increased attention because they provide a better environment for promoting tissue regeneration. In this study, we propose an effective method to generate bionic porous scaffolds based on the TPMS (triply periodic minimal surface) and SF (sigmoid function) methods. First, cortical bone morphological features (e.g., pore size and distribution) were determined for several regions of a rabbit femoral bone by analyzing CT-scans. A finite element method was used to evaluate the mechanical properties of the bone at these respective areas. These results were used to place different TPMS substructures into one scaffold domain with smooth transitions. The geometrical parameters of the scaffolds were optimized to match the elastic properties of a human bone. With this proposed method, a functional gradient porous scaffold could be designed and produced by an additive manufacturing method.

Nanoindentation measurements of biomechanical properties in mature and newly formed bone tissue surrounding an implant.

PubMed

Vayron, Romain; Barthel, Etienne; Mathieu, Vincent; Soffer, Emmanuel; Anagnostou, Fani; Haiat, Guillaume

2012-02-01

The characterization of the biomechanical properties of newly formed bone tissue around implants is important to understand the osseointegration process. The objective of this study is to investigate the evolution of the hardness and indentation modulus of newly formed bone tissue as a function of healing time. To do so, a nanoindentation device is employed following a multimodality approach using histological analysis. Coin-shaped implants were placed in vivo at a distance of 200 μm from the cortical bone surface, leading to an initially empty cavity of 200 μm * 4.4 mm. Three New Zealand White rabbits were sacrificed after 4, 7, and 13 weeks of healing time. The bone samples were embedded and analyzed using histological analyses, allowing to distinguish mature and newly formed bone tissue. The bone mechanical properties were then measured in mature and newly formed bone tissue. The results are within the range of hardness and apparent Young's modulus values reported in previous literature. One-way ANOVA test revealed a significant effect of healing time on the indentation modulus (p < 0.001, F = 111.24) and hardness (p < 0.02, F = 3.47) of bone tissue. A Tukey-Kramer analysis revealed that the biomechanical properties of newly formed bone tissue (4 weeks) were significantly different from those of mature bone tissue. The comparison with the results obtained in Mathieu et al. (2011, "Micro-Brillouin Scattering Measurements in Mature and Newly Formed Bone Tissue Surrounding an Implant," J. Biomech. Eng., 133, 021006). shows that bone mass density increases by approximately 13.5% between newly formed bone (7 weeks) and mature bone tissue.

An image-based skeletal dosimetry model for the ICRP reference adult female—internal electron sources

NASA Astrophysics Data System (ADS)

O'Reilly, Shannon E.; DeWeese, Lindsay S.; Maynard, Matthew R.; Rajon, Didier A.; Wayson, Michael B.; Marshall, Emily L.; Bolch, Wesley E.

2016-12-01

An image-based skeletal dosimetry model for internal electron sources was created for the ICRP-defined reference adult female. Many previous skeletal dosimetry models, which are still employed in commonly used internal dosimetry software, do not properly account for electron escape from trabecular spongiosa, electron cross-fire from cortical bone, and the impact of marrow cellularity on active marrow self-irradiation. Furthermore, these existing models do not employ the current ICRP definition of a 50 µm bone endosteum (or shallow marrow). Each of these limitations was addressed in the present study. Electron transport was completed to determine specific absorbed fractions to both active and shallow marrow of the skeletal regions of the University of Florida reference adult female. The skeletal macrostructure and microstructure were modeled separately. The bone macrostructure was based on the whole-body hybrid computational phantom of the UF series of reference models, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 years-old female cadaver. The active and shallow marrow are typically adopted as surrogate tissue regions for the hematopoietic stem cells and osteoprogenitor cells, respectively. Source tissues included active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume, and cortical bone surfaces. Marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. All other sources were run at the defined ICRP Publication 70 cellularity for each bone site. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or analytically modeled. The method of combining skeletal macrostructure and microstructure absorbed fractions assessed using MCNPX electron transport was found to yield results similar to those determined with the PIRT model applied to the UF adult male skeletal dosimetry model. Calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) but did not follow results from skeletal models based upon assumptions of an infinite expanse of trabecular spongiosa.

Ectopic Osteoid and Bone Formation by Three Calcium-Phosphate Ceramics in Rats, Rabbits and Dogs

PubMed Central

Wang, Liao; Zhang, Bi; Bao, Chongyun; Habibovic, Pamela; Hu, Jing; Zhang, Xingdong

2014-01-01

Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA) sintered at 1200°C and two biphasic calcium phosphate (BCP) ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (β-Tricalcium phosphate), sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model. PMID:25229501

SU-F-T-369: Validation of Monte-Carlo Beam Model for a Range of Small Fields in Heterogeneous Medium - A Measurement Based Study

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

Karthikeyan, N; Bharathiya University, Coimbatore, Tamilnadu; Ganesh, KM

Purpose: To validate the Monaco montecorlo beam model for a range of small field in the heterogeneous medium. Methods: A in-house phantom with three different medium of Foam, PMMA and derlin resembling the densities of lung, soft tissue, and bone was used for the study. The field sizes of 8, 16, 24, 32 and 48mm were studied for the validation of montecarlo algorithm using 0.01cc volume ionchamber and gafchromic films. The 6MV photon beam from Elekta Beam modulator was used with 100cm SAD setup. The outputs were measured at the depth of 5, 10 and 20mm in every second mediummore » with 3cm buildup of first medium for the interface of lung-bone, lung-soft tissue, soft tissue-bone, bone-lung and soft tissue-lung. Similarly, the 2D dose analysis with gamma criteria of 2%2mm were done at the same depths using gafchromic film. For all the measurements 10.4×10.4cm were taken as reference to which the other field sizes were compared. Monaco TPSv.3.20 was used to calculate the dose distribution for all the simulated measurement setups. Results: The average maximum difference among the field sizes of 8, 16, 24, 32 and 48mm at the depth of 5mm in second medium with the interface of lung-bone, lung-soft tissue, soft tissue-bone, bone-lung and soft tissue-lung were observed as 1.29±0.14%, 0.49±0.16%, 0.87±0.23%, 0.92±0.11%, 1.01±0.19% respectively. The minimum and maximum variation of dose among different materials for the smallest field size of 8mm were observed as 0.23% and 1.67% respectively. The 2D analysis showed the average gamma passing of 98.9±0.5%. The calculated two-tailed P-value were showed insignificance with values of 0.562 and 0.452 for both ionchamber and film measurements. Conclusion: The accuracy of dose calculation for the small fields in Monaco Montecarlo TPS algorithm was validated in different inhomogeneous medium and found the results were well correlated with measurement data.« less

Microcomputed tomographic and histomorphometric analyses of novel titanium mesh membranes for guided bone regeneration: a study in rat calvarial defects.

PubMed

Rakhmatia, Yunia Dwi; Ayukawa, Yasunori; Furuhashi, Akihiro; Koyano, Kiyoshi

2014-01-01

The objective of this study was to evaluate the optimal thickness and porosity of novel titanium mesh membranes to enhance bone augmentation, prevent soft tissue ingrowth, and prevent membrane exposure. Six types of novel titanium meshes with different thicknesses and pore sizes, along with three commercially available membranes, were used to cover surgically created calvarial defects in 6-week-old Sprague-Dawley rats. The animals were killed after 4 or 8 weeks. Microcomputed tomographic analyses were performed to analyze the three-dimensional bone volume and bone mineral density. Soft tissue ingrowth was also evaluated histologically and histomorphometrically. The novel titanium membranes used in this study were as effective at augmenting bone in the rat calvarial defect model as the commercially available membranes. The greatest bone volume was observed on 100-μm-thick membranes with larger pores, although these membranes promoted growth of bone with lower mineral density. Soft tissue ingrowth when 100-μm membranes were used was increased at 4 weeks but decreased again by 8 weeks to a level not statistically significantly different from other membranes. Membrane thickness affects the total amount of new bone formation, and membrane porosity is an essential factor for guided bone regeneration, especially during the initial healing period, although the final bone volume obtained is essentially the same. Newly developed titanium mesh membranes of 100 μm in thickness and with large pores appear to be optimal for guided bone regeneration.

[Advances in research and application of beta-tricalcium phosphate, collagen and beta-tricalcium phosphate/collagen composite in bone tissue engineering].

PubMed

Han, Xiang-Yong; Fu, Yuan-Fei; Zhang, Fu-Qiang

2007-02-01

Bone defects in oral and maxillofacial region was a common problem. To repair the defect, bone grafts including autograft, allograft and artificial bone graft were used in clinic despite of their disadvantages. Nowadays, bone tissue engineering has become a commonly used method to repair bone defect. This paper reviewed the application of beta-TCP, collagen and beta-TCP/collagen composite in bone tissue engineering. It was concluded that beta-TCP/collagen composite was a promising materials in bone tissue engineering.

Automatic Fontanel Extraction from Newborns' CT Images Using Variational Level Set

NASA Astrophysics Data System (ADS)

Kazemi, Kamran; Ghadimi, Sona; Lyaghat, Alireza; Tarighati, Alla; Golshaeyan, Narjes; Abrishami-Moghaddam, Hamid; Grebe, Reinhard; Gondary-Jouet, Catherine; Wallois, Fabrice

A realistic head model is needed for source localization methods used for the study of epilepsy in neonates applying Electroencephalographic (EEG) measurements from the scalp. The earliest models consider the head as a series of concentric spheres, each layer corresponding to a different tissue whose conductivity is assumed to be homogeneous. The results of the source reconstruction depend highly on the electric conductivities of the tissues forming the head.The most used model is constituted of three layers (scalp, skull, and intracranial). Most of the major bones of the neonates’ skull are ossified at birth but can slightly move relative to each other. This is due to the sutures, fibrous membranes that at this stage of development connect the already ossified flat bones of the neurocranium. These weak parts of the neurocranium are called fontanels. Thus it is important to enter the exact geometry of fontaneles and flat bone in a source reconstruction because they show pronounced in conductivity. Computer Tomography (CT) imaging provides an excellent tool for non-invasive investigation of the skull which expresses itself in high contrast to all other tissues while the fontanels only can be identified as absence of bone, gaps in the skull formed by flat bone. Therefore, the aim of this paper is to extract the fontanels from CT images applying a variational level set method. We applied the proposed method to CT-images of five different subjects. The automatically extracted fontanels show good agreement with the manually extracted ones.

Fixation of Hydroxyapatite-Coated Revision Implants Is Improved by the Surgical Technique of Cracking the Sclerotic Bone Rim

PubMed Central

Elmengaard, Brian; Bechtold, Joan E.; Chen, Xinqian; Søballe, Kjeld

2013-01-01

Revision joint replacement has poorer outcomes that have been associated with poorer mechanical fixation. We investigate a new bone-sparing surgical technique that locally cracks the sclerotic bone rim formed during aseptic loosening. We inserted 16 hydroxyapatite-coated implants bilaterally in the distal femur of eight dogs, using a controlled weight-bearing experimental model that replicates important features of a typical revision setting. At 8 weeks, a control revision procedure and a crack revision procedure were performed on contralateral implants. The crack procedure used a splined tool to perform a systematic local perforation of the sclerotic bone rim of the revision cavity. After 4 weeks, the hydroxyapatite-coated implants were evaluated for mechanical fixation by a push-out test and for tissue distribution by histomorphometry. The cracking revision procedure resulted in significantly improved mechanical fixation, significantly more bone ongrowth and bone volume in the gap, and reduced fibrous tissue compared to the control revision procedure. The study demonstrates that the sclerotic bone rim prevents bone ingrowth and promotes fixation by fibrous tissue. The effect of the cracking technique may be due to improved access to the vascular compartment of the bone. The cracking technique is a simple surgical method that potentially can improve the fixation of revision implants in sclerotic regions important for obtaining the fixation critical for overall implant stability. PMID:19148940

Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration

PubMed Central

Trachtenberg, Jordan E.; Vo, Tiffany N.; Mikos, Antonios G.

2014-01-01

Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth. PMID:25319726

Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration.

PubMed

Trachtenberg, Jordan E; Vo, Tiffany N; Mikos, Antonios G

2015-03-01

Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth.

Vascularised endosteal bone tissue in armoured sauropod dinosaurs.

PubMed

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-04-26

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature.

Vascularised endosteal bone tissue in armoured sauropod dinosaurs

PubMed Central

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-01-01

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature. PMID:27112710

Effects of multi-deficiencies-diet on bone parameters of peripheral bone in ovariectomized mature rat.

PubMed

El Khassawna, Thaqif; Böcker, Wolfgang; Govindarajan, Parameswari; Schliefke, Nathalie; Hürter, Britta; Kampschulte, Marian; Schlewitz, Gudrun; Alt, Volker; Lips, Katrin Susanne; Faulenbach, Miriam; Möllmann, Henriette; Zahner, Daniel; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Wenisch, Sabine; Langheinrich, Alexander Claus; Schnettler, Reinhard; Heiss, Christian

2013-01-01

Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8) were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs and growth factors in future fracture healing studies.

Effects of Multi-Deficiencies-Diet on Bone Parameters of Peripheral Bone in Ovariectomized Mature Rat

PubMed Central

El Khassawna, Thaqif; Böcker, Wolfgang; Govindarajan, Parameswari; Schliefke, Nathalie; Hürter, Britta; Kampschulte, Marian; Schlewitz, Gudrun; Alt, Volker; Lips, Katrin Susanne; Faulenbach, Miriam; Möllmann, Henriette; Zahner, Daniel; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Wenisch, Sabine; Langheinrich, Alexander Claus; Schnettler, Reinhard; Heiss, Christian

2013-01-01

Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8) were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs and growth factors in future fracture healing studies. PMID:23977109

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.

Histomorphometrical analysis following augmentation of infected extraction sites exhibiting severe bone loss and primarily closed by intrasocket reactive soft tissue.

PubMed

Mardinger, Ofer; Vered, Marilena; Chaushu, Gavriel; Nissan, Joseph

2012-06-01

Intrasocket reactive soft tissue can be used for primary closure during augmentation of infected extraction sites exhibiting severe bone loss prior to implant placement. The present study evaluated the histological characteristics of the initially used intrasocket reactive soft tissue, the overlying soft tissue, and the histomorphometry of the newly formed bone during implant placement. Thirty-six consecutive patients (43 sites) were included in the study. Extraction sites demonstrating extensive bone loss on preoperative periapical and panoramic radiographs served as inclusion criteria. Forty-three implants were inserted after a healing period of 6 months. Porous bovine xenograft bone mineral was used as a single bone substitute. The intrasocket reactive soft tissue was sutured over the grafting material to seal the coronal portion of the socket. Biopsies of the intrasocket reactive soft tissue at augmentation, healed mucosa, and bone cores at implant placement were retrieved and evaluated. The intrasocket reactive soft tissue demonstrated features compatible with granulation tissue and long junctional epithelium. The mucosal samples at implant placement demonstrated histopathological characteristics of keratinized mucosa with no residual elements of granulation tissue. Histomorphometrically, the mean composition of the bone cores was - vital bone 40 ± 19% (13.7-74.8%); bone substitute 25.7 ± 13% (0.6-51%); connective tissue 34.3 ± 15% (13.8-71.9%). Intrasocket reactive soft tissue used for primary closure following ridge augmentation is composed of granulation tissue and long junctional epithelium. At implant placement, clinical and histological results demonstrate its replacement by keratinized gingiva. The histomorphometrical results reveal considerable bone formation. Fresh extraction sites of hopeless teeth demonstrating chronic infection and severe bone loss may be grafted simultaneously with their removal. © 2010 Wiley Periodicals, Inc.

A mathematical multiscale model of bone remodeling, accounting for pore space-specific mechanosensation.

PubMed

Pastrama, Maria-Ioana; Scheiner, Stefan; Pivonka, Peter; Hellmich, Christian

2018-02-01

While bone tissue is a hierarchically organized material, mathematical formulations of bone remodeling are often defined on the level of a millimeter-sized representative volume element (RVE), "smeared" over all types of bone microstructures seen at lower observation scales. Thus, there is no explicit consideration of the fact that the biological cells and biochemical factors driving bone remodeling are actually located in differently sized pore spaces: active osteoblasts and osteoclasts can be found in the vascular pores, whereas the lacunar pores host osteocytes - bone cells originating from former osteoblasts which were then "buried" in newly deposited extracellular bone matrix. We here propose a mathematical description which considers size and shape of the pore spaces where the biological and biochemical events take place. In particular, a previously published systems biology formulation, accounting for biochemical regulatory mechanisms such as the rank-rankl-opg pathway, is cast into a multiscale framework coupled to a poromicromechanical model. The latter gives access to the vascular and lacunar pore pressures arising from macroscopic loading. Extensive experimental data on the biological consequences of this loading strongly suggest that the aforementioned pore pressures, together with the loading frequency, are essential drivers of bone remodeling. The novel approach presented here allows for satisfactory simulation of the evolution of bone tissue under various loading conditions, and for different species; including scenarios such as mechanical dis- and overuse of murine and human bone, or in osteocyte-free bone. Copyright © 2017 Elsevier Inc. All rights reserved.

Minipig model of maxillary distraction osteogenesis: immunohistochemical and histomorphometric analysis of the sequence of osteogenesis.

PubMed

Papadaki, Maria E; Kaban, Leonard B; Troulis, Maria J

2012-11-01

To document the sequence of bone formation in a minipig model of Le Fort I distraction osteogenesis (DO) using immunohistochemistry and histomorphometry. Female Yucatan minipigs (N = 9) in the mixed-dentition stage underwent bilateral maxillary DO. The distraction protocol was 0 days of latency, with a distraction rate of 1 mm/d for 12 days and 24 days of fixation. Specimens were harvested and divided between the central incisors (18 hemi-maxillae) at the end of DO (n = 6), at mid-fixation (n = 6), and at the end of fixation (n = 6). Sections, including the advancement zone, were stained with hematoxylin-eosin, collagen II, CD34, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. Light and fluorescence microscope images (original magnification ×200) were obtained, and percentage of surface area (PSA) of the advancement zone occupied by fibrous tissue, vessels, proliferating cells, osteoid, and bone was determined. An intact maxilla served as the control. At the end of DO, in the advancement zone, the PSA (mean values) of proliferating cells was 33.16%; fibrous tissue, 52%; vessels, 4.35%; and new bone, 5.45%. At the end of fixation, the PSA of proliferating cells decreased to 10.53%, fibrous tissue to 2.3%, and vessels to 1.5% whereas the PSA of new bone increased to 44.9%. The results of this study indicate that the progression of osteogenesis in the maxillary DO wound begins with intense cellular proliferation and vascular fibrous tissue formation and progresses to mature, cancellous bone by the end of fixation. The PSA occupied by mature bone is significantly less than in the control maxilla at the end of fixation. This is consistent with the sequence in the mandibular DO wound. Published by Elsevier Inc.

Amorphous surface layer versus transient amorphous precursor phase in bone - A case study investigated by solid-state NMR spectroscopy.

PubMed

Von Euw, Stanislas; Ajili, Widad; Chan-Chang, Tsou-Hsi-Camille; Delices, Annette; Laurent, Guillaume; Babonneau, Florence; Nassif, Nadine; Azaïs, Thierry

2017-09-01

The presence of an amorphous surface layer that coats a crystalline core has been proposed for many biominerals, including bone mineral. In parallel, transient amorphous precursor phases have been proposed in various biomineralization processes, including bone biomineralization. Here we propose a methodology to investigate the origin of these amorphous environments taking the bone tissue as a key example. This study relies on the investigation of a bone tissue sample and its comparison with synthetic calcium phosphate samples, including a stoichiometric apatite, an amorphous calcium phosphate sample, and two different biomimetic apatites. To reveal if the amorphous environments in bone originate from an amorphous surface layer or a transient amorphous precursor phase, a combined solid-state nuclear magnetic resonance (NMR) experiment has been used. The latter consists of a double cross polarization 1 H→ 31 P→ 1 H pulse sequence followed by a 1 H magnetization exchange pulse sequence. The presence of an amorphous surface layer has been investigated through the study of the biomimetic apatites; while the presence of a transient amorphous precursor phase in the form of amorphous calcium phosphate particles has been mimicked with the help of a physical mixture of stoichiometric apatite and amorphous calcium phosphate. The NMR results show that the amorphous and the crystalline environments detected in our bone tissue sample belong to the same particle. The presence of an amorphous surface layer that coats the apatitic core of bone apatite particles has been unambiguously confirmed, and it is certain that this amorphous surface layer has strong implication on bone tissue biogenesis and regeneration. Questions still persist on the structural organization of bone and biomimetic apatites. The existing model proposes a core/shell structure, with an amorphous surface layer coating a crystalline bulk. The accuracy of this model is still debated because amorphous calcium phosphate (ACP) environments could also arise from a transient amorphous precursor phase of apatite. Here, we provide an NMR spectroscopy methodology to reveal the origin of these ACP environments in bone mineral or in biomimetic apatite. The 1 H magnetization exchange between protons arising from amorphous and crystalline domains shows unambiguously that an ACP layer coats the apatitic crystalline core of bone et biomimetic apatite platelets. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bone Tissue Donation: Tendency and Hurdles.

PubMed

El Hage, S; Dos Santos, M J; de Moraes, E L; de Barros E Silva, L B

2018-03-01

The aim of this study was to identify the percentage of bone tissue donation in a brain death situation and the tendency of donation rate of this tissue in an organ procurement organization in the county of Sao Paulo from 2001 to 2016. It is a retrospective and quantitative study, based on the Organ and Tissue Donation Term of donors who died of brain death between 2001 and 2016. A logistic regression model was applied, and the odds of donation were identified throughout the years, regarding the odds ratio different from zero. Finally, it was measured the accuracy of the odds ratio through the confidence interval. The analysis has shown a significant change on the trend of bone donation (P < .001). In this case, the odds ratio was >1, indicating that the donation rate has increased. However, the percentage of growth is still considered low. The study evidences a growth trend regarding the donation of bone tissue, but the percentage is still too low to adequately meet the demand of patients who need this modality of therapeutic intervention. It is believed that educational campaigns of donation are not emphasizing the donation of tissues for transplantation, which may be directly impacting their consent rates. Copyright © 2018 Elsevier Inc. All rights reserved.

Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo.

PubMed

Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

2016-10-01

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

Canine body composition quantification using 3 tesla fat-water MRI.

PubMed

Gifford, Aliya; Kullberg, Joel; Berglund, Johan; Malmberg, Filip; Coate, Katie C; Williams, Phillip E; Cherrington, Alan D; Avison, Malcolm J; Welch, E Brian

2014-02-01

To test the hypothesis that a whole-body fat-water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi-automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large-breed dogs placed on an obesogenic high-fat, high-fructose diet. Six healthy adult male dogs were scanned twice, at weeks 0 (baseline) and 4, of the dietary regiment. FWMRI-derived volumes of adipose tissue (total, visceral, and subcutaneous), lean tissue, and cortical bone were quantified using a semi-automated approach. Volumes were converted to masses using published tissue densities. FWMRI-derived total mass corresponds with scale mass with a concordance correlation coefficient of 0.931 (95% confidence interval = [0.813, 0.975]), and slope and intercept values of 1.12 and -2.23 kg, respectively. Visceral, subcutaneous and total adipose tissue masses increased significantly from weeks 0 to 4, while neither cortical bone nor lean tissue masses changed significantly. This is evidenced by a mean percent change of 70.2% for visceral, 67.0% for subcutaneous, and 67.1% for total adipose tissue. FWMRI can precisely quantify and map body composition with respect to adipose, lean, and bone tissue depots. The described approach provides a valuable tool to examine the role of distinct tissue depots in an established animal model of human metabolic disease. Copyright © 2013 Wiley Periodicals, Inc.

Shape based segmentation of MRIs of the bones in the knee using phase and intensity information

NASA Astrophysics Data System (ADS)

Fripp, Jurgen; Bourgeat, Pierrick; Crozier, Stuart; Ourselin, Sébastien

2007-03-01

The segmentation of the bones from MR images is useful for performing subsequent segmentation and quantitative measurements of cartilage tissue. In this paper, we present a shape based segmentation scheme for the bones that uses texture features derived from the phase and intensity information in the complex MR image. The phase can provide additional information about the tissue interfaces, but due to the phase unwrapping problem, this information is usually discarded. By using a Gabor filter bank on the complex MR image, texture features (including phase) can be extracted without requiring phase unwrapping. These texture features are then analyzed using a support vector machine classifier to obtain probability tissue matches. The segmentation of the bone is fully automatic and performed using a 3D active shape model based approach driven using gradient and texture information. The 3D active shape model is automatically initialized using a robust affine registration. The approach is validated using a database of 18 FLASH MR images that are manually segmented, with an average segmentation overlap (Dice similarity coefficient) of 0.92 compared to 0.9 obtained using the classifier only.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor.

PubMed

Ball, Owen; Nguyen, Bao-Ngoc B; Placone, Jesse K; Fisher, John P

2016-12-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

PubMed Central

Ball, Owen; Nguyen, Bao-Ngoc B.; Placone, Jesse K.; Fisher, John P.

2016-01-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state. PMID:27272210

Simulating Bone Loss in Microgravity Using Mathematical Formulations of Bone Remodeling

NASA Technical Reports Server (NTRS)

Pennline, James A.

2009-01-01

Most mathematical models of bone remodeling are used to simulate a specific bone disease, by disrupting the steady state or balance in the normal remodeling process, and to simulate a therapeutic strategy. In this work, the ability of a mathematical model of bone remodeling to simulate bone loss as a function of time under the conditions of microgravity is investigated. The model is formed by combining a previously developed set of biochemical, cellular dynamics, and mechanical stimulus equations in the literature with two newly proposed equations; one governing the rate of change of the area of cortical bone tissue in a cross section of a cylindrical section of bone and one governing the rate of change of calcium in the bone fluid. The mechanical stimulus comes from a simple model of stress due to a compressive force on a cylindrical section of bone which can be reduced to zero to mimic the effects of skeletal unloading in microgravity. The complete set of equations formed is a system of first order ordinary differential equations. The results of selected simulations are displayed and discussed. Limitations and deficiencies of the model are also discussed as well as suggestions for further research.

Characterization of bone microstructure using photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Feng, Ting; Kozloff, Kenneth M.; Xu, Guan; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

2015-03-01

Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and deterioration in microarchitecture. This study investigates the feasibility of characterizing bone microstructure by analyzing the frequency spectrum of the photoacoustic signals from the bone. Modeling and numerical simulation of photoacoustic signals and their frequency-domain analysis were performed on trabecular bones with different mineral densities. The resulting quasilinear photoacoustic spectra were fit by linear regression, from which spectral parameter slope can be quantified. The modeling demonstrates that, at an optical wavelength of 685 nm, bone specimens with lower mineral densities have higher slope. Preliminary experiment on osteoporosis rat tibia bones with different mineral contents has also been conducted. The finding from the experiment has a good agreement with the modeling, both demonstrating that the frequency-domain analysis of photoacoustic signals can provide objective assessment of bone microstructure and deterioration. Considering that photoacoustic measurement is non-ionizing, non-invasive, and has sufficient penetration in both calcified and noncalcified tissues, this new technology holds unique potential for clinical translation.

Comparison of mechanical behavior between implant-simulated bone tissue and implant-jaw bone tissue interfaces based on Pull Out testing

NASA Astrophysics Data System (ADS)

Lopez, C.; Muñoz, J. C.; Pinillos, J. C.

2013-11-01

The main purpose of this research was to achieve a better understanding of the relationship within the mechanical properties of human cadaver jaw bone with kind D2 density regarding a substitute polymer to simulate bone tissue, proposed by the ASTM, to evaluate orthopedic implants. However, despite the existence of several densities of foams and his mechanical characterization has been classified into different degrees of tissue densities to simulate cancellous and cortical bone, the value of the densities are different contrasted with the densities of bone tissue, making difficult to establish direct relationship about mechanical behavior between the polymer and the bone material, and therefore no clear criteria known for choosing the polymeric foam which describes the mechanical behavior of tissue for a specific or particular study. To understand such behavior from bone tissue regarding the polymer samples, on this research was a dental implant inserted into the samples, and subjected to destructive Pull Out test according to ASTM F543The Pull Out strength was compared between implant-jawbone and implant-rigid polyurethane foam interfaces. Thus, the test pieces with mechanical behavior similar to bone tissue, enabling an approximation to choose degree appropriate of polymer to replace the bone tissue in future trials biomechanical.

Composite Scaffolds Containing Silk Fibroin, Gelatin, and Hydroxyapatite for Bone Tissue Regeneration and 3D Cell Culturing

PubMed Central

Moisenovich, M. M.; Arkhipova, A. Yu.; Orlova, A. A.; Drutskaya, M. S; Volkova, S. V.; Zacharov, S. E.; Agapov, I. I.; Kirpichnikov, M. P.

2014-01-01

Three-dimensional (3D) silk fibroin scaffolds were modified with one of the major bone tissue derivatives (nano-hydroxyapatite) and/or a collagen derivative (gelatin). Adhesion and proliferation of mouse embryonic fibroblasts (MEF) within the scaffold were increased after modification with either nano-hydroxyapatite or gelatin. However, a significant increase in MEF adhesion and proliferation was observed when both additives were introduced into the scaffold. Such modified composite scaffolds provide a new and better platform to study wound healing, bone and other tissue regeneration, as well as artificial organ bioengineering. This system can further be applied to establish experimental models to study cell-substrate interactions, cell migration and other complex processes, which may be difficult to address using the conventional two-dimensional culture systems. PMID:24772332

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.

Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

PubMed Central

Young, Simon; Kretlow, James D.; Nguyen, Charles; Bashoura, Alex G.; Baggett, L. Scott; Jansen, John A.; Wong, Mark

2008-01-01

Abstract Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs. PMID:18657028

Evaluating differential nuclear DNA yield rates and osteocyte numbers among human bone tissue types: A synchrotron radiation micro-CT approach.

PubMed

Andronowski, Janna M; Mundorff, Amy Z; Pratt, Isaac V; Davoren, Jon M; Cooper, David M L

2017-05-01

Molecular human identification has conventionally focused on DNA sampling from dense, weight-bearing cortical bone tissue, typically from femora or tibiae. A comparison of skeletal elements from three contemporary individuals demonstrated that elements with high quantities of cancellous bone yielded nuclear DNA at the highest rates, suggesting that preferentially sampling cortical bone may be suboptimal (Mundorff & Davoren, 2014). Despite these findings, the reason for the differential DNA yields between cortical and cancellous bone tissues remains unknown. The primary goal of this work is to ascertain whether differences in bone microstructure can be used to explain differential nuclear DNA yield among bone tissue types observed by Mundorff and Davoren (2014), with a focus on osteocytes and the three-dimensional (3D) quantification of their associated lacunae. Osteocytes and other bone cells are recognized to house DNA in bone tissue, thus examining the density of their lacunae may explain why nuclear DNA yield rates differ among bone tissue types. Lacunae were visualized and quantified using synchrotron radiation-based micro-Computed Tomographic imaging (SR micro-CT). Volumes of interest (VOIs) from cortical and cancellous bone tissues (n=129) were comparatively analyzed from the three skeletons sampled for Mundorff and Davoren's (2014) study. Analyses tested the primary hypothesis that the abundance and density of osteocytes (inferred from their lacunar spaces) vary between cortical and cancellous bone tissue types. Results demonstrated that osteocyte lacunar abundance and density vary between cortical and cancellous bone tissue types, with cortical bone VOIs containing a higher lacunar abundance and density. We found that the osteocyte lacunar density values are independent of nuclear DNA yield, suggesting an alternative explanation for the higher nuclear DNA yields from bones with greater quantities of cancellous bone tissue. The use of SR micro-CT allowed for a scale of analysis that revealed a high range of variation in lacunar abundance in both tissue types. Moreover, high-resolution SR micro-CT imaging revealed potential soft tissue remnants within marrow spaces not visible macroscopically. It is hypothesized that soft tissue remnants observed among the trabeculae of skeletal elements with high quantities of cancellous bone tissue are responsible for the high nuclear DNA yields. These findings have significant implications for bone-sample selection for nuclear DNA analysis in a forensic context when skeletal remains are recovered from the ground surface. Copyright © 2017 Elsevier B.V. All rights reserved.

The connection between cellular mechanoregulation and tissue patterns during bone healing.

PubMed

Repp, Felix; Vetter, Andreas; Duda, Georg N; Weinkamer, Richard

2015-09-01

The formation of different tissues in the callus during secondary bone healing is at least partly influenced by mechanical stimuli. We use computer simulations to test the consequences of different hypotheses of the mechanoregulation at the cellular level on the patterns of tissues formed during healing. The computational study is based on an experiment on sheep, where after a tibial osteotomy, histological sections were harvested at different time points. In the simulations, we used a recently proposed basic phenomenological model, which allows ossification to occur either via endochondral or intramembranous ossification, but tries otherwise to employ a minimal number of simulation parameters. The model was extended to consider also the possibility of bone resorption and consequently allowing a description of the full healing progression till the restoration of the cortex. Specifically, we investigated how three changes in the mechanoregulation influence the resulting tissue patterns: (1) a time delay between stimulation of the cell and the formation of the tissue, (2) a variable mechanosensitivity of the cells, and (3) an independence of long time intervals of the soft tissue maturation from the mechanical stimulus. For all three scenarios, our simulations do not show qualitative differences in the time development of the tissue patterns. Largest differences were observed in the intermediate phases of healing in the amount and location of the cartilage. Interestingly, the course of healing was virtually unaltered in case of scenario (3) where tissue maturation proceeded independent of mechanical stimulation.

Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release

DTIC Science & Technology

2011-04-01

tissue and polymer: mineralized tissue stained dark green, osteoid and collagen bright red, soft tissue pink to light green, and erythrocytes bright...of bone, soft tissue , and polymer, high-resolution digital images were acquired at 1.25 · or 20 · . The area of interest comprising the bone defect...bone, soft tissue , and polymer (when present) within the defect were quantified using Metamorph software (Molecular Devices, Inc.) and were calculated

Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress.

PubMed

Shadjou, Nasrin; Hasanzadeh, Mohammad

2015-10-01

Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone. Copyright © 2015 Elsevier B.V. All rights reserved.

Chest wall reconstruction in a canine model using polydioxanone mesh, demineralized bone matrix and bone marrow stromal cells.

PubMed

Tang, Hua; Xu, Zhifei; Qin, Xiong; Wu, Bin; Wu, Lihui; Zhao, XueWei; Li, Yulin

2009-07-01

Extensive chest wall defect reconstruction remains a challenging problem for surgeons. In the past several years, little progress has been made in this area. In this study, a biodegradable polydioxanone (PDO) mesh and demineralized bone matrix (DBM) seeded with osteogenically induced bone marrow stromal cells (BMSCs) were used to reconstruct a 6 cm x 5.5 cm chest wall defect. Four experimental groups were evaluated (n=6 per group): polydioxanone (PDO) mesh/DBMs/BMSCs group, polydioxanone (PDO) mesh/DBMs group, polydioxanone (PDO) mesh group, and a blank group (no materials) in a canine model. All the animals survived except those in the blank group. In all groups receiving biomaterial implants, the polydioxanone (PDO) mesh completely degraded at 24 weeks and was replaced by fibrous tissue with thickness close to that of the normal intercostal tissue (P>0.05). In the polydioxanone (PDO) mesh/DBMs/BMSCs group, new bone formation and bone-union were observed by radiographic and histological examination. More importantly, the reconstructed rib could maintain its original radian and achieve satisfactory biomechanics close to normal ribs in terms of bending stress (P>0.05). However, in the other two groups, fibrous tissue was observed in the defect and junctions, and the reconstructed ribs were easily distorted under an outer force. Based on these results, a surgical approach utilizing biodegradable polydioxanone (PDO) mesh in combination with DBMs and BMSCs could repair the chest wall defect not only in function but also in structure.

Controlled delivery of icariin on small intestine submucosa for bone tissue engineering.

PubMed

Li, Mei; Gu, Qiaoqiao; Chen, Mengjie; Zhang, Chi; Chen, Songdi; Zhao, Jiyuan

2017-02-01

Small intestine submucosa (SIS) has been reported as an excellent biomaterial for tissue engineering because of its naturally occurring collagenous extracellular matrix property with growth factors. However, SIS from submucosal layer of intestine provides different microenvironment from bone tissue, which limits its application to bone regeneration. The object of this study was to improve osteoinductivity of SIS by controlled local delivery of icariin (Ic), a potent osteogenic compound. Sustained release of icariin from SIS scaffold was achieved for >30days and the loading of icariin on SIS scaffold was uniform as scanned by SEM. In vitro experiments revealed that expression of osteogenic differentiation markers (Alp, Bsp and Ocn) was increased after treatment of Ic-SIS scaffold, without significant cytotoxicity. In an in vivo mouse calvarial defect model, bone regeneration was enhanced by SIS implantation at 8weeks, compared to control defect. New bone formation was further improved by implantation with Ic-SIS (low and high) at both 4 and 8weeks. The results of this study suggest that SIS scaffold has the potential as an icariin delivery carrier for enhancement of bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Early healing in alveolar sockets grafted with titanium granules. An experimental study in a dog model.

PubMed

Arruda, Thiago; Sukekava, Flávia; de Souza, André B; Rasmusson, Lars; Araújo, Maurício G

2013-07-01

The aim of the present study was to evaluate the effect of the placement of titanium granules in fresh extraction sockets on early bone formation. The mesial roots of the third maxillary premolars of five adult beagle dogs were removed. On one side of the maxilla (Test group) the fresh extraction socket was grafted with titanium granules, while the contra-lateral socket was left non-grafted (Control group). After 1 month of healing, the dogs were euthanized and biopsies were obtained. The healing tissues were described, and histometric measurements were performed to obtain the percentage area occupied by connective tissue, new mineralized bone, bone marrow, and biomaterial particles. After 1 month of healing the findings from the histological examination revealed the titanium graft to be well incorporated into the provisional connective tissue or newly formed woven bone. The histometric measurements showed, however, that less mineralized bone was formed in the Test group than in the Control group. The present study suggests that the use of titanium granules in fresh extraction sockets was conducive to new bone formation. The graft of titanium granules seems, however, to delay the early phase of the healing process. Copyright © 2012 Wiley Periodicals, Inc.

Quantitative polarized Raman spectroscopy in highly turbid bone tissue

NASA Astrophysics Data System (ADS)

Raghavan, Mekhala; Sahar, Nadder D.; Wilson, Robert H.; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H.; Morris, Michael D.

2010-05-01

Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim/oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim/oim bones (28+/-3 deg) compared to wild-type bones (22+/-3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76+/-2 deg and in oim/oim mice, it is 72+/-4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

Quantitative polarized Raman spectroscopy in highly turbid bone tissue.

PubMed

Raghavan, Mekhala; Sahar, Nadder D; Wilson, Robert H; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H; Morris, Michael D

2010-01-01

Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim/oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim/oim bones (28+/-3 deg) compared to wild-type bones (22+/-3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76+/-2 deg and in oim/oim mice, it is 72+/-4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine

PubMed Central

Sundelacruz, Sarah; Kaplan, David L.

2009-01-01

In osteochondral tissue engineering, cell recruitment, proliferation, differentiation, and patterning are critical for forming biologically and structurally viable constructs for repair of damaged or diseased tissue. However, since constructs prepared ex vivo lack the multitude of cues present in the in vivo microenvironment, cells often need to be supplied with external biological and physical stimuli to coax them towards targeted tissue functions. To determine which stimuli to present to cells, bioengineering strategies can benefit significantly from endogenous examples of skeletogenesis. As an example of developmental skeletogenesis, the developing limb bud serves as an excellent model system in which to study how an osteochondral structures form from undifferentiated precursor cells. Alongside skeletal formation during embryogenesis, bone also possesses innate regenerative capacity, displaying remarkable ability to heal after damage. Bone fracture healing shares many features with bone development, driving the hypothesis that the regenerative process generally recapitulates development. Similarities and differences between the two modes of bone formation may offer insight into the special requirements for healing damaged or diseased bone. Thus, endogenous fracture healing, as an example of regenerative skeletogenesis, may also inform bioengineering strategies. In this review, we summarize the key cellular events involving stem and progenitor cells in developmental and regenerative skeletogenesis, and discuss in parallel the corresponding cell- and scaffold-based strategies that tissue engineers employ to recapitulate these events in vitro. PMID:19508851

Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

NASA Astrophysics Data System (ADS)

Khan, Pintu Kumar; Mahato, Arnab; Kundu, Biswanath; Nandi, Samit K.; Mukherjee, Prasenjit; Datta, Someswar; Sarkar, Soumya; Mukherjee, Jayanta; Nath, Shalini; Balla, Vamsi K.; Mandal, Chitra

2016-09-01

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering.

Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

PubMed Central

Khan, Pintu Kumar; Mahato, Arnab; Kundu, Biswanath; Nandi, Samit K.; Mukherjee, Prasenjit; Datta, Someswar; Sarkar, Soumya; Mukherjee, Jayanta; Nath, Shalini; Balla, Vamsi K.; Mandal, Chitra

2016-01-01

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering. PMID:27604654

The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

PubMed Central

Johnston, Bryan D.; Ward, Wendy E.

2015-01-01

In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed. PMID:26060817

Cone-Beam Computed Tomography Evaluation of Horizontal and Vertical Dimensional Changes in Buccal Peri-Implant Alveolar Bone and Soft Tissue: A 1-Year Prospective Clinical Study.

PubMed

Kaminaka, Akihiro; Nakano, Tamaki; Ono, Shinji; Kato, Tokinori; Yatani, Hirofumi

2015-10-01

This study evaluated changes in the horizontal and vertical dimensions of the buccal alveolar bone and soft tissue over a 1-year period following implant prosthesis. Thirty-three participants with no history of guided bone regeneration or soft tissue augmentation underwent dental implant placement with different types of connections. The dimensions of the buccal alveolar bone and soft tissue were evaluated immediately and at 1 year after prosthesis from reconstructions of cross-sectional cone-beam computed tomography images. The vertical and horizontal loss of buccal bone and soft tissue around implants with conical connections were lower than around those with external or internal connections. Statistically significant negative correlations were observed between initial horizontal bone thickness and changes in vertical bone and soft tissue height (p < .05), and between initial horizontal soft tissue thickness and the change in vertical soft tissue height (p < .05). Implants with a conical connection preserve peri-implant alveolar bone and soft tissue more effectively than other connection types. Furthermore, the initial buccal alveolar bone and soft tissue thickness around the implant platform may influence their vertical dimensional changes at 1 year after implant prosthesis. © 2014 Wiley Periodicals, Inc.

Implantation of Tetrapod-Shaped Granular Artificial Bones or β-Tricalcium Phosphate Granules in a Canine Large Bone-Defect Model

PubMed Central

CHOI, Sungjin; LIU, I-Li; YAMAMOTO, Kenichi; HONNAMI, Muneki; SAKAI, Takamasa; OHBA, Shinsuke; ECHIGO, Ryosuke; SUZUKI, Shigeki; NISHIMURA, Ryouhei; CHUNG, Ung-il; SASAKI, Nobuo; MOCHIZUKI, Manabu

2013-01-01

ABSTRACT We investigated biodegradability and new bone formation after implantation of tetrapod-shaped granular artificial bone (Tetrabone®) or β-tricalcium phosphate granules (β-TCP) in experimental critical-size defects in dogs, which were created through medial and lateral femoral condyles. The defect was packed with Tetrabone® (Tetrabone group) or β-TCP (β-TCP group) or received no implant (control group). Computed tomography (CT) was performed at 0, 4 and 8 weeks after implantation. Micro-CT and histological analysis were conducted to measure the non-osseous tissue rate and the area and distribution of new bone tissue in the defect at 8 weeks after implantation. On CT, β-TCP was gradually resorbed, while Tetrabone® showed minimal resorption at 8 weeks after implantation. On micro-CT, non-osseous tissue rate of the control group was significantly higher compared with the β-TCP and Tetrabone groups (P<0.01), and that of the β-TCP group was significantly higher compared with the Tetrabone group (P<0.05). On histology, area of new bone tissue of the β-TCP group was significantly greater than those of the Tetrabone and control groups (P<0.05), and new bone distribution of the Tetrabone group was significantly greater than those of the β-TCP and control groups (P<0.05). These results indicate differences in biodegradability and connectivity of intergranule pore structure between study samples. In conclusion, Tetrabone® may be superior for the repair of large bone defects in dogs. PMID:24161964

Implantation of tetrapod-shaped granular artificial bones or β-tricalcium phosphate granules in a canine large bone-defect model.

PubMed

Choi, Sungjin; Liu, I-Li; Yamamoto, Kenichi; Honnami, Muneki; Sakai, Takamasa; Ohba, Shinsuke; Echigo, Ryosuke; Suzuki, Shigeki; Nishimura, Ryouhei; Chung, Ung-Il; Sasaki, Nobuo; Mochizuki, Manabu

2014-03-01

We investigated biodegradability and new bone formation after implantation of tetrapod-shaped granular artificial bone (Tetrabone®) or β-tricalcium phosphate granules (β-TCP) in experimental critical-size defects in dogs, which were created through medial and lateral femoral condyles. The defect was packed with Tetrabone® (Tetrabone group) or β-TCP (β-TCP group) or received no implant (control group). Computed tomography (CT) was performed at 0, 4 and 8 weeks after implantation. Micro-CT and histological analysis were conducted to measure the non-osseous tissue rate and the area and distribution of new bone tissue in the defect at 8 weeks after implantation. On CT, β-TCP was gradually resorbed, while Tetrabone® showed minimal resorption at 8 weeks after implantation. On micro-CT, non-osseous tissue rate of the control group was significantly higher compared with the β-TCP and Tetrabone groups (P<0.01), and that of the β-TCP group was significantly higher compared with the Tetrabone group (P<0.05). On histology, area of new bone tissue of the β-TCP group was significantly greater than those of the Tetrabone and control groups (P<0.05), and new bone distribution of the Tetrabone group was significantly greater than those of the β-TCP and control groups (P<0.05). These results indicate differences in biodegradability and connectivity of intergranule pore structure between study samples. In conclusion, Tetrabone® may be superior for the repair of large bone defects in dogs.

Evaluation of bioreactor-cultivated bone by magnetic resonance microscopy and FTIR microspectroscopy.

PubMed

Chesnick, Ingrid E; Avallone, Francis A; Leapman, Richard D; Landis, William J; Eidelman, Naomi; Potter, Kimberlee

2007-04-01

We present a three-dimensional mineralizing model based on a hollow fiber bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the growth and development of the mineralized tissue around the individual fibers were monitored over a period of 9 weeks. Spatial maps of the water proton MRM properties of the intact tissue, with 78 microm resolution, were used to determine changes in tissue composition with development. Unique changes in the mineral and collagen content of the tissue were detected with high specificity by proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At the end of the growth period, the presence of a bone-like tissue was verified by histology and the formation of poorly crystalline apatite was verified by selected area electron diffraction and electron probe X-ray microanalysis. FTIR microspectroscopy confirmed the heterogeneous nature of the bone-like tissue formed. FTIR-derived phosphate maps confirmed that those locations with the lowest PD values contained the most mineral, and FTIR-derived collagen maps confirmed that bright pixels on MTR maps corresponded to regions of high collagen content. In conclusion, the spatial mapping of tissue constituents by FTIR microspectroscopy corroborated the findings of non-invasive MRM measurements and supported the role of MRM in monitoring the bone formation process in vitro.

Evaluation of Bioreactor-Cultivated Bone by Magnetic Resonance Microscopy and FTIR Microspectroscopy

PubMed Central

Chesnick, Ingrid E.; Avallone, Frank; Leapman, Richard D.; Landis, William J.; Eidelman, Naomi; Potter, Kimberlee

2007-01-01

We present a three-dimensional mineralizing model based on a hollow fiber bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the growth and development of the mineralized tissue around the individual fibers were monitored over a period of nine weeks. Spatial maps of the water proton MRM properties of the intact tissue, with 78 μm resolution, were used to determine changes in tissue composition with development. Unique changes in the mineral and collagen content of the tissue were detected with high specificity by proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At the end of the growth period, the presence of a bone-like tissue was verified by histology and the formation of poorly crystalline apatite was verified by selected area electron diffraction and electron probe X-ray microanalysis. FTIR microspectroscopy confirmed the heterogeneous nature of the bone-like tissue formed. FTIR-derived phosphate maps confirmed that those locations with the lowest PD values contained the most mineral, and FTIR-derived collagen maps confirmed that bright pixels on MTR maps corresponded to regions of high collagen content. In conclusion, the spatial mapping of tissue constituents by FTIR microspectroscopy corroborated the findings of non-invasive MRM measurements and supported the role of MRM in monitoring the bone formation process in vitro. PMID:17174620

Graphene and its nanostructure derivatives for use in bone tissue engineering: Recent advances.

PubMed

Shadjou, Nasrin; Hasanzadeh, Mohammad

2016-05-01

Tissue engineering and regenerative medicine represent areas of increasing interest because of the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Graphene and its derivatives have attracted much interest for applications in bone tissue engineering. For this purpose, this review focuses on more recent advances in tissue engineering based on graphene-biomaterials from 2013 to May 2015. The purpose of this article was to give a general description of studies of nanostructured graphene derivatives for bone tissue engineering. In this review, we highlight how graphene family nanomaterials are being exploited for bone tissue engineering. Firstly, the main requirements for bone tissue engineering were discussed. Then, the mechanism by which graphene based materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. In addition, graphene-based bioactive glass, as a potential drug/growth factor carrier, was reviewed which includes the composition-structure-drug delivery relationship and the functional effect on the tissue-stimulation properties. Also, the effect of structural and textural properties of graphene based materials on development of new biomaterials for production of bone implants and bone cements were discussed. Finally, the present review intends to provide the reader an overview of the current state of the graphene based biomaterials in bone tissue engineering, its limitations and hopes as well as the future research trends for this exciting field of science. © 2016 Wiley Periodicals, Inc.

The effects of the concentration of high-density polyethylene particles on the bone-implant interface.

PubMed

Brooks, R A; Sharpe, J R; Wimhurst, J A; Myer, B J; Dawes, E N; Rushton, N

2000-05-01

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10(4), 10(6) or 10(8) high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined. Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05). Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10(8) particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process.

MicroCT-Based Skeletal Models for Use in Tomographic Voxel Phantoms for Radiological Protection

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

Bolch, Wesley

The University of Florida (UF) proposes to develop two high-resolution image-based skeletal dosimetry models for direct use by ICRP Committee 2’s Task Group on Dose Calculation in their forthcoming Reference Voxel Male (RVM) and Reference Voxel Female (RVF) whole-body dosimetry phantoms. These two phantoms are CT-based, and thus do not have the image resolution to delineate and perform radiation transport modeling of the individual marrow cavities and bone trabeculae throughout their skeletal structures. Furthermore, new and innovative 3D microimaging techniques will now be required for the skeletal tissues following Committee 2’s revision of the target tissues of relevance for radiogenicmore » bone cancer induction. This target tissue had been defined in ICRP Publication 30 as a 10-μm cell layer on all bone surfaces of trabecular and cortical bone. The revised target tissue is now a 50-μm layer within the marrow cavities of trabecular bone only and is exclusive of the marrow adipocytes. Clearly, this new definition requires the use of 3D microimages of the trabecular architecture not available from past 2D optical studies of the adult skeleton. With our recent acquisition of two relatively young cadavers (males of age 18-years and 40-years), we will develop a series of reference skeletal models that can be directly applied to (1) the new ICRP reference voxel man and female phantoms developed for the ICRP, and (2) pediatric phantoms developed to target the ICRP reference children. Dosimetry data to be developed will include absorbed fractions for internal beta and alpha-particle sources, as well as photon and neutron fluence-to-dose response functions for direct use in external dosimetry studies of the ICRP reference workers and members of the general public« less

Experimental Determination of the Permeability in the Lacunar-Canalicular Porosity of Bone

PubMed Central

Gailani, Gaffar; Benalla, Mohammed; Mahamud, Rashal; Cowin, Stephen C.; Cardoso, Luis

2010-01-01

Permeability of the mineralized bone tissue is a critical element in understanding fluid flow occurring in the lacunar-canalicular porosity (PLC) compartment of bone and its role in bone nutrition and mechanotransduction. However, the estimation of bone permeability at the tissue level is affected by the influence of the vascular porosity (PV) in macroscopic samples containing several osteons. In this communication, both analytical and experimental approaches are proposed to estimate the lacunar-canalicular permeability in a single osteon. Data from an experimental stress-relaxation test in a single osteon is used to derive the PLC permeability by curve fitting to theoretical results from a compressible transverse isotropic poroelastic model of a porous annular disk under a ramp loading history (Cowin and Mehrabadi 2007; Gailani and Cowin 2008). The PLC tissue intrinsic permeability in the radial direction of the osteon was found to be dependent on the strain rate used and within the range of O(10−24)−O(10−25). The reported values of PLC permeability are in reasonable agreement with previously reported values derived using FEA and nanoindentation approaches. PMID:19831477

Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results.

PubMed

Feitosa, Matheus Levi Tajra; Fadel, Leandro; Beltrão-Braga, Patrícia Cristina Baleeiro; Wenceslau, Cristiane Valverde; Kerkis, Irina; Kerkis, Alexandre; Birgel Júnior, Eduardo Harry; Martins, João Flávio Panattoni; Martins, Daniele dos Santos; Miglino, Maria Angélica; Ambrósio, Carlos Eduardo

2010-10-01

Evaluate the bone tissue recovery following transplantation of ovine mesenchymal stem cells (MSC) from bone marrow and human immature dental-pulp stem cells (hIDPSC) in ovine model of induced osteonecrosis of femoral head (ONFH). Eight sheep were divided in three experimental groups. First group was composed by four animals with ONFH induced by ethanol through central decompression (CD), for control group without any treatment. The second and third group were compose by two animals, six weeks after ONFH induction received transplantation of heterologous ovine MSC (CD + oMSC), and hIDPSC (CD + hIDPSC), respectively. In both experiments the cells were transplanted without application of any type of immunosupression protocol. Our data indicate that both cell types used in experiments were able to proliferate within injured site providing bone tissue recovery. The histological results obtained from CD+hIDPSC suggested that the bone regeneration in such animals was better than that observed in CD animals. Mesenchymal stem cell transplant in induced ovine osteonecrosis of femoral head by central decompression technique is safe, and apparently favors bone regeneration of damaged tissues.

Elastic properties of woven bone: effect of mineral content and collagen fibrils orientation.

PubMed

García-Rodríguez, J; Martínez-Reina, J

2017-02-01

Woven bone is a type of tissue that forms mainly during fracture healing or fetal bone development. Its microstructure can be modeled as a composite with a matrix of mineral (hydroxyapatite) and inclusions of collagen fibrils with a more or less random orientation. In the present study, its elastic properties were estimated as a function of composition (degree of mineralization) and fibril orientation. A self-consistent homogenization scheme considering randomness of inclusions' orientation was used for this purpose. Lacuno-canalicular porosity in the form of periodically distributed void inclusions was also considered. Assuming collagen fibrils to be uniformly oriented in all directions led to an isotropic tissue with a Young's modulus [Formula: see text] GPa, which is of the same order of magnitude as that of woven bone in fracture calluses. By contrast, assuming fibrils to have a preferential orientation resulted in a Young's modulus in the preferential direction of 9-16 GPa depending on the mineral content of the tissue. These results are consistent with experimental evidence for woven bone in foetuses, where collagen fibrils are aligned to a certain extent.

Gene Therapy of Bone Morphogenetic Protein for Periodontal Tissue Engineering

PubMed Central

Jin, Q-M.; Anusaksathien, O.; Webb, S.A.; Rutherford, R.B.; Giannobile, W.V.

2009-01-01

Background The reconstruction of lost periodontal support including bone, ligament, and cementum is a major goal of therapy. Bone morphogenetic proteins (BMPs) have shown much potential in the regeneration of the periodontium. Limitations of BMP administration to periodontal lesions include need for high-dose bolus delivery, BMP transient biological activity, and low bioavailability of factors at the wound site. Gene transfer offers promise as an alternative treatment strategy to deliver BMPs to periodontal tissues. Methods This study utilized ex vivo BMP-7 gene transfer to stimulate tissue engineering of alveolar bone wounds. Syngeneic dermal fibroblasts (SDFs) were transduced ex vivo with adenoviruses encoding either green fluorescent protein (Ad-GFP or control virus), BMP-7 (Ad-BMP-7), or an antagonist of BMP bioactivity, noggin (Ad-noggin). Transduced cells were seeded onto gelatin carriers and then transplanted to large mandibular alveolar bone defects in a rat wound repair model. Results Ad-noggin treatment tended to inhibit osteogenesis as compared to the control-treated and Ad-BMP-7-treated specimens. The osseous lesions treated by Ad-BMP-7 gene delivery demonstrated rapid chrondrogenesis, with subsequent osteogenesis, cementogenesis and predictable bridging of the periodontal bone defects. Conclusion These results demonstrate the first successful evidence of periodontal tissue engineering using ex vivo gene transfer of BMPs and offers a new approach for repairing periodontal defects. PMID:12666709

Numerical Investigation of Shock Wave Propagation in Bone-Like Tissue

NASA Astrophysics Data System (ADS)

Nelms, Matt; Rajendran, Arunachalam

In this investigation, the effects of shock wave propagation in bone-like biomineralized tissue was investigated. The Alligator gar (Atractosteus spatula) exoskeleton is comprised of many disparate scales that provide a biological analog for potential design of flexible protective material systems. The penetration resistant fish scale was modeled by simulating a plate impact test configuration using ABAQUS®finite element (FE) software. The gar scale is identified as a two-phase, (1) hydroxyapatite mineral and (2) collagen protein, biological composite with two distinct layers where a stiff, ceramic-like ganoine overlays a soft, highly ductile bone. The geometry and variation of elastic modulus were determined from high-resolution scanning electron microscopy and dynamic nanoindentation experimentation to develop an idealized computational model for RVE-based FE simulations. The numerical analysis shows the effects of different functional material property variations on the stress histories and energy dissipation generated by wave propagation. Given the constitutive behaviors of the two layers are distinctly different, a brittle tensile damage model was employed to describe the ganoine and Drucker-Prager plasticity was used for the nonlinear response of the bone.

Polyurethane foam scaffold as in vitro model for breast cancer bone metastasis.

PubMed

Angeloni, Valentina; Contessi, Nicola; De Marco, Cinzia; Bertoldi, Serena; Tanzi, Maria Cristina; Daidone, Maria Grazia; Farè, Silvia

2017-11-01

Breast cancer (BC) represents the most incident cancer case in women (29%), with high mortality rate. Bone metastasis occurs in 20-50% cases and, despite advances in BC research, the interactions between tumor cells and the metastatic microenvironment are still poorly understood. In vitro 3D models gained great interest in cancer research, thanks to the reproducibility, the 3D spatial cues and associated low costs, compared to in vivo and 2D in vitro models. In this study, we investigated the suitability of a poly-ether-urethane (PU) foam as 3D in vitro model to study the interactions between BC tumor-initiating cells and the bone microenvironment. PU foam open porosity (>70%) appeared suitable to mimic trabecular bone structure. The PU foam showed good mechanical properties under cyclic compression (E=69-109kPa), even if lower than human trabecular bone. The scaffold supported osteoblast SAOS-2 cell line proliferation, with no cytotoxic effects. Human adipose derived stem cells (ADSC) were cultured and differentiated into osteoblast lineage on the PU foam, as shown by alizarin red staining and RT-PCR, thus offering a bone biomimetic microenvironment to the further co-culture with BC derived tumor-initiating cells (MCFS). Tumor aggregates were observed after three weeks of co-culture by e-cadherin staining and SEM; modification in CaP distribution was identified by SEM-EDX and associated to the presence of tumor cells. In conclusion, we demonstrated the suitability of the PU foam to reproduce a bone biomimetic microenvironment, useful for the co-culture of human osteoblasts/BC tumor-initiating cells and to investigate their interaction. 3D in vitro models represent an outstanding alternative in the study of tumor metastases development, compared to traditional 2D in vitro cultures, which oversimplify the 3D tissue microenvironment, and in vivo studies, affected by low reproducibility and ethical issues. Several scaffold-based 3D in vitro models have been proposed to recapitulate the development of metastases in different body sites but, still, the crucial challenge is to correctly mimic the tissue to be modelled in terms of physical, mechanical and biological properties. Here, we prove the suitability of a porous polyurethane foam, synthesized using an appropriate formulaton, in mimicking the bone tissue microenvironment and in reproducing the metastatic colonization derived from human breast cancer, particularly evidencing the devastating effects on the bone extracellular matrix caused by metastatic spreading. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women

PubMed Central

de Paula, Francisco J. A.; de Araújo, Iana M.; Carvalho, Adriana L.; Elias, Jorge; Salmon, Carlos E. G.; Nogueira-Barbosa, Marcello H.

2015-01-01

Bone marrow harbors a significant amount of body adipose tissue (BMAT). While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism. PMID:26067489

The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women.

PubMed

de Paula, Francisco J A; de Araújo, Iana M; Carvalho, Adriana L; Elias, Jorge; Salmon, Carlos E G; Nogueira-Barbosa, Marcello H

2015-01-01

Bone marrow harbors a significant amount of body adipose tissue (BMAT). While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism.

Cortical bone drilling: An experimental and numerical study.

PubMed

Alam, Khurshid; Bahadur, Issam M; Ahmed, Naseer

2014-12-16

Bone drilling is a common surgical procedure in orthopedics, dental and neurosurgeries. In conventional bone drilling process, the surgeon exerts a considerable amount of pressure to penetrate the drill into the bone tissue. Controlled penetration of drill in the bone is necessary for safe and efficient drilling. Development of a validated Finite Element (FE) model of cortical bone drilling. Drilling experiments were conducted on bovine cortical bone. The FE model of the bone drilling was based on mechanical properties obtained from literature data and additionally conducted microindentation tests on the cortical bone. The magnitude of stress in bone was found to decrease exponentially away from the lips of the drill in simulations. Feed rate was found to be the main influential factor affecting the force and torque in the numerical simulations and experiments. The drilling thrust force and torque were found to be unaffected by the drilling speed in numerical simulations. Simulated forces and torques were compared with experimental results for similar drilling conditions and were found in good agreement.CONCLUSIONS: FE schemes may be successfully applied to model complex kinematics of bone drilling process.

Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model

PubMed Central

Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

2011-01-01

Abstract Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29+, CD44+ and CD166+ after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering. PMID:20636333

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2.

Assessing a relationship between bone microstructure and growth rate: a fluorescent labelling study in the king penguin chick (Aptenodytes patagonicus).

PubMed

de Margerie, E; Robin, J-P; Verrier, D; Cubo, J; Groscolas, R; Castanet, J

2004-02-01

Microstructure-function relationships remain poorly understood in primary bone tissues. The relationship between bone growth rate and bone tissue type, although documented in some species by previous works, remains somewhat unclear and controversial. We assessed this relationship in a species with extreme adaptations, the king penguin (Aptenodytes patagonicus). These birds have a peculiar growth, interrupted 3 months after hatching by the austral winter. Before this interruption, chicks undergo extremely rapid statural and ponderal growth. We recorded experimentally (by means of fluorescent labelling) the growth rate of bone tissue in four long bones (humerus, radius, femur and tibiotarsus) of four king penguin chicks during their fastest phase of growth (3-5 weeks after hatching) and identified the associated bone tissue types ('laminar', 'longitudinal', 'reticular' or 'radial' fibro-lamellar bone tissue). We found the highest bone tissue growth rate known to date, up to 171 microm day(-1) (mean 55 microm day(-1)). There was a highly significant relationship between bone tissue type and growth rate (P<10(-6)). Highest rates were obtained with the radial microarchitecture of fibro-lamellar bone, where cavities in the woven network are aligned radially. This result supports the heuristic value of a relationship between growth rate and bone primary microstructure. However, we also found that growth rates of bone tissue types vary according to the long bone considered (P<10(-5)) (e.g. growth rates were 38% lower in the radius than in the other long bones), a result that puts some restriction on the applicability of absolute growth rate values (e.g. to fossil species). The biomechanical disadvantages of accelerated bone growth are discussed in relation to the locomotor behaviour of the chicks during their first month of life.

Cell culture-based tissue engineering as an alternative to bone grafts in implant dentistry: a literature review.

PubMed

Boeckel, Daniel Gonçalves; Shinkai, Rosemary Sadami Arai; Grossi, Márcio Lima; Teixeira, Eduardo Rolim

2012-09-01

Several biomaterials and techniques for bone grafting have been described in the literature for atresic bone tissue replacement caused by edentulism, surgical resectioning, and traumas. A new technique involves tissue engineering, a promising option to replace bone tissue and solve problems associated with morbidity of autogenous grafting. This literature review aims to describe tissue-engineering techniques using ex vivo cell culture as an alternative to repair bone maxillary atresias and discuss the concepts and potentials of bone regeneration through cell culture techniques as an option for restorative maxillofacial surgery.

Raman spectroscopy of bone metastasis

NASA Astrophysics Data System (ADS)

Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

2012-02-01

Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

Migration and Differentiation of GFP-transplanted Bone Marrow-derived Cells into Experimentally Induced Periodontal Polyp in Mice.

PubMed

Matsuda, Saeka; Shoumura, Masahito; Osuga, Naoto; Tsujigiwa, Hidetsugu; Nakano, Keisuke; Okafuji, Norimasa; Ochiai, Takanaga; Hasegawa, Hiromasa; Kawakami, Toshiyuki

2016-01-01

Perforation of floor of the dental pulp is often encountered during root canal treatment in routine clinical practice of dental caries. If perforation were large, granulation tissue would grow to form periodontal polyp. Granulation tissue consists of proliferating cells however their origin is not clear. It was shown that the cells in granulation tissue are mainly from migration of undifferentiated mesenchymal cells of the bone marrow. Hence, this study utilized GFP bone marrow transplantation mouse model. The floor of the pulp chamber in maxillary first molar was perforated using ½ dental round bur. Morphological assessment was carried out by micro CT and microscopy and GFP cell mechanism was further assessed by immunohistochemistry using double fluorescent staining with GFP-S100A4; GFP-Runx2 and GFP-CD31. Results of micro CT revealed alveolar bone resorption and widening of periodontal ligament. Histopathological examination showed proliferation of fibroblasts with some round cells and blood vessels in the granulation tissue. At 2 weeks, the outermost layer of the granulation tissue was lined by squamous cells with distinct intercellular bridges. At 4 weeks, the granulation tissue became larger than the perforation and the outermost layer was lined by relatively typical stratified squamous epithelium. Double immunofluorescent staining of GFP and Runx2 revealed that both proteins were expressed in spindle-shaped cells. Double immunofluorescent staining of GFP and CD31 revealed that both proteins were expressed in vascular endothelial cells in morphologically distinct vessels. The results suggest that fibroblasts, periodontal ligament fibroblasts and blood vessels in granulation tissue were derived from transplanted-bone marrow cells. Thus, essential growth of granulation tissue in periodontal polyp was caused by the migration of undifferentiated mesenchymal cells derived from bone marrow, which differentiated into fibroblasts and later on differentiated into other cells in response to injury.

Transplantation of mature adipocyte-derived dedifferentiated fat cells into three-wall defects in the rat periodontium induces tissue regeneration.

PubMed

Suzuki, Daigo; Akita, Daisuke; Tsurumachi, Niina; Kano, Koichiro; Yamanaka, Katsuyuki; Kaneko, Tadashi; Kawano, Eisuke; Iguchi, Shinya; Toriumi, Taku; Arai, Yoshinori; Matsumoto, Taro; Sato, Shuichi; Honda, Masaki

2017-01-01

The transplantation of dedifferentiated fat (DFAT) cells in combination with poly(d,l-lactic-co-glycolic acid) (PLGA) scaffolds has previously been proven as an effective approach in promoting periodontal tissue regeneration in a rat fenestration defect model. The aim of this study was to assess the regenerative potential of DFAT cells in a rat model of three-wall periodontal bone defect. Three-wall bone defects were created bilaterally on the mesial side of rat maxillary first molars and were either left untreated or treated by implantation of PLGA scaffolds with DFAT cells or PLGA alone. Four weeks after surgery, the tissues were processed for micro-computed tomography (micro-CT) and histomorphometric examination. Micro-CT revealed that the PLGA/DFAT group had significantly higher rates of bone regeneration than the other groups, while histomorphometric analysis showed that the PLGA/DFAT group had significantly higher densities of collagen fiber bundles in acellular and cellular cementum than the PLGA group. Moreover, the results indicate that the placement of the PLGA scaffold prevented the downgrowth of the junctional epithelium. These findings suggest that DFAT cells contribute to tissue regeneration in three-wall periodontal defects, while PLGA provides space necessary for periodontal tissue restoration.

Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model

PubMed Central

Sieh, Shirly; Lubik, Amy A; Clements, Judith A; Nelson, Colleen C

2010-01-01

Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening. PMID:21197221

Gastrointestinal absorption of americium-241 by orally exposed swine: comparison of experimental results with predictions of metabolic models.

PubMed

Eisele, G R; Bernard, S R; Nestor, C W

1987-10-01

Two groups of 11-week-old swine (40 miniature and 40 domestic swine) received a single oral administration of 1.9 X 10(8) Bq (5.2 mCi) of 241Am citrate, and groups of eight animals, four of each type, were killed and sampled at 1, 2, 4, 8, 16, 24, 48, 72, and 96 h and 30 days later. Uptake and excretion patterns of the radioactivity appeared to occur in three phases: rapid uptake, rapid excretion, and then a slower excretion. All animals were systematically dissected, and the eviscerated carcasses were autoclaved for separation of bone and muscle. The predominant site of deposition was bone, and autoclaving had little effect on releasing 241Am from either bone or muscle. The maximum fractional gastrointestinal absorption of 1.1 X 10(-3) occurred 8 h after radionuclide administration. The tissue distribution data suggest partitions of 50, 20, and 30%, for bone, liver, and other soft tissues, respectively. Two metabolic models were evaluated: a modified Mewhinney-Griffith model and the ICRP 30 model to compare the biological data with model predictions. All models underestimated the actual early time data, but the fits to the experimental results were better at later times.

Computational Evaluation of the Effects of Bone Ingrowth on Bone Resorptive Remodeling after a Cementless Total Hip Arthroplasty

NASA Astrophysics Data System (ADS)

Jung, Duk-Young; Kang, Yu-Bong; Tsutsumi, Sadami; Nakai, Ryusuke; Ikeuchi, Ken; Sekel, Ron

In this study, we simulated a wide cortex separation from a cementless hip prosthesis using the bone resorption remodeling method that is based on the generation of high compressive stress around the distal cortical bone. Thereafter, we estimated the effect on late migration quantities of the hip prosthesis produced by the interface state arising from bone ingrowth. This was accomplished using cortical bone remodeling over a long period of time. Two-dimensional natural hip and implanted hip FEM models were constructed with each of the following interface statements between the bone and prosthesis: (1) non-fixation, (2) proximal 1/3, (3) proximal 2/3 and (4) full-fixation. The fixation interfaces in the fully and partially porous coated regions were rigidly fixed by bony ingrowth. The non-fixation model was constructed as a critical situation, with the fibrous or bony tissue not integrated at all into the implant surface. The daily load history was generated using the three loading cases of a one-legged stance as well as abduction and adduction motions. With the natural hip and one-legged stance, the peak compressive principal stresses were found to be under the criteria value for causing bone resorption, while no implant movement occurred. The migration magnitude of the stem of the proximal 1/3 fixation model with adduction motion was much higher, reaching 6%, 11%and 21%greater than those of the non-fixation, proximal 2/3 fixation and all-fixation models, respectively. The full-fixation model showed the lowest compressive principal stress and implant movement. Thus, we concluded that the late loosening and subsequent movement of the stem in the long term could be estimated with the cortical bone remodeling method based on a high compressive stress at the bone-implant interface. The change caused at the bone-prosthesis interface by bony or fibrous tissue ingrowth constituted the major factor in determining the extent of cortical bone resorption occurring with clinical loosening and subsequent implant movement.

Effect of HIP/Ribosomal Protein L29 Deficiency on Mineral Properties of Murine Bones and Teeth

PubMed Central

Sloofman, Laura G.; Verdelis, Kostas; Spevak, Lyudmila; Zayzafoon, Majd; Yamauchi, Mistuo; Opdenaker, Lynn M.; Farach-Carson, Mary C.; Boskey, Adele L.; Kirn-Safran, Catherine B.

2010-01-01

Mice lacking HIP/RPL29, a component of the ribosomal machinery, display increased bone fragility. To understand the effect of sub-efficient protein synthetic rates on mineralized tissue quality, we performed dynamic and static histomorphometry and examined the mineral properties of both bones and teeth in HIP/RPL29 knock-out mice using Fourier transform infrared imaging (FTIRI). While loss of HIP/RPL29 consistently reduced total bone size, decreased mineral apposition rates were not significant, indicating that short stature is not primarily due to impaired osteoblast function. Interestingly, our microspectroscopic studies showed that a significant decrease in collagen crosslinking during maturation of HIP/RPL29-null bone precedes an overall enhancement in the relative extent of mineralization of both trabecular and cortical adult bones. This report provides strong genetic evidence that ribosomal insufficiency induces subtle organic matrix deficiencies which elevates calcification. Consistent with the HIP/RPL29-null bone phenotype, HIP/RPL29-deficient teeth also showed reduced geometric properties accompanied with relative increased mineral densities of both dentin and enamel. Increased mineralization associated with enhanced tissue fragility related to imperfection in organic phase microstructure evokes defects seen in matrix protein-related bone and tooth diseases. Thus, HIP/RPL29 mice constitute a new genetic model for studying the contribution of global protein synthesis in the establishment of organic and inorganic phases in mineral tissues. PMID:20362701

Application of Additive Manufacturing in Oral and Maxillofacial Surgery.

PubMed

Farré-Guasch, Elisabet; Wolff, Jan; Helder, Marco N; Schulten, Engelbert A J M; Forouzanfar, Tim; Klein-Nulend, Jenneke

2015-12-01

Additive manufacturing is the process of joining materials to create objects from digital 3-dimensional (3D) model data, which is a promising technology in oral and maxillofacial surgery. The management of lost craniofacial tissues owing to congenital abnormalities, trauma, or cancer treatment poses a challenge to oral and maxillofacial surgeons. Many strategies have been proposed for the management of such defects, but autogenous bone grafts remain the gold standard for reconstructive bone surgery. Nevertheless, cell-based treatments using adipose stem cells combined with osteoconductive biomaterials or scaffolds have become a promising alternative to autogenous bone grafts. Such treatment protocols often require customized 3D scaffolds that fulfill functional and esthetic requirements, provide adequate blood supply, and meet the load-bearing requirements of the head. Currently, such customized 3D scaffolds are being manufactured using additive manufacturing technology. In this review, 2 of the current and emerging modalities for reconstruction of oral and maxillofacial bone defects are highlighted and discussed, namely human maxillary sinus floor elevation as a valid model to test bone tissue-engineering approaches enabling the application of 1-step surgical procedures and seeding of Good Manufacturing Practice-level adipose stem cells on computer-aided manufactured scaffolds to reconstruct large bone defects in a 2-step surgical procedure, in which cells are expanded ex vivo and seeded on resorbable scaffolds before implantation. Furthermore, imaging-guided tissue-engineering technologies to predetermine the surgical location and to facilitate the manufacturing of custom-made implants that meet the specific patient's demands are discussed. The potential of tissue-engineered constructs designed for the repair of large oral and maxillofacial bone defects in load-bearing situations in a 1-step surgical procedure combining these 2 innovative approaches is particularly emphasized. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Apatite-coated Silk Fibroin Scaffolds to Healing Mandibular Border Defects in Canines

PubMed Central

Zhao, Jun; Zhang, Zhiyuan; Wang, Shaoyi; Sun, Xiaojuan; Zhang, Xiuli; Chen, Jake; Kaplan, David L.; Jiang, Xinquan

2010-01-01

Tissue engineering has become a new approach for repairing bony defects. Highly porous osteoconductive scaffolds perform the important role for the success of bone regeneration. By biomimetic strategy, apatite-coated porous biomaterial based on silk fibroin scaffolds (SS) might provide an enhanced osteogenic environment for bone-related outcomes. To assess the effects of apatite-coated silk fibroin (mSS) biomaterials for bone healing as a tissue engineered bony scaffold, we explored a tissue engineered bony graft using mSS seeded with osteogenically induced autologous bone marrow stromal cells (bMSCs) to repair inferior mandibular border defects in a canine model. The results were compared with those treated with bMSCs/SS constructs, mSS alone, SS alone, autologous mandibular grafts and untreated blank defects. According to radiographic and histological examination, new bone formation was observed from 4 weeks post-operation, and the defect site was completely repaired after 12 months for the bMSCs/mSS group. In the bMSCs/SS group, new bone formation was observed with more residual silk scaffold remaining at the center of the defect compared with the bMSCs/mSS group. The engineered bone with bMSCs/mSS achieved satisfactory bone mineral densities (BMD) at 12 months post-operation close to those of normal mandible (p>0.05). The quantities of newly formed bone area for the bMSCs/mSS group was higher than the bMSCs/SS group (p<0.01), but no significant differences were found when compared with the autograft group (p>0.05). In contrast, bony defects remained in the center with undegraded silk fibroin scaffold and fibrous connective tissue, and new bone only formed at the periphery in the groups treated with mSS or SS alone. The results suggested apatite-coated silk fibroin scaffolds combined with bMSCs could be successfully used to repair mandibular critical size border defects and the premineralization of these porous silk fibroin protein scaffolds provided an increased osteoconductive environment for bMSCs to regenerate sufficient new bone tissue. PMID:19505603

Computed tomography-based tissue-engineered scaffolds in craniomaxillofacial surgery.

PubMed

Smith, M H; Flanagan, C L; Kemppainen, J M; Sack, J A; Chung, H; Das, S; Hollister, S J; Feinberg, S E

2007-09-01

Tissue engineering provides an alternative modality allowing for decreased morbidity of donor site grafting and decreased rejection of less compatible alloplastic tissues. Using image-based design and computer software, a precisely sized and shaped scaffold for osseous tissue regeneration can be created via selective laser sintering. Polycaprolactone has been used to create a condylar ramus unit (CRU) scaffold for application in temporomandibular joint reconstruction in a Yucatan minipig animal model. Following sacrifice, micro-computed tomography and histology was used to demonstrate the efficacy of this particular scaffold design. A proof-of-concept surgery has demonstrated cartilaginous tissue regeneration along the articulating surface with exuberant osseous tissue formation. Bone volumes and tissue mineral density at both the 1 and 3 month time points demonstrated significant new bone growth interior and exterior to the scaffold. Computationally designed scaffolds can support masticatory function in a large animal model as well as both osseous and cartilage regeneration. Our group is continuing to evaluate multiple implant designs in both young and mature Yucatan minipig animals. 2007 John Wiley & Sons, Ltd.

Sphere-shaped nano-hydroxyapatite/chitosan/gelatin 3D porous scaffolds increase proliferation and osteogenic differentiation of human induced pluripotent stem cells from gingival fibroblasts.

PubMed

Ji, Jun; Tong, Xin; Huang, Xiaofeng; Wang, Tiancong; Lin, Zitong; Cao, Yazhou; Zhang, Junfeng; Dong, Lei; Qin, Haiyan; Hu, Qingang

2015-07-08

Hydroxyapatite (HA) is an important component of human bone and bone tissue engineering scaffolds. A plethora of bone tissue engineering scaffolds have been synthesized so far, including nano-HA/chitosan/gelatin (nHA/CG) scaffolds; and for seeding cells, stem cells, especially induced pluripotent stem cells (iPSCs), have been a promising cell source for bone tissue engineering recently. However, the influence of different HA nano-particle morphologies on the osteogenic differentiation of human iPSCs (hiPSCs) from human gingival fibroblasts (hGFs) is unknown. The purpose of this study was to investigate the osteogenic differentiation of hiPSCs from hGFs seeded on nHA/CG scaffolds with 2 shapes (rod and sphere) of nHA particles. Firstly, hGFs isolated from discarded normal gingival tissues were reprogrammed into hiPSCs. Secondly, hiPSCs were seeded on rod-like nHA/CG (rod-nHA/CG) and sphere-shaped nHA/CG (sphere-nHA/CG) scaffolds respectively and then cell/scaffold complexes were cultured in vitro. Scanning electron microscope, hematoxyline and eosin (HE) staining, Masson's staining, and quantitative real-time polymerase chain reaction techniques were used to examine hiPSC morphology, proliferation, and differentiation on rod-nHA/CG and sphere-nHA/CG scaffolds. Finally, hiPSCs composited with 2 kinds of nHA/CG were transplanted in vivo in a subcutaneous implantation model for 12 weeks; pure scaffolds were also transplanted as a blank control. HE, Masson's, and immunohistochemistry staining were applied to detect new bone regeneration ability. The results showed that sphere-nHA/CG significantly increased hiPSCs from hGF proliferation and osteogenic differentiation in vitro. hiPSCs and sphere-nHA/CG composities generated large bone, whereas hiPSCs and rod-nHA/CG composities produced tiny bone in vivo. Moreover, pure scaffolds without cells almost produced no bone. In conclusion, our work provided a potential innovative bone tissue engineering approach using clinically discarded gingival tissues and sphere-nHA/CG scaffolds.

Long-Duration Spaceflight During the Bion-M1 Spaceflight Experiment Resulted in Significant Bone Loss in the Femoral Head and Alterations in Stem Cell Differentiation Potential in Male Mice

NASA Astrophysics Data System (ADS)

Blaber, Elizabeth; Almeida, Eduardo; Grigoryan, Eleonora; Globus, Ruth

Scientific understanding of the effects of microgravity on mammalian physiology has been limited to short duration spaceflight experiments (10-15 days). As long duration and inter-planetary missions are being initiated, there is a great need to understand the long-term effects of spaceflight on various physiological processes, including stem cell-based tissue regeneration. Bion-M1, for the first time, enabled the possibility of studying the effects of 30-days of microgravity exposure on a mouse model with sufficient sample size to enable statistical analysis. In this experiment, we hypothesized that microgravity negatively impacts stem cell based tissue regeneration, such as bone remodeling and regeneration from hematopoietic and mesenchymal precursors, thereby resulting in tissue degeneration in mice exposed to spaceflight. To test this hypothesis we collected the pelvis and proximal femur from space-flown mice and asynchronous ground controls and analyzed bone and bone marrow using techniques including Microcomputed Tomography (MicroCT), and in-vitro differentiation and differentiating cell motility assays. To determine the effects of 30-days spaceflight on bone tissue mass, we used MicroCT to analyze the trabecular bone of the femoral head and the cortical bone of the femoral neck and mid-shaft. We found that spaceflight caused a 45% decrease in bone volume ratio, a 17% decrease in trabecular thickness, a 25% decrease in trabecular number, and a 17% increase in trabecular spacing of trabecular bone. Furthermore, structural model index and trabecular pattern factor were increased by 32% and 82% respectively indicating that 30-days spaceflight resulted not only in a large loss of trabecular bone but also in a decrease of bone strength indicators. Analysis of the femoral neck cortical bone showed an increase in marrow area and cortical porosity indicating an overall widening of the femoral neck. Interestingly, no significant alterations were found in the cortical bone of the femoral mid-shaft. To determine the regenerative potential of osteoblasts derived from mesenchymal stem cells flown in microgravity we conducted post-flight in-vitro osteoblastogenesis and mineralized nodule formation assays. We found an increase in post-flight differentiation and mineralization of microgravity-flown osteogenic cells, suggesting an accumulation of precursor cells that fail to fully differentiate in space, and then resume vigorous osteogenesis upon reloading at 1g. Overall, these preliminary results indicate that exposure to 30-days spaceflight causes significant trabecular bone loss in the femoral head, a decrease in trabecular bone strength indicators, and compensatory widening of the femoral neck. These results, coupled with diminished regenerative potential of bone marrow stem cells during mechanical unloading in microgravity, have potentially serious implications for bone health and fracture risk during long-duration spaceflight.

Physical Activity and Bone Density in Women

NASA Technical Reports Server (NTRS)

Bowley, Susan M.; Whalen, R. T.

2000-01-01

A mathematical model of bone density regulation as a function of the daily tissue "effective" stress has been derived. Using the model, the influence of daily activity in the form of a daily loading history has been related to bone density of the calcaneus. The theory incorporates a stress exponent m to account for differences in the importance of magnitude and number of load cycles experienced during daily activity. We have derived a parameter from the model, the "Bone Density Index" (BDI). We have developed a method of collecting daily habitual loading histories using an insole force sensor interfaced to a portable digital data logger carried in a fanny pack. Our goal for this study was to determine a stress exponent, m, relating GRFz history to Calcaneal Bone Mineral Density (CBMD).

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

The Use of Patient-Specific Induced Pluripotent Stem Cells (iPSCs) to Identify Osteoclast Defects in Rare Genetic Bone Disorders

PubMed Central

Chen, I-Ping

2014-01-01

More than 500 rare genetic bone disorders have been described, but for many of them only limited treatment options are available. Challenges for studying these bone diseases come from a lack of suitable animal models and unavailability of skeletal tissues for studies. Effectors for skeletal abnormalities of bone disorders may be abnormal bone formation directed by osteoblasts or anomalous bone resorption by osteoclasts, or both. Patient-specific induced pluripotent stem cells (iPSCs) can be generated from somatic cells of various tissue sources and in theory can be differentiated into any desired cell type. However, successful differentiation of hiPSCs into functional bone cells is still a challenge. Our group focuses on the use of human iPSCs (hiPSCs) to identify osteoclast defects in craniometaphyseal dysplasia. In this review, we describe the impact of stem cell technology on research for better treatment of such disorders, the generation of hiPSCs from patients with rare genetic bone disorders and current protocols for differentiating hiPSCs into osteoclasts. PMID:25621177

Load-adaptive bone remodeling simulations reveal osteoporotic microstructural and mechanical changes in whole human vertebrae.

PubMed

Badilatti, Sandro D; Christen, Patrik; Parkinson, Ian; Müller, Ralph

2016-12-08

Osteoporosis is a major medical burden and its impact is expected to increase in our aging society. It is associated with low bone density and microstructural deterioration. Treatments are available, but the critical factor is to define individuals at risk from osteoporotic fractures. Computational simulations investigating not only changes in net bone tissue volume, but also changes in its microstructure where osteoporotic deterioration occur might help to better predict the risk of fractures. In this study, bone remodeling simulations with a mechanical feedback loop were used to predict microstructural changes due to osteoporosis and their impact on bone fragility from 50 to 80 years of age. Starting from homeostatic bone remodeling of a group of seven, mixed sex whole vertebrae, five mechanostat models mimicking different biological alterations associated with osteoporosis were developed, leading to imbalanced bone formation and resorption with a total net loss of bone tissue. A model with reduced bone formation rate and cell sensitivity led to the best match of morphometric indices compared to literature data and was chosen to predict postmenopausal osteoporotic bone loss in the whole group. Thirty years of osteoporotic bone loss were predicted with changes in morphometric indices in agreement with experimental measurements, and only showing major deviations in trabecular number and trabecular separation. In particular, although being optimized to match to the morphometric indices alone, the predicted bone loss revealed realistic changes on the organ level and on biomechanical competence. While the osteoporotic bone was able to maintain the mechanical stability to a great extent, higher fragility towards error loads was found for the osteoporotic bones. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long bone histology of the subterranean rodent Bathyergus suillus (Bathyergidae): ontogenetic pattern of cortical bone thickening.

PubMed

Montoya-Sanhueza, Germán; Chinsamy, Anusuya

2017-02-01

Patterns of bone development in mammals are best known from terrestrial and cursorial groups, but there is a considerable gap in our understanding of how specializations for life underground affect bone growth and development. Likewise, studies of bone microstructure in wild populations are still scarce, and they often include few individuals and tend to be focused on adults. For these reasons, the processes generating bone microstructural variation at intra- and interspecific levels are not fully understood. This study comprehensively examines the bone microstructure of an extant population of Cape dune molerats, Bathyergus suillus (Bathyergidae), the largest subterranean mammal endemic to the Western Cape of South Africa. The aim of this study is to investigate the postnatal bone growth of B. suillus using undecalcified histological sections (n = 197) of the femur, humerus, tibia-fibula, ulna and radius, including males and females belonging to different ontogenetic and reproductive stages (n = 42). Qualitative histological features demonstrate a wide histodiversity with thickening of the cortex mainly resulting from endosteal and periosteal bone depositions, whilst there is scarce endosteal resorption and remodeling throughout ontogeny. This imbalanced bone modeling allows the tissues deposited during ontogeny to remain relatively intact, thus preserving an excellent record of growth. The distribution of the different bone tissues observed in the cortex depends on ontogenetic status, anatomical features (e.g. muscle attachment structures) and location on the bone (e.g. anterior or lateral). The type of bone microstructure and modeling is discussed in relation to digging behavior, reproduction and physiology of this species. This study is the first histological assessment describing the process of cortical thickening in long bones of a fossorial mammal. © 2016 Anatomical Society.

Hematopoiesis in 3 dimensions: human and murine bone marrow architecture visualized by confocal microscopy.

PubMed

Takaku, Tomoiku; Malide, Daniela; Chen, Jichun; Calado, Rodrigo T; Kajigaya, Sachiko; Young, Neal S

2010-10-14

In many animals, blood cell production occurs in the bone marrow. Hematopoiesis is complex, requiring self-renewing and pluripotent stem cells, differentiated progenitor and precursor cells, and supportive stroma, adipose tissue, vascular structures, and extracellular matrix. Although imaging is a vital tool in hematology research, the 3-dimensional architecture of the bone marrow tissue in situ remains largely uncharacterized. The major hindrance to imaging the intact marrow is the surrounding bone structures are almost impossible to cut/image through. We have overcome these obstacles and describe a method whereby whole-mounts of bone marrow tissue were immunostained and imaged in 3 dimensions by confocal fluorescence and reflection microscopy. We have successfully mapped by multicolor immunofluorescence the localization pattern of as many as 4 cell features simultaneously over large tiled views and to depths of approximately 150 μm. Three-dimensional images can be assessed qualitatively and quantitatively to appreciate the distribution of cell types and their interrelationships, with minimal perturbations of the tissue. We demonstrate its application to normal mouse and human marrow, to murine models of marrow failure, and to patients with aplastic anemia, myeloid, and lymphoid cell malignancies. The technique should be generally adaptable for basic laboratory investigation and for clinical diagnosis of hematologic diseases.

Effect of Anti-Sclerostin Therapy and Osteogenesis Imperfecta on Tissue-level Properties in Growing and Adult Mice While Controlling for Tissue Age

PubMed Central

Sinder, Benjamin P.; Lloyd, William R.; Salemi, Joseph D.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.

2016-01-01

Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as Osteogenesis Imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly→Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5 weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2–4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages >3wk) and rapidly growing Brtl/+ (at tissue ages > 4wk) mice compared to WT. At identical tissue ages defined by fluorescent labels adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality. PMID:26769006

Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

PubMed

Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

2016-03-01

Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality. Copyright © 2016 Elsevier Inc. All rights reserved.

Mixed reality temporal bone surgical dissector: mechanical design

PubMed Central

2014-01-01

Objective The Development of a Novel Mixed Reality (MR) Simulation. An evolving training environment emphasizes the importance of simulation. Current haptic temporal bone simulators have difficulty representing realistic contact forces and while 3D printed models convincingly represent vibrational properties of bone, they cannot reproduce soft tissue. This paper introduces a mixed reality model, where the effective elements of both simulations are combined; haptic rendering of soft tissue directly interacts with a printed bone model. This paper addresses one aspect in a series of challenges, specifically the mechanical merger of a haptic device with an otic drill. This further necessitates gravity cancelation of the work assembly gripper mechanism. In this system, the haptic end-effector is replaced by a high-speed drill and the virtual contact forces need to be repositioned to the drill tip from the mid wand. Previous publications detail generation of both the requisite printed and haptic simulations. Method Custom software was developed to reposition the haptic interaction point to the drill tip. A custom fitting, to hold the otic drill, was developed and its weight was offset using the haptic device. The robustness of the system to disturbances and its stable performance during drilling were tested. The experiments were performed on a mixed reality model consisting of two drillable rapid-prototyped layers separated by a free-space. Within the free-space, a linear virtual force model is applied to simulate drill contact with soft tissue. Results Testing illustrated the effectiveness of gravity cancellation. Additionally, the system exhibited excellent performance given random inputs and during the drill’s passage between real and virtual components of the model. No issues with registration at model boundaries were encountered. Conclusion These tests provide a proof of concept for the initial stages in the development of a novel mixed-reality temporal bone simulator. PMID:25927300

Science and animal models of marrow stimulation for cartilage repair.

PubMed

Fortier, Lisa A; Cole, Brian J; McIlwraith, C Wayne

2012-03-01

Microfracture of subchondral bone to enhance cartilage repair is a popular surgical technique used in human and animal patients. Clinical results with resolution or improvement in pain are promising and last on average for 2 to 3 years. Animal studies aimed at understanding microfracture indicate that the repair tissue continues to remodel toward chondrogenesis for at least a year, but longer term results are not available to gain insight into the mechanism of microfracture function or failure over time. Subchondral bone sclerosis and central lesional osteophyte formation following subchondral bone microfracture have been observed in animal models of microfracture, but studies do not provide any insight into the etiology of these pathologies. The continued maturation of microfracture repair tissue over time supports further investigation of microfracture or microfracture-augmented cartilage repair procedures with caution for the investigator and clinician to be observant for conditions that lead to subchondral bone sclerosis or central osteophyte formation, and what affect these boney reactions have on clinical outcome.

Novel bone substitute material in alveolar bone healing following tooth extraction: an experimental study in sheep.

PubMed

Liu, Jinyi; Schmidlin, Patrick R; Philipp, Alexander; Hild, Nora; Tawse-Smith, Andrew; Duncan, Warwick

2016-07-01

Electrospun cotton wool-like nanocomposite (ECWN) is a novel synthetic bone substitute that incorporates amorphous calcium phosphate nanoparticles into a biodegradable synthetic copolymer poly(lactide-co-glycolide). The objectives of this study were to develop a tooth extraction socket model in sheep for bone graft research and to compare ECWN and bovine-derived xenograft (BX) in this model. Sixteen cross-bred female sheep were used. Bilateral mandibular premolars were extracted atraumatically. Second and third premolar sockets were filled (Latin-square allocation) with BX, ECWN or left unfilled. Resorbable collagen membranes were placed over BX and selected ECWN grafted sockets. Eight sheep per time period were sacrificed after 8 and 16 weeks. Resin-embedded undemineralised sections were analysed for descriptive histology and histomorphometric analyses. At 8 weeks, there were with no distinct differences in healing among the different sites. At 16 weeks, osseous healing followed a fine trabecular pattern in ECWN sites. Non-grafted sites showed thick trabeculae separated by large areas of fibrovascular connective tissue. In BX grafted sites, xenograft particles were surrounded by newly formed bone or fibrovascular connective tissue. There were no statistically significant differences in bone formation across the four groups. However, ECWN sites had significantly less residual graft material than BX sites at 16 weeks (P = 0.048). This first description of a tooth extraction socket model in sheep supports the utility of this model for bone graft research. The results of this study suggested that the novel material ECWN did not impede bone ingrowth into sockets and showed evidence of material resorption. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Micro Finite Element models of the vertebral body: Validation of local displacement predictions.

PubMed

Costa, Maria Cristiana; Tozzi, Gianluca; Cristofolini, Luca; Danesi, Valentina; Viceconti, Marco; Dall'Ara, Enrico

2017-01-01

The estimation of local and structural mechanical properties of bones with micro Finite Element (microFE) models based on Micro Computed Tomography images depends on the quality bone geometry is captured, reconstructed and modelled. The aim of this study was to validate microFE models predictions of local displacements for vertebral bodies and to evaluate the effect of the elastic tissue modulus on model's predictions of axial forces. Four porcine thoracic vertebrae were axially compressed in situ, in a step-wise fashion and scanned at approximately 39μm resolution in preloaded and loaded conditions. A global digital volume correlation (DVC) approach was used to compute the full-field displacements. Homogeneous, isotropic and linear elastic microFE models were generated with boundary conditions assigned from the interpolated displacement field measured from the DVC. Measured and predicted local displacements were compared for the cortical and trabecular compartments in the middle of the specimens. Models were run with two different tissue moduli defined from microindentation data (12.0GPa) and a back-calculation procedure (4.6GPa). The predicted sum of axial reaction forces was compared to the experimental values for each specimen. MicroFE models predicted more than 87% of the variation in the displacement measurements (R2 = 0.87-0.99). However, model predictions of axial forces were largely overestimated (80-369%) for a tissue modulus of 12.0GPa, whereas differences in the range 10-80% were found for a back-calculated tissue modulus. The specimen with the lowest density showed a large number of elements strained beyond yield and the highest predictive errors. This study shows that the simplest microFE models can accurately predict quantitatively the local displacements and qualitatively the strain distribution within the vertebral body, independently from the considered bone types.

An update on the Application of Nanotechnology in Bone Tissue Engineering.

PubMed

Griffin, M F; Kalaskar, D M; Seifalian, A; Butler, P E

2016-01-01

Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Future studies to improve the application of nanomaterials for bone tissue engineering are needed.

Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study.

PubMed

Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali

2016-10-01

Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan-gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan-gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan-gelatin scaffolds. Implantation of both the gelatin and chitosan-gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P < 0.05). Combination of the gelatin and chitosan considerably increased structural and functional properties of the healing bones when compared to chitosan scaffold (P < 0.05). However, no significant differences were observed between the gelatin and gelatin-chitosan groups in these regards (P > 0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects.

Local electronic structure and nanolevel hierarchical organization of bone tissue: theory and NEXAFS study

NASA Astrophysics Data System (ADS)

Pavlychev, A. A.; Avrunin, A. S.; Vinogradov, A. S.; Filatova, E. O.; Doctorov, A. A.; Krivosenko, Yu S.; Samoilenko, D. O.; Svirskiy, G. I.; Konashuk, A. S.; Rostov, D. A.

2016-12-01

Theoretical and experimental investigations of native bone are carried out to understand relationships between its hierarchical organization and local electronic and atomic structure of the mineralized phase. The 3D superlattice model of a coplanar assembly of the hydroxyapatite (HAP) nanocrystallites separated by the hydrated nanolayers is introduced to account the interplay of short-, long- and super-range order parameters in bone tissue. The model is applied to (i) predict and rationalize the HAP-to-bone spectral changes in the electronic structure and (ii) describe the mechanisms ensuring the link of the hierarchical organization with the electronic structure of the mineralized phase in bone. To check the predictions the near-edge x-ray absorption fine structure (NEXAFS) at the Ca 2p, P 2p and O 1s thresholds is measured for native bone and compared with NEXAFS for reference compounds. The NEXAFS analysis has demonstrated the essential hierarchy induced HAP-to-bone red shifts of the Ca and P 2p-to-valence transitions. The lowest O 1s excitation line at 532.2 eV in bone is assigned with superposition of core transitions in the hydroxide OH-(H2O) m anions, Ca2+(H2O) n cations, the carboxyl groups inside the collagen and [PO4]2- and [PO4]- anions with unsaturated P-O bonds.

Substitute CT generation from a single ultra short time echo MRI sequence: preliminary study

NASA Astrophysics Data System (ADS)

Ghose, Soumya; Dowling, Jason A.; Rai, Robba; Liney, Gary P.

2017-04-01

In MR guided radiation therapy planning both MR and CT images for a patient are acquired and co-registered to obtain a tissue specific HU map. Generation of the HU map directly from the MRI would eliminate the CT acquisition and may improve radiation therapy planning. In this preliminary study of substitute CT (sCT) generation, two porcine leg phantoms were scanned using a 3D ultrashort echo time (PETRA) sequence and co-registered to corresponding CT images to build tissue specific regression models. The model was created from one co-registered CT-PETRA pair to generate the sCT for the other PETRA image. An expectation maximization based clustering was performed on the co-registered PETRA image to identify the soft tissues, dense bone and air class membership probabilities. A tissue specific non linear regression model was built from one registered CT-PETRA pair dataset to predict the sCT of the second PETRA image in a two-fold cross validation schema. A complete substitute CT is generated in 3 min. The mean absolute HU error for air was 0.3 HU, bone was 95 HU, fat was 30 HU and for muscle it was 10 HU. The mean surface reconstruction error for the bone was 1.3 mm. The PETRA sequence enabled a low mean absolute surface distance for the bone and a low HU error for other classes. The sCT generated from a single PETRA sequence shows promise for the generation of fast sCT for MRI based radiation therapy planning.

Inter-dependent tissue growth and Turing patterning in a model for long bone development

NASA Astrophysics Data System (ADS)

Tanaka, Simon; Iber, Dagmar

2013-10-01

The development of long bones requires a sophisticated spatial organization of cellular signalling, proliferation, and differentiation programs. How such spatial organization emerges on the growing long bone domain is still unresolved. Based on the reported biochemical interactions we developed a regulatory model for the core signalling factors IHH, PTCH1, and PTHrP and included two cell types, proliferating/resting chondrocytes and (pre-)hypertrophic chondrocytes. We show that the reported IHH-PTCH1 interaction gives rise to a Schnakenberg-type Turing kinetics, and that inclusion of PTHrP is important to achieve robust patterning when coupling patterning and tissue dynamics. The model reproduces relevant spatiotemporal gene expression patterns, as well as a number of relevant mutant phenotypes. In summary, we propose that a ligand-receptor based Turing mechanism may control the emergence of patterns during long bone development, with PTHrP as an important mediator to confer patterning robustness when the sensitive Turing system is coupled to the dynamics of a growing and differentiating tissue. We have previously shown that ligand-receptor based Turing mechanisms can also result from BMP-receptor, SHH-receptor, and GDNF-receptor interactions, and that these reproduce the wildtype and mutant patterns during digit formation in limbs and branching morphogenesis in lung and kidneys. Receptor-ligand interactions may thus constitute a general mechanism to generate Turing patterns in nature.

Bone marrow-derived cells homing for self-repair of periodontal tissues: a histological characterization and expression analysis

PubMed Central

Wang, Yan; Zhou, Lili; Li, Chen; Xie, Han; Lu, Yuwang; Wu, Ying; Liu, Hongwei

2015-01-01

Periodontitis, a disease leads to the formation of periodontal defect, can result in tooth loss if left untreated. The therapies to repair/regenerate periodontal tissues have attracted lots of attention these years. Bone marrow-derived cells (BMDCs), a group of cells containing heterogeneous stem/progenitor cells, are capable of homing to injured tissues and participating in tissue repair/regeneration. The amplification of autologous BMDCs’ potential in homing for self-repair/regeneration, therefore, might be considered as an alternative therapy except for traditional cell transplantation. However, the knowledge of the BMDCs’ homing and participation in periodontal repair/regeneration is still known little. For the purpose of directly observing BMDCs’ involvement in periodontal repair, chimeric mouse models were established to make their bone marrow cells reconstituted with cells expressing green enhanced fluorescence protein (EGFP) in this study. One month after bone marrow transplantation, periodontal defects were made on the mesial side of bilateral maxillary first molars in chimeric mice. The green fluorescence protein-positive (GFP+) BMDCS in periodontal defect regions were examined by bioluminescent imaging and immunofluorescence staining. GFP+ BMDCs were found to aggregate in the periodontal defect regions and emerge in newly-formed bones or fibers. Some of them also co-expressed markers of fibroblasts, osteoblasts or vascular endothelial cells. These results indicated that BMDCs might contribute to the formation of new fibers, bones and blood vessels during periodontal repair. In conclusion, we speculated that autologous BMDCs were capable of negotiating into the surgical sites created by periodontal operation and participating in tissue repair. PMID:26722424

Scaffold-based Anti-infection Strategies in Bone Repair

PubMed Central

Johnson, Christopher T.; García, Andrés J.

2014-01-01

Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field. PMID:25476163

Four-point bending protocols to study the effects of dynamic strain in osteoblastic cells in vitro.

PubMed

Galea, Gabriel L; Price, Joanna S

2015-01-01

Strain engendered within bone tissue by mechanical loading of the skeleton is a major influence on the processes of bone modeling and remodeling and so a critical determinant of bone mass and architecture. The cells best placed to respond to strain in bone tissue are the resident osteocytes and osteoblasts. To address the mechanisms of strain-related responses in osteoblast-like cells, our group uses both in vivo and in vitro approaches, including a system of four-point bending of the substrate on which cells are cultured. A range of cell lines can be studied using this system but we routinely compare their responses to those in primary cultures of osteoblast-like cells derived from explants of mouse long bones. These cells show a range of well-characterized responses to physiological levels of strain, including increased proliferation, which in vivo is a feature of the osteogenic response.

Three dimensional mapping of strontium in bone by dual energy K-edge subtraction imaging

NASA Astrophysics Data System (ADS)

Cooper, D. M. L.; Chapman, L. D.; Carter, Y.; Wu, Y.; Panahifar, A.; Britz, H. M.; Bewer, B.; Zhouping, W.; Duke, M. J. M.; Doschak, M.

2012-09-01

The bones of many terrestrial vertebrates, including humans, are continually altered through an internal process of turnover known as remodeling. This process plays a central role in bone adaptation and disease. The uptake of fluorescent tetracyclines within bone mineral is widely exploited as a means of tracking new tissue formation. While investigation of bone microarchitecture has undergone a dimensional shift from 2D to 3D in recent years, we lack a 3D equivalent to fluorescent labeling. In the current study we demonstrate the ability of synchrotron radiation dual energy K-edge subtraction (KES) imaging to map the 3D distribution of elemental strontium within rat vertebral samples. This approach has great potential for ex vivo analysis of preclinical models and human tissue samples. KES also represents a powerful tool for investigating the pharmokinetics of strontium-based drugs recently approved in many countries around the globe for the treatment of osteoporosis.

The use of a cartilage decellularized matrix scaffold for the repair of osteochondral defects: the importance of long-term studies in a large animal model.

PubMed

Vindas Bolaños, R A; Cokelaere, S M; Estrada McDermott, J M; Benders, K E M; Gbureck, U; Plomp, S G M; Weinans, H; Groll, J; van Weeren, P R; Malda, J

2017-03-01

To investigate the effect of decellularized cartilage-derived matrix (CDM) scaffolds, by itself and as a composite scaffold with a calcium phosphate (CaP) base, for the repair of osteochondral defects. It was hypothesized that the chondral defects would heal with fibrocartilaginous tissue and that the composite scaffold would result in better bone formation. After an 8-week pilot experiment in a single horse, scaffolds were implanted in eight healthy horses in osteochondral defects on the medial trochlear ridge of the femur. In one joint a composite CDM-CaP scaffold was implanted (+P), in the contralateral joint a CDM only (-P) scaffold. After euthanasia at 6 months, tissues were analysed by histology, immunohistochemistry, micro-CT, biochemistry and biomechanical evaluation. The 8-week pilot showed encouraging formation of bone and cartilage, but incomplete defect filling. At 6 months, micro-CT and histology showed much more limited filling of the defect, but the CaP component of the +P scaffolds was well integrated with the surrounding bone. The repair tissue was fibrotic with high collagen type I and low type II content and with no differences between the groups. There were also no biochemical differences between the groups and repair tissue was much less stiff than normal tissue (P < 0.0001). The implants failed to produce reasonable repair tissue in this osteochondral defect model, although the CaP base in the -P group integrated well with the recipient bone. The study stresses the importance of long-term in vivo studies to assess the efficacy of cartilage repair techniques. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Femoral Head Bone Loss Following Short and Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Blaber, E. A.; Cheng-Campbell, M.; Almeida, E. A. C.

2016-01-01

Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31% decrease in bone volume ratio, a 14% decrease in trabecular thickness, and a 20% decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1.This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.

Femoral Head Bone Loss Following Short and Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Blaber, Elizabeth A.; Cheng-Campbell, Margareth A.; Almeida, Eduardo A. C.

2016-01-01

Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31 decrease in bone volume ratio, a 14 decrease in trabecular thickness, and a 20 decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1. This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.

Anterior Cruciate Ligament-Derived Stem Cells Transduced With BMP2 Accelerate Graft-Bone Integration After ACL Reconstruction.

PubMed

Kawakami, Yohei; Takayama, Koji; Matsumoto, Tomoyuki; Tang, Ying; Wang, Bing; Mifune, Yutaka; Cummins, James H; Warth, Ryan J; Kuroda, Ryosuke; Kurosaka, Masahiro; Fu, Freddie H; Huard, Johnny

2017-03-01

Strong graft-bone integration is a prerequisite for successful graft remodeling after reconstruction of the anterior cruciate ligament (ACL) using soft tissue grafts. Novel strategies to accelerate soft tissue graft-bone integration are needed to reduce the need for bone-tendon-bone graft harvest, reduce patient convalescence, facilitate rehabilitation, and reduce total recovery time after ACL reconstruction. The application of ACL-derived stem cells with enhanced expression of bone morphogenetic protein 2 (BMP2) onto soft tissue grafts in the form of cell sheets will both accelerate and improve the quality of graft-bone integration after ACL reconstruction in a rat model. Controlled laboratory study. ACL-derived CD34+ cells were isolated from remnant human ACL tissues, virally transduced to express BMP2, and embedded within cell sheets. In a rat model of ACL injury, bilateral single-bundle ACL reconstructions were performed, in which cell sheets were wrapped around tendon autografts before reconstruction. Four groups containing a total of 48 rats (96 knees) were established (n = 12 rats; 24 knees per group): CD34+BMP2 (100%), CD34+BMP2 (25%), CD34+ (untransduced), and a control group containing no cells. Six rats from each group were euthanized 2 and 4 weeks after surgery, and each graft was harvested for immunohistochemical and histological analyses. The remaining 6 rats in each group were euthanized at 4 and 8 weeks to evaluate in situ tensile load to failure in each femur-graft-tibia complex. In vitro, BMP2 transduction promoted the osteogenic differentiation of ACL-derived CD34+ cells while retaining their intrinsic multipotent capabilities. Osteoblast densities were greatest in the BMP2 (100%) and BMP2 (25%) groups. Bone tunnels in the CD34+BMP2 (100%) and CD34+BMP2 (25%) groups had the smallest cross-sectional areas according to micro-computed tomography analyses. Graft-bone integration occurred most rapidly in the CD34+BMP2 (25%) group. Tensile load to failure was significantly greater in the groups containing stem cells at 4 and 8 weeks after surgery. Tensile strength was greatest in the CD34+BMP2 (100%) group at 4 weeks, and in the CD34+BMP2 (25%) group at 8 weeks. ACL-derived CD34+ cells transduced with BMP2 accelerated graft-bone integration after ACL reconstruction using soft tissue autografts in a rat model, as evidenced by improved histological appearance and graft-bone interface biology along with tensile load to failure at each time point up to 8 weeks after surgery. A primary disadvantage of using soft tissue grafts for ACL reconstruction is the prolonged time required for bony ingrowth, which delays the initiation of midsubstance graft remodeling. The lack of consistent correlation between the appearance of a "healed" ACL on postoperative magnetic resonance imaging and readiness to return to sport results in athletes being released to sport before the graft is ready to handle high-intensity loading. Therefore, it is desirable to identify strategies that accelerate graft-bone integration, which would reduce the time to biologic fixation, improve the reliability of biologic fixation, allow for accelerated rehabilitation, and potentially reduce the incidence of early graft pullout and late midsubstance failure.

[Development, physiology, and cell activity of bone].

PubMed

de Baat, P; Heijboer, M P; de Baat, C

2005-07-01

Bones are of crucial importance for the human body, providing skeletal support, serving as a home for the formation of haematopoietic cells, and reservoiring calcium and phosphate. Long bones develop by endochondral ossification. Flat bones develop by intramembranous ossification. Bone tissue contains hydroxyapatite and various extracellular proteins, producing bone matrix. Two biological mechanisms, determining the strength of bone, are modelling and remodelling. Modelling can change bone shape and size through bone formation by osteoblasts at some sites and through bone destruction by osteoclasts at other sites. Remodelling is bone turnover, also performed by osteoclasts and osteoblasts. The processes of modelling and remodelling are induced by mechanical loads, predominantly muscle loads. Osteoblasts develop from mesenchymal stem cells. Many stimulating factors are known to activate the differentiation. Mature osteoblasts synthesize bone matrix and may further differentiate into osteocytes. Osteocytes maintain structural bone integrity and allow bone to adapt to any mechanical and chemical stimulus. Osteoclasts derive from haematopoietic stem cells. A number of transcription and growth factors have been identified essential for osteoclast differentiation and function. Finally, there is a complex interaction between osteoblasts and osteoclasts. Bone destruction starts by attachment of osteoclasts to the bone surface. Following this, osteoclasts undergo specific morphological changes. The process of bone destruction starts by acid dissolution of hydroxyapatite. After that osteoclasts start to destruct the organic matrix.

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

The prospective opportunities offered by magnetic scaffolds for bone tissue engineering: a review

PubMed Central

ORTOLANI, ALESSANDRO; BIANCHI, MICHELE; MOSCA, MASSIMILIANO; CARAVELLI, SILVIO; FUIANO, MARIO; MARCACCI, MAURILIO; RUSSO, ALESSANDRO

2016-01-01

Magnetic scaffolds are becoming increasingly attractive in tissue engineering, due to their ability to enhance bone tissue formation by attracting soluble factors, such as growth factors, hormones and polypeptides, directly to the implantation site, as well as their potential to improve the fixation and stability of the implant. Moreover, there is increasing evidence that the synergistic effects of magnetic scaffolds and magnetic fields can promote bone repair and regeneration. In this manuscript we review the recent innovations in bone tissue engineering that exploit magnetic biomaterials combined with static magnetic fields to enhance bone cell adhesion and proliferation, and thus bone tissue growth. PMID:28217659

Muscle-driven finite element simulation of human foot movements.

PubMed

Spyrou, L A; Aravas, N

2012-01-01

This paper describes a finite element scheme for realistic muscle-driven simulation of human foot movements. The scheme is used to simulate human ankle plantar flexion. A three-dimensional anatomically detailed finite element model of human foot and lower leg is developed and the idea of generating natural foot movement based entirely on the contraction of the plantar flexor muscles is used. The bones, ligaments, articular cartilage, muscles, tendons, as well as the rest soft tissues of human foot and lower leg are included in the model. A realistic three-dimensional continuum constitutive model that describes the biomechanical behaviour of muscles and tendons is used. Both the active and passive properties of muscle tissue are accounted for. The materials for bones and ligaments are considered as homogeneous, isotropic and linearly elastic, whereas the articular cartilage and the rest soft tissues (mainly fat) are defined as hyperelastic materials. The model is used to estimate muscle tissue deformations as well as stresses and strains that develop in the lower leg muscles during plantar flexion of the ankle. Stresses and strains that develop in Achilles tendon during such a movement are also investigated.

Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies For Large Segmental Bone Defects Using The Chronic Caprine Tibial Defect Model

DTIC Science & Technology

2014-10-01

spacer placed at the time of the “Pre-Procedure”. Autogenous Cancellous Bone Graft (ACBG harvested from the sternum at the time of the treatment...will receive more specialized training and orientation to microCT analysis, both on a theoretical and practical level. He will work with raw CT...adjacent to the PMMA) composed of mononuclear cells and exhibited extensive, diffuse fibrous connective tissue.  Performed histology on goat autogenous

Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes.

PubMed

Bahney, Chelsea S; Jacobs, Linsey; Tamai, Robert; Hu, Diane; Luan, Tammy F; Wang, Miqi; Reddy, Sanjay; Park, Michelle; Limburg, Sonja; Kim, Hubert T; Marcucio, Ralph; Kuo, Alfred C

2016-03-01

Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages. We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry. Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo. hOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-β superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach.

Design and properties of 3D scaffolds for bone tissue engineering.

PubMed

Gómez, S; Vlad, M D; López, J; Fernández, E

2016-09-15

In this study, the Voronoi tessellation method has been used to design novel bone like three dimension (3D) porous scaffolds. The Voronoi method has been processed with computer design software to obtain 3D virtual isotropic porous interconnected models, exactly matching the main histomorphometric indices of trabecular bone (trabecular thickness, trabecular separation, trabecular number, bone volume to total volume ratio, bone surface to bone volume ratio, etc.). These bone like models have been further computed for mechanical (elastic modulus) and fluid mass transport (permeability) properties. The results show that the final properties of the scaffolds can be controlled during their microstructure and histomorphometric initial design stage. It is also shown that final properties can be tuned during the design stage to exactly match those of trabecular natural bone. Moreover, identical total porosity models can be designed with quite different specific bone surface area and thus, this specific microstructural feature can be used to favour cell adhesion, migration and, ultimately, new bone apposition (i.e. osteoconduction). Once the virtual models are fully characterized and optimized, these can be easily 3D printed by additive manufacturing and/or stereolitography technologies. The significance of this article goes far beyond the specific objectives on which it is focussed. In fact, it shows, in a guided way, the entire novel process that can be followed to design graded porous implants, whatever its external shape and geometry, but internally tuned to the exact histomorphometric indices needed to match natural human tissues microstructures and, consequently, their mechanical and fluid properties, among others. The significance is even more relevant nowadays thanks to the available new computing and design software that is easily linked to the 3D printing new technologies. It is this transversality, at the frontier of different disciplines, the main characteristic that gives this article a high scientific impact and interest to a broaden audience. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

PubMed

Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

2016-11-01

The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue response near the implant surface in a bone marrow microenvironment, and it also shows great potential in making transgenic animal resource applicable to biomaterial studies, so that the design of novel biomaterials could be better guided.

A review of recent advances in the assessment of bone porosity, permeability, and interstitial fluid flow

PubMed Central

Cardoso, Luis; Fritton, Susannah P.; Gailani, Gaffar; Benalla, Mohammed; Cowin, Stephen C.

2012-01-01

This contribution reviews recent research performed to assess the porosity and permeability of bone tissue with the objective of understanding interstitial fluid movement. Bone tissue mechanotransduction is considered to occur due to the passage of interstitial pore fluid adjacent to dendritic cell structures in the lacunar-canalicular porosity. The movement of interstitial fluid is also necessary for the nutrition of osteocytes. This review will focus on four topics related to improved assessment of bone interstitial fluid flow. First, the advantages and limitations of imaging technologies to visualize bone porosities and architecture at several length scales are summarized. Second, recent efforts to measure the vascular porosity and lacunar-canalicular microarchitecture are discussed. Third, studies associated with the measurement and estimation of the fluid pressure and permeability in the vascular and lacunar-canalicular domains are summarized. Fourth, the development of recent models to represent the interchange of fluids between the bone porosities is described. PMID:23174418

Non-Invasive Investigation of Bone Adaptation in Humans to Mechanical Loading

NASA Technical Reports Server (NTRS)

Whalen, R.

1999-01-01

Experimental studies have identified peak cyclic forces, number of loading cycles, and loading rate as contributors to the regulation of bone metabolism. We have proposed a theoretical model that relates bone density to a mechanical stimulus derived from average daily cumulative peak cyclic 'effective' tissue stresses. In order to develop a non-invasive experimental model to test the theoretical model we need to: (1) monitor daily cumulative loading on a bone, (2) compute the internal stress state(s) resulting from the imposed loading, and (3) image volumetric bone density accurately, precisely, and reproducibly within small contiguous volumes throughout the bone. We have chosen the calcaneus (heel) as an experimental model bone site because it is loaded by ligament, tendon and joint contact forces in equilibrium with daily ground reaction forces that we can measure; it is a peripheral bone site and therefore more easily and accurately imaged with computed tomography; it is composed primarily of cancellous bone; and it is a relevant site for monitoring bone loss and adaptation in astronauts and the general population. This paper presents an overview of our recent advances in the areas of monitoring daily ground reaction forces, biomechanical modeling of the forces on the calcaneus during gait, mathematical modeling of calcaneal bone adaptation in response to cumulative daily activity, accurate and precise imaging of the calcaneus with quantitative computed tomography (QCT), and application to long duration space flight.

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.

Loss of Type I Collagen Telopeptide Lysyl Hydroxylation Causes Musculoskeletal Abnormalities in a Zebrafish Model of Bruck Syndrome.

PubMed

Gistelinck, Charlotte; Witten, Paul Eckhard; Huysseune, Ann; Symoens, Sofie; Malfait, Fransiska; Larionova, Daria; Simoens, Pascal; Dierick, Manuel; Van Hoorebeke, Luc; De Paepe, Anne; Kwon, Ronald Y; Weis, MaryAnn; Eyre, David R; Willaert, Andy; Coucke, Paul J

2016-11-01

Bruck syndrome (BS) is a disorder characterized by joint flexion contractures and skeletal dysplasia that shows strong clinical overlap with the brittle bone disease osteogenesis imperfecta (OI). BS is caused by biallelic mutations in either the FKBP10 or the PLOD2 gene. PLOD2 encodes the lysyl hydroxylase 2 (LH2) enzyme, which is responsible for the hydroxylation of lysine residues in fibrillar collagen telopeptides. This hydroxylation directs crosslinking of collagen fibrils in the extracellular matrix, which is necessary to provide stability and tensile integrity to the collagen fibrils. To further elucidate the function of LH2 in vertebrate skeletal development, we created a zebrafish model harboring a homozygous plod2 nonsense mutation resulting in reduced telopeptide hydroxylation and crosslinking of bone type I collagen. Adult plod2 mutants present with a shortened body axis and severe skeletal abnormalities with evidence of bone fragility and fractures. The vertebral column of plod2 mutants is short and scoliotic with compressed vertebrae that show excessive bone formation at the vertebral end plates, and increased tissue mineral density in the vertebral centra. The muscle fibers of mutant zebrafish have a reduced diameter near the horizontal myoseptum. The endomysium, a layer of connective tissue ensheathing the individual muscle fibers, is enlarged. Transmission electron microscopy of mutant vertebral bone shows type I collagen fibrils that are less organized with loss of the typical plywood-like structure. In conclusion, plod2 mutant zebrafish show molecular and tissue abnormalities in the musculoskeletal system that are concordant with clinical findings in BS patients. Therefore, the plod2 zebrafish mutant is a promising model for the elucidation of the underlying pathogenetic mechanisms leading to BS and the development of novel therapeutic avenues in this syndrome. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Geometry Design Optimization of Functionally Graded Scaffolds for Bone Tissue Engineering: A Mechanobiological Approach

PubMed Central

Boccaccio, Antonio; Uva, Antonio Emmanuele; Fiorentino, Michele; Mori, Giorgio; Monno, Giuseppe

2016-01-01

Functionally Graded Scaffolds (FGSs) are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young’s modulus values. For each combination of these variables, the explicit equation of the porosity distribution law–i.e the law that describes the pore dimensions in function of the spatial coordinates–was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards optimizing geometry of functionally graded scaffolds based on mechanobiological criteria. PMID:26771746

Novel bioactivity of phosvitin in connective tissue and bone organogenesis revealed by live calvarial bone organ culture models.

PubMed

Liu, Jess; Czernick, Drew; Lin, Shih-Chun; Alasmari, Abeer; Serge, Dibart; Salih, Erdjan

2013-09-01

Egg yolk phosvitin is one of the most highly phosphorylated extracellular matrix proteins known in nature with unique physico-chemical properties deemed to be critical during ex-vivo egg embryo development. We have utilized our unique live mouse calvarial bone organ culture models under conditions which dissociates the two bone remodeling stages, viz., resorption by osteoclasts and formation by osteoblasts, to highlight important and to date unknown critical biological functions of egg phosvitin. In our resorption model live bone cultures were grown in the absence of ascorbate and were stimulated by parathyroid hormone (PTH) to undergo rapid osteoclast formation/differentiation with bone resorption. In this resorption model native phosvitin potently inhibited PTH-induced osteoclastic bone resorption with simultaneous new osteoid/bone formation in the absence of ascorbate (vitamin C). These surprising and critical observations were extended using the bone formation model in the absence of ascorbate and in the presence of phosvitin which supported the above results. The results were corroborated by analyses for calcium release or uptake, tartrate-resistant acid phosphatase activity (marker for osteoclasts), alkaline phosphatase activity (marker for osteoblasts), collagen and hydroxyproline composition, and histological and quantitative histomorphometric evaluations. The data revealed that the discovered bioactivity of phosvitin mirrors that of ascorbate during collagen synthesis and the formation of new osteoid/bone. Complementing those studies use of the synthetic collagen peptide analog and cultured calvarial osteoblasts in conjunction with mass spectrometric analysis provided results that augmented the bone organ culture work and confirmed the capacity of phosvitin to stimulate differentiation of osteoblasts, collagen synthesis, hydroxyproline formation, and biomineralization. There are striking implications and interrelationships of this affect that relates to the evolutionary inactivation of the gene of an enzyme L-gulono-γ-lactone oxidase, which is involved in the final step of ascorbate biosynthesis, in many vertebrate species including passeriform birds, reptiles and teleost fish whose egg yolk contain phosvitin. These represent examples of how developing ex-vivo embryos of such species can achieve connective tissue and skeletal system formation in the absence of ascorbate. Copyright © 2013 Elsevier Inc. All rights reserved.

New bone formation in a bone defect associated to dental implant using absorbable or non-absorbable membrane in a dog model

PubMed Central

Lopez, Maria de Almeida; Olate, Sergio; Lanata-Flores, Antonio; Pozzer, Leandro; Cavalieri-Pereira, Lucas; Cantín, Mario; Vásquez, Bélgica; de Albergaria-Barbosa, José

2013-01-01

The aim of this research was to determine the bone formation capacity in fenestration defects associated with dental implants using absorbable and non-absorbable membranes. Six dogs were used in the study. In both tibias of each animal 3 implants were installed, and around these 5 mm circular defects were created. The defects were covered with absorbable membranes (experimental group 1), non-absorbable membranes (experimental group 2), and the third defect was not covered (control group). At 3 and 8 weeks post-surgery, the animals were euthanized and the membranes with the bone tissue around the implants were processed for histological analysis. The statistical analysis was conducted with Tukey’s test, considering statistical significance when p<0.1. Adequate bone repair was observed in the membrane-covered defects. At 3 weeks, organization of the tissue, bone formation from the periphery of the defect and the absence of inflammatory infiltrate were observed in both experimental groups, but the defect covered with absorbable membrane presented statistically greater bone formation. At 8 weeks, both membrane-covered defects showed adequate bone formation without significant differences, although they did in fact present differences with the control defect in both periods (p>0.1). In the defects without membrane, continuous connective tissue invasions and bone repair deficiency were observed. There were no significant differences in the characteristics and volume of the neoformed bone in the defects around the implants covered by the different membranes, whereas the control defects produced significantly less bone. The use of biological membranes contributes to bone formation in three-wall defects. PMID:24228090

[Mechanical strength and mechano-compatibility of tissue-engineered bones].

PubMed

Tanaka, Shigeo

2016-01-01

Current artificial bones made of metals and ceramics may be replaced around a decade after implantation due to its low durability, which is brought on by a large difference from the host bone in mechanical properties, i.e., low mechano-compatibility. On the other hand, tissue engineering could be a solution with regeneration of bone tissues from stem cells in vitro. However, there are still some problems to realize exactly the same mechanical properties as those of real bone. This paper introduces the technical background of bone tissue engineering and discusses possible methods for installation of mechano-compatibility into a regenerative bone. At the end, future directions toward the realization of ideal mechano-compatible regenerative bone are proposed.

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

PubMed Central

Chung, Choon G.; James, Aaron W.; Asatrian, Greg; Chang, Le; Nguyen, Alan; Le, Khoi; Bayani, Georgina; Lee, Robert; Stoker, David; Zhang, Xinli

2014-01-01

Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair. PMID:25154782

Carbon Nanostructures in Bone Tissue Engineering

PubMed Central

Perkins, Brian Lee; Naderi, Naghmeh

2016-01-01

Background: Recent advances in developing biocompatible materials for treating bone loss or defects have dramatically changed clinicians’ reconstructive armory. Current clinically available reconstructive options have certain advantages, but also several drawbacks that prevent them from gaining universal acceptance. A wide range of synthetic and natural biomaterials is being used to develop tissue-engineered bone. Many of these materials are currently in the clinical trial stage. Methods: A selective literature review was performed for carbon nanostructure composites in bone tissue engineering. Results: Incorporation of carbon nanostructures significantly improves the mechanical properties of various biomaterials to mimic that of natural bone. Recently, carbon-modified biomaterials for bone tissue engineering have been extensively investigated to potentially revolutionize biomaterials for bone regeneration. Conclusion: This review summarizes the chemical and biophysical properties of carbon nanostructures and discusses their functionality in bone tissue regeneration. PMID:28217212

Spatial relationship between bone formation and mechanical stimulus within cortical bone: Combining 3D fluorochrome mapping and poroelastic finite element modelling.

PubMed

Carrieroa, A; Pereirab, A F; Wilson, A J; Castagno, S; Javaheri, B; Pitsillides, A A; Marenzana, M; Shefelbine, S J

2018-06-01

Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing 'slice and view' 3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average bone formation and peak mechanical stimulus on the tibial endosteal and periosteal surface across the entire cortical surface were created. Results showed that bone formed on the periosteal and endosteal surface in regions of high fluid flow. Peak strain energy density predicted only the formation of bone periosteally. Understanding how the mechanical stimuli spatially relates with regions of cortical bone formation in response to loading will eventually guide loading regime therapies to maintain or restore bone mass in specific sites in skeletal pathologies.

Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

PubMed

Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

2011-11-01

Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

Tissue Engineering Strategies for the Tendon/ligament-to-bone insertion

PubMed Central

Smith, Lester; Xia, Younan; Galatz, Leesa M.; Genin, Guy M.; Thomopoulos, Stavros

2012-01-01

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require re-attachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of re-injury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations. PMID:22185608

Tissue-engineering strategies for the tendon/ligament-to-bone insertion.

PubMed

Smith, Lester; Xia, Younan; Galatz, Leesa M; Genin, Guy M; Thomopoulos, Stavros

2012-01-01

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require reattachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of reinjury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations.

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

PubMed Central

Reumann, Marie K.; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Steven B.; Lukashova, Lyudmila; Boskey, Adele L.; Mayer-Kuckuk, Philipp

2011-01-01

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. PMID:21726677

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

PubMed

Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

2011-10-01

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

Isolation of Precursor Cells from Waste Solid Fat Tissue

NASA Technical Reports Server (NTRS)

Byerly, Diane; Sognier, Marguerite A.

2009-01-01

A process for isolating tissue-specific progenitor cells exploits solid fat tissue obtained as waste from such elective surgical procedures as abdominoplasties (tummy tucks) and breast reductions. Until now, a painful and risky process of aspiration of bone marrow has been used to obtain a limited number of tissue- specific progenitor cells. The present process yields more tissue-specific progenitor cells and involves much less pain and risk for the patient. This process includes separation of fat from skin, mincing of the fat into small pieces, and forcing a fat saline mixture through a sieve. The mixture is then digested with collagenase type I in an incubator. After centrifugation tissue-specific progenitor cells are recovered and placed in a tissue-culture medium in flasks or Petri dishes. The tissue-specific progenitor cells can be used for such purposes as (1) generating three-dimensional tissue equivalent models for studying bone loss and muscle atrophy (among other deficiencies) and, ultimately, (2) generating replacements for tissues lost by the fat donor because of injury or disease.

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism

PubMed Central

Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

2017-01-01

Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor–host cell dynamics, tumor tropism, and hematopoietic cell transplantation. PMID:28484009

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.

PubMed

Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

2017-05-23

Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor-host cell dynamics, tumor tropism, and hematopoietic cell transplantation.

Anabolic actions of PTH (1-34): use of a novel tissue engineering model to investigate temporal effects on bone.

PubMed

Pettway, Glenda J; Schneider, Abraham; Koh, Amy J; Widjaja, Effendi; Morris, Michael D; Meganck, Jeffrey A; Goldstein, Steven A; McCauley, Laurie K

2005-06-01

PTH is in clinical use for the treatment of osteoporosis and is under intensive investigation for its potential in applications of tissue engineering, fracture healing, and implant integration. However, the mechanisms of its action to stimulate bone formation are still unclear. A novel bone tissue engineering model was used to elucidate basic mechanisms of PTH anabolic actions. Ectopic ossicles containing cortical bone, trabecular bone, and a hematopoietic marrow were generated from implanted bone marrow stromal cells (BMSC). One week after implantation, nude mice were administered PTH or vehicle for 1 week (group 1), 3 weeks (group 2), or 7 weeks (group 3). Another group was also treated for 3 weeks, initiated 12 weeks after implantation (group 4). Micro-radiography and histomorphometry revealed increased marrow cellularity in group 1 PTH-treated ossicles, increased bone in group 2 PTH-treated ossicles, and similar amounts of bone in both group 3 and 4 ossicles regardless of treatment. Incidence of phosphate mineral and phosphate mineral to hydroxyproline ratio via Raman spectroscopy were significantly higher after 3 weeks versus 1 week of PTH treatment, but there was no difference between PTH- and vehicle-treated ossicles. Early events of PTH action in group 1 ossicles and the effects of a single injection of PTH on 1- and 2-week-old ossicles were evaluated by Northern blot analysis. Osteocalcin (OC) mRNA was increased after 1 week of intermittent PTH treatment in ossicles and calvaria but an acute injection did not alter OC mRNA. In contrast, a single injection of PTH increased matrix gamma-carboxyglutamic acid protein (MGP) mRNA in 2-week-old ossicles. Differential and temporal-dependent effects of PTH on OC and MGP suggest at the molecular level, that PTH acts to inhibit osteoblast mineralization. However, this does not translate into tissue level alterations. These data indicate that anabolic actions of PTH in ectopic ossicles are temporally dependent on the BMSC implanted and suggest that cell implantation strategies are particularly responsive to PTH.

Whole bone mechanics and bone quality.

PubMed

Cole, Jacqueline H; van der Meulen, Marjolein C H

2011-08-01

The skeleton plays a critical structural role in bearing functional loads, and failure to do so results in fracture. As we evaluate new therapeutics and consider treatments to prevent skeletal fractures, understanding the basic mechanics underlying whole bone testing and the key principles and characteristics contributing to the structural strength of a bone is critical. We therefore asked: (1) How are whole bone mechanical tests performed and what are the key outcomes measured? (2) How do the intrinsic characteristics of bone tissue contribute to the mechanical properties of a whole bone? (3) What are the effects of extrinsic characteristics on whole bone mechanical behavior? (4) Do environmental factors affect whole bone mechanical properties? We conducted a PubMed search using specific search terms and limiting our included articles to those related to in vitro testing of whole bones. Basic solid mechanics concepts are summarized in the context of whole bone testing and the determinants of whole bone behavior. Whole bone mechanical tests measure structural stiffness and strength from load-deformation data. Whole bone stiffness and strength are a function of total bone mass and the tissue geometric distribution and material properties. Age, sex, genetics, diet, and activity contribute to bone structural performance and affect the incidence of skeletal fractures. Understanding and preventing skeletal fractures is clinically important. Laboratory tests of whole bone strength are currently the only measures for in vivo fracture prediction. In the future, combined imaging and engineering models may be able to predict whole bone strength noninvasively.

Postmenopausal Osteoporosis: The Role of Immune System Cells

PubMed Central

Faienza, Maria Felicia; Ventura, Annamaria; Marzano, Flaviana; Cavallo, Luciano

2013-01-01

In the last years, new evidences of the relationship between immune system and bone have been accumulated both in animal models and in humans affected by bone disease, such as rheumatoid arthritis, bone metastasis, periodontitis, and osteoporosis. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue with a subsequent increase in bone fragility and susceptibility to fractures. The combined effects of estrogen deprivation and raising of FSH production occurring in menopause cause a marked stimulation of bone resorption and a rapid bone loss which is central for the onset of postmenopausal osteoporosis. This review focuses on the role of immune system in postmenopausal osteoporosis and on therapeutic strategies targeting osteoimmunology pathways. PMID:23762093

Response Funtions for Computing Absorbed Dose to Skeletal Tissues from Photon Irradiation

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

Eckerman, Keith F; Bolch, W E; Zankl, M

2007-01-01

The calculation of absorbed dose in skeletal tissues at radiogenic risk has been a difficult problem because the relevant structures cannot be represented in conventional geometric terms nor can they be visualised in the tomographic image data used to define the computational models of the human body. The active marrow, the tissue of concern in leukaemia induction, is present within the spongiosa regions of trabecular bone, whereas the osteoprogenitor cells at risk for bone cancer induction are considered to be within the soft tissues adjacent to the mineral surfaces. The International Commission on Radiological Protection (ICRP) recommends averaging the absorbedmore » energy over the active marrow within the spongiosa and over the soft tissues within 10 mm of the mineral surface for leukaemia and bone cancer induction, respectively. In its forthcoming recommendation, it is expected that the latter guidance will be changed to include soft tissues within 50 mm of the mineral surfaces. To address the computational problems, the skeleton of the proposed ICRP reference computational phantom has been subdivided to identify those voxels associated with cortical shell, spongiosa and the medullary cavity of the long bones. It is further proposed that the Monte Carlo calculations with these phantoms compute the energy deposition in the skeletal target tissues as the product of the particle fluence in the skeletal subdivisions and applicable fluence-to-dose response functions. This paper outlines the development of such response functions for photons.« less

Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

PubMed Central

Chiara, Gardin; Letizia, Ferroni; Lorenzo, Favero; Edoardo, Stellini; Diego, Stomaci; Stefano, Sivolella; Eriberto, Bressan; Barbara, Zavan

2012-01-01

Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM) of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs) from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering. PMID:22312283

Wnt and the Wnt signaling pathway in bone development and disease

PubMed Central

Wang, Yiping; Li, Yi-Ping; Paulson, Christie; Shao, Jian-Zhong; Zhang, Xiaoling; Wu, Mengrui; Chen, Wei

2014-01-01

Wnt signaling affects both bone modeling, which occurs during development, and bone remodeling, which is a lifelong process involving tissue renewal. Wnt signals are especially known to affect the differentiation of osteoblasts. In this review, we summarize recent advances in understanding the mechanisms of Wnt signaling, which is divided into two major branches: the canonical pathway and the noncanonical pathway. The canonical pathway is also called the Wnt/β-catenin pathway. There are two major noncanonical pathways: the Wnt-planar cell polarity pathway (Wnt-PCP pathway) and the Wnt-calcium pathway (Wnt-Ca2+ pathway). This review also discusses how Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists affect both the bone modeling and bone remodeling processes. We also review the role of Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists in bone as demonstrated in mouse models. Disrupted Wnt signaling is linked to several bone diseases, including osteoporosis, van Buchem disease, and sclerosteosis. Studying the mechanism of Wnt signaling and its interactions with other signaling pathways in bone will provide potential therapeutic targets to treat these bone diseases. PMID:24389191

Immune and regulatory functions of neutrophils in inflammatory bone loss

PubMed Central

Hajishengallis, George; Moutsopoulos, Niki M.; Hajishengallis, Evlambia; Chavakis, Triantafyllos

2016-01-01

Although historically viewed as merely anti-microbial effectors in acute infection or injury, neutrophils are now appreciated to be functionally versatile with critical roles also in chronic inflammation. Periodontitis, a chronic inflammatory disease that destroys the tooth-supporting gums and bone, is particularly affected by alterations in neutrophil numbers or function, as revealed by observations in monogenic disorders and relevant mouse models. Besides being a significant debilitating disease and health burden in its own right, periodontitis is thus an attractive model to dissect uncharted neutrophil-associated (patho)physiological pathways. Here, we summarize recent evidence that neutrophils can contribute to inflammatory bone loss not only through the typical bystander injury dogma but intriguingly also through their absence from the affected tissue, where they normally perform important immunomodulatory functions. Moreover, we discuss recent advances in the interactions of neutrophils with the vascular endothelium and – upon extravasation – with bacteria, and how the dysregulation of these interactions leads to inflammatory tissue damage. Overall, neutrophils have both protective and destructive roles in periodontitis, as they are involved in both the maintenance of periodontal tissue homeostasis and the induction of inflammatory bone loss. This highlights the importance of developing approaches that promote or sustain a fine balance between homeostatic immunity and inflammatory pathology. PMID:26936034

Feasibility of endoscopic laser speckle imaging modality in the evaluation of auditory disorder: study in bone-tissue phantom

NASA Astrophysics Data System (ADS)

Yu, Sungkon; Jang, Seulki; Lee, Sangyeob; Park, Jihoon; Ha, Myungjin; Radfar, Edalat; Jung, Byungjo

2016-03-01

This study investigates the feasibility of an endoscopic laser speckle imaging modality (ELSIM) in the measurement of perfusion of flowing fluid in optical bone tissue phantom(OBTP). Many studies suggested that the change of cochlear blood flow was correlated with auditory disorder. Cochlear microcirculation occurs under the 200μm thickness bone which is the part of the internal structure of the temporal bone. Concern has been raised regarding of getting correct optical signal from hard tissue. In order to determine the possibility of the measurement of cochlear blood flow under bone tissue using the ELSIM, optical tissue phantom (OTP) mimicking optical properties of temporal bone was applied.

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.

Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment

NASA Astrophysics Data System (ADS)

Lloyd, William R.; Sinder, Benjamin P.; Salemi, Joseph; Ominsky, Michael S.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.

2015-02-01

Osteogenesis imperfecta (OI) is a genetic disorder resulting in defective collagen or collagen-associated proteins and fragile, brittle bones. To date, therapies to improve OI bone mass, such as bisphosphonates, have increased bone mass in the axial skeleton of OI patients, but have shown limited effects at reducing long bone fragility. Sclerostin antibody (Scl- Ab), currently in clinical trials for osteoporosis, stimulates bone formation and may have the potential to reduce long bone fracture rates in OI patients. Scl-Ab has been investigated as an anabolic therapy for OI in the Brtl/+ mouse model of moderately severe Type IV OI. While Scl-Ab increases long bone mass in the Brtl/+ mouse, it is not known whether material properties and composition changes also occur. Here, we report on the effects of Scl-Ab on wild type and Brtl/+ young (3 week) and adult (6 month) male mice. Scl-Ab was administered over 5 weeks (25mg/kg, 2x/week). Raman microspectroscopy and nanoindentation are used for bone composition and biomechanical bone property measurements in excised bone. Fluorescent labels (calcein and alizarin) at 4 time points over the entire treatment period are used to enable measurements at specific tissue age. Differences between wild type and Brtl/+ groups included variations in the mineral and matrix lattices, particularly the phosphate v1, carbonate v1, and the v(CC) proline and hydroxyproline stretch vibrations. Results of Raman spectroscopy corresponded to nanoindentation findings which indicated that old bone (near midcortex) is stiffer (higher elastic modulus) than new bone. We compare and contrast mineral to matrix and carbonate to phosphate ratios in young and adult mice with and without treatment.

Expression profiling of microRNAs in human bone tissue from postmenopausal women.

PubMed

De-Ugarte, Laura; Serra-Vinardell, Jenny; Nonell, Lara; Balcells, Susana; Arnal, Magdalena; Nogues, Xavier; Mellibovsky, Leonardo; Grinberg, Daniel; Diez-Perez, Adolfo; Garcia-Giralt, Natalia

2018-01-01

Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one physiological condition. The aim of this study was to explore the miRNA expression profile of bone tissue from postmenopausal women. Tissue was obtained from trabecular bone and was analyzed in fresh conditions (n = 6). Primary osteoblasts were also obtained from trabecular bone (n = 4) and human osteoclasts were obtained from monocyte precursors after in vitro differentiation (n = 5). MicroRNA expression profiling was obtained for each sample by microarray and a global miRNA analysis was performed combining the data acquired in all the microarray experiments. From the 641 miRNAs detected in bone tissue samples, 346 (54%) were present in osteoblasts and/or osteoclasts. The other 46% were not identified in any of the bone cells analyzed. Intersection of osteoblast and osteoclast arrays identified 101 miRNAs shared by both cell types, which accounts for 30-40% of miRNAs detected in these cells. In osteoblasts, 266 miRNAs were detected, of which 243 (91%) were also present in the total bone array, representing 38% of all bone miRNAs. In osteoclasts, 340 miRNAs were detected, of which 196 (58%) were also present in the bone tissue array, representing 31% of all miRNAs detected in total bone. These analyses provide an overview of miRNAs expressed in bone tissue, broadening our knowledge in the microRNA field.

A finite element model of the human head for auditory bone conduction simulation.

PubMed

Taschke, Henning; Hudde, Herbert

2006-01-01

In order to investigate the mechanisms of bone conduction, a finite element model of the human head was developed. The most important steps of the modelling process are described. The model was excited by means of percutaneously applied forces in order to get a deeper insight into the way the parts of the peripheral hearing organ and the surrounding tissue vibrate. The analysis is done based on the division of the bone conduction mechanisms into components. The frequency-dependent patterns of vibration of the components are analyzed. Furthermore, the model allows for the calculation of the contribution of each component to the overall bone-conducted sound. The components interact in a complicated way, which strongly depends on the nature of the excitation and the spatial region to which it is applied.

Hydroxyapatite-doped polycaprolactone nanofiber membrane improves tendon-bone interface healing for anterior cruciate ligament reconstruction.

PubMed

Han, Fei; Zhang, Peng; Sun, Yaying; Lin, Chao; Zhao, Peng; Chen, Jiwu

2015-01-01

Hamstring tendon autograft is a routine graft for anterior cruciate ligament (ACL) reconstruction. However, ways of improving the healing between the tendon and bone is often overlooked in clinical practice. This issue can be addressed by using a biomimetic scaffold. Herein, a biomimetic nanofiber membrane of polycaprolactone/nanohydroxyapatite/collagen (PCL/nHAp/Col) is fabricated that mimics the composition of native bone tissue for promoting tendon-bone healing. This membrane has good cytocompatibility, allowing for osteoblast cell adhesion and growth and bone formation. As a result, MC3T3 cells reveal a higher mineralization level in PCL/nHAp/Col membrane compared with PCL membrane alone. Further in vivo studies in ACL reconstruction in a rabbit model shows that PCL/nHAp/Col-wrapped tendon may afford superior tissue integration to nonwrapped tendon in the interface between the tendon and host bone as well as improved mechanical strength. This study shows that PCL/nHAp/Col nanofiber membrane wrapping of autologous tendon is effective for improving tendon healing with host bone in ACL reconstruction.

Mineral metabolism in isolated mouse long bones: Opposite effects of microgravity on mineralization and resorption

NASA Technical Reports Server (NTRS)

Veldhuijzen, Jean Paul; Vanloon, Jack J. W. A.

1994-01-01

An experiment using isolated skeletal tissues under microgravity, is reported. Fetal mouse long bones (metatarsals) were cultured for 4 days in the Biorack facility of Spacelab during the IML-1 (International Microgravity Laboratory) mission of the Space Shuttle. Overall growth was not affected, however glucose consumption was significantly reduced under microgravity. Mineralization of the diaphysis was also strongly reduced under microgravity as compared to the on-board 1 g group. In contrast, mineral resorption by osteoclasts was signficantly increased. These results indicate that these fetal mouse long bones are a sensitive and useful model to further study the cellular mechanisms involved in the changed mineral metabolism of skeletal tissues under microgravity.

Injectable hydrogels for cartilage and bone tissue engineering

PubMed Central

Liu, Mei; Zeng, Xin; Ma, Chao; Yi, Huan; Ali, Zeeshan; Mou, Xianbo; Li, Song; Deng, Yan; He, Nongyue

2017-01-01

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed. PMID:28584674

Do Bone Graft and Cracking of the Sclerotic Cavity Improve Fixation of Titanium and Hydroxyapatite-coated Revision Implants in an Animal Model?

PubMed

Elmengaard, Brian; Baas, Joergen; Jakobsen, Thomas; Kold, Soren; Jensen, Thomas B; Bechtold, Joan E; Soballe, Kjeld

2017-02-01

We previously introduced a manual surgical technique that makes small perforations (cracks) through the sclerotic bone shell that typically forms during the process of aseptic loosening ("crack" revision technique). Perforating just the shell (without violating the proximal cortex) can maintain overall bone continuity while allowing marrow and vascular elements to access the implant surface. Because many revisions require bone graft to fill defects, we wanted to determine if bone graft could further increase implant fixation beyond what we have experimentally shown with the crack technique alone. Also, because both titanium (Ti6Al4V) and hydroxyapatite (HA) implant surfaces are used in revisions, we also wanted to determine their relative effectiveness in this model. We hypothesized that both (1) allografted plasma-sprayed Ti6Al4V; and (2) allografted plasma-sprayed HA-coated implants inserted with a crack revision technique have better fixation compared with a noncrack revision technique in each case. Under approval from our Institutional Animal Care and Use Committee, a female canine animal model was used to evaluate the uncemented revision technique (crack, noncrack) using paired contralateral implants while implant surface (Ti6Al4V, HA) was qualitatively compared between the two (unpaired) series. All groups received bone allograft tightly packed around the implant. This revision model includes a cylindrical implant pistoning 500 μm in a 0.75-mm gap, with polyethylene particles, for 8 weeks. This engenders a bone and tissue response representative of the metaphyseal cancellous region of an aseptically loosened component. At 8 weeks, the original implants were revised and followed for an additional 4 weeks. Mechanical fixation was assessed by load, stiffness, and energy to failure when loaded in axial pushout. Histomorphometry was used to determine the amount and location of bone and fibrous tissue in the grafted gap. The grafted crack revision improved mechanical shear strength, stiffness, and energy to failure (for Ti6Al4V 27- to 69-fold increase and HA twofold increases). The histomorphometric analysis demonstrated primarily fibrous membrane ongrowth and in the gap for the allografted Ti6Al4V noncrack revisions. For allografted HA noncrack revisions, bone ongrowth at the implant surface was observed, but fibrous tissue also was present in the inner gap. Although both Ti6Al4V and HA surfaces showed improved fixation with grafted crack revision, and Ti6Al4V achieved the highest percent gain, HA demonstrated the strongest overall fixation. The results of this study suggest that novel osteoconductive or osteoinductive coatings and bone graft substitutes or tissue-engineered constructs may further improve bone-implant fixation with the crack revision technique but require evaluation in a rigorous model such as presented here. This experimental study provides data on which to base clinical trials aimed to improve fixation of revision implants. Given the multifactorial nature of complex human revisions, such a protocoled clinical study is required to determine the clinical applicability of this approach.

Bone tissue formation in extraction sockets from sites with advanced periodontal disease: a histomorphometric study in humans.

PubMed

Ahn, Jae-Jin; Shin, Hong-In

2008-01-01

To investigate postextraction bone formation over time in both diseased and healthy sockets. Core specimens of healing tissues following tooth extraction were obtained at the time of implant placement in patients treated between October 2005 and December 2007. A disease group and a control group were classified according to socket examination at the time of extraction. The biopsy specimens were analyzed histomorphometrically to measure the dimensional changes among 3 tissue types: epithelial layer, connective tissue area, and new bone tissue area. Fifty-five specimens from sites of previously advanced periodontal disease from 45 patients were included in the disease group. Another 12 specimens of previously healthy extraction sockets were collected from 12 different patients as a control. The postextraction period of the disease group varied from 2 to 42 weeks. In the disease group, connective tissue occupied most of the socket during the first 4 weeks. New bone area progressively replaced the connective tissue area after the first 4 weeks. The area proportion of new bone tissue exceeded that of connective tissue by 14 weeks. After 20 weeks, most extraction sockets in the disease group demonstrated continuous new bone formation. The control group exhibited almost complete socket healing after 10 weeks, with no more new bone formation after 20 weeks. Osseous regeneration in the diseased sockets developed more slowly than in the disease-free sockets. After 16 weeks, new bone area exceeded 50% of the total newly regenerated tissue in the sockets with severe periodontal destruction. In the control group, after 8 weeks, new bone area exceeded 50% of the total tissue.

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.

Two Stage Repair of Composite Craniofacial Defects with Antibiotic Releasing Porous Poly(methyl methacrylate) Space Maintainers and Bone Regeneration

NASA Astrophysics Data System (ADS)

Spicer, Patrick

Craniofacial defects resulting from trauma and resection present many challenges to reconstruction due to the complex structure, combinations of tissues, and environment, with exposure to the oral, skin and nasal mucosal pathogens. Tissue engineering seeks to regenerate the tissues lost in these defects; however, the composite nature and proximity to colonizing bacteria remain difficult to overcome. Additionally, many tissue engineering approaches have further hurdles to overcome in the regulatory process to clinical translation. As such these studies investigated a two stage strategy employing an antibiotic-releasing porous polymethylmethacrylate space maintainer fabricated with materials currently part of products approved or cleared by the United States Food and Drug Administration, expediting the translation to the clinic. This porous space maintainer holds the bone defect open allowing soft tissue to heal around the defect. The space maintainer can then be removed and one regenerated in the defect. These studies investigated the individual components of this strategy. The porous space maintainer showed similar soft tissue healing and response to non-porous space maintainers in a rabbit composite tissue defect. The antibiotic-releasing space maintainers showed release of antibiotics from 1-5 weeks, which could be controlled by loading and fabrication parameters. In vivo, space maintainers releasing a high dose of antibiotics for an extended period of time increased soft tissue healing over burst release space maintainers in an infected composite tissue defect model in a rabbit mandible. Finally, stabilization of bone defects and regeneration could be improved through scaffold structures and delivery of a bone forming growth factor. These studies illustrate the possibility of the two stage strategy for repair of composite tissue defects of the craniofacial complex.

Aging Periosteal Progenitor Cells have Reduced Regenerative Responsiveness to Bone Injury and to the Anabolic Actions of PTH 1-34 Treatment

PubMed Central

Yukata, Kiminori; Xie, Chao; Li, Tian-Fang; Takahata, Masahiko; Hoak, Donna; Kondabolu, Sirish; Zhang, Xinping; Awad, Hani A.; Schwarz, Edward M.; Beck, Christopher A.; Jonason, Jennifer H.; O’Keefe, Regis J.

2014-01-01

A stabilized tibia fracture model was used in young (8-week old) and aged (1-year old) mice to define the relative bone regenerative potential and the relative responsiveness of the periosteal progenitor population with aging and PTH 1-34 (PTH) systemic therapy. Bone regeneration was assessed through gene expressions, radiographic imaging, histology/histomorphometry, and biomechanical testing. Radiographs and microCT showed increased calcified callus tissue and enhanced bone healing in young compared to aged mice. A key mechanism involved reduced proliferation, expansion, and differentiation of periosteal progenitor cell populations in aged mice. The experiments showed that PTH increased calcified callus tissue and torsional strength with a greater response in young mice. Histology and quantitative histomorphometry confirmed that PTH increased callus tissue area due primarily to an increase in bone formation, since minimal changes in cartilage and mesenchyme tissue area occurred. Periosteum examined at 3, 5, and 7 days showed that PTH increased cyclin D1 expression, the total number of cells in the periosteum, and width of the periosteal regenerative tissue. Gene expression showed that aging delayed differentiation of both bone and cartilage tissues during fracture healing. PTH resulted in sustained Col10a1 expression consistent with delayed chondrocyte maturation, but otherwise minimally altered cartilage gene expression. In contrast, PTH 1-34 stimulated expression of Runx2 and Osterix, but resulted in reduced Osteocalcin. β-catenin staining was present in mesenchymal chondroprogenitors and chondrocytes in early fracture healing, but was most intense in osteoblastic cells at later times. PTH increased active β-catenin staining in the osteoblast populations of both young and aged mice, but had a lesser effect in cartilage. Altogether the findings show that reduced fracture healing in aging involves decreased proliferation and differentiation of stem cells lining the bone surface. While PTH 1-34 enhances the proliferation and expansion of the periosteal stem cell population and accelerates bone formation and fracture healing, the effects are proportionately reduced in aged mice compared to young mice. β-catenin is induced by PTH in early and late fracture healing and is a potential target of PTH 1-34 effects. PMID:24530870

The biomechanical behavior on the interface of tumor arthrosis/allograft prosthetic composite by finite element analysis

NASA Astrophysics Data System (ADS)

Chen, H. Z.; Jiang, W.; Zou, W.; Luo, J. M.; Chen, J. Y.; Tu, C. Q.; Xing, B. B.; Gu, Z. W.; Zhang, X. D.

2008-11-01

The biomechanical behavior of the uniting interface between the allograft bone and the autogenetic bone plays an important role in the treatment of the proximal femur massive defects with artificial tumor arthrosis/allograft prosthetic composite (TAAPC). According to the CT data of a patient, a 3D medical treatment model of TAAPC was established. Under the loads of 1.5 and 2.5 times standard body weight (70 kg), the mechanical behavior of the treatment model was analyzed by finite element analysis (FEA) for three typical healing periods. The results show that there are significant differences in the stress values and distribution in different healing periods. With healing of osteotomy, the hardness of the tissue of the uniting interface increases, the stress in uniting area was increased greatly and the stress concentration decreased. After cured the stress almost reached the level of normal bone. In the initial stage of healing, the healing training is not encouraged because there is an obvious risk of fracture of prosthesis and bone cement. In addition, porous hydroxyapatite (HA) ceramic used as bone tissue scaffold for this case, not only facilitates the generation of new bone, but also can avoid this risk caused by the non-uniting interface.

Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing.

PubMed

Vasconcelos, Daniela P; Costa, Madalena; Neves, Nuno; Teixeira, José H; Vasconcelos, Daniel M; Santos, Susana G; Águas, Artur P; Barbosa, Mário A; Barbosa, Judite N

2018-06-01

The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch + RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed. These results suggest that Ch scaffolds embedded with RvD1 were able to lead to the formation of new bone with improvement of trabecular thickness. This study shows that the presence of RvD1 in the acute phase of the inflammatory response to the implanted biomaterial had a positive role in the subsequent bone tissue repair, thus demonstrating the importance of innovative approaches for the control of immune responses to biomedical implants in the design of advanced strategies for regenerative medicine. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1626-1633, 2018. © 2018 Wiley Periodicals, Inc.

Periosteum tissue engineering in an orthotopic in vivo platform.

PubMed

Baldwin, J G; Wagner, F; Martine, L C; Holzapfel, B M; Theodoropoulos, C; Bas, O; Savi, F M; Werner, C; De-Juan-Pardo, E M; Hutmacher, D W

2017-03-01

The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated. In this study, we present a novel periosteum tissue engineering concept utilizing a multiphasic scaffold design in combination with different human cell types for periosteal regeneration in an orthotopic in vivo platform. Human endothelial and bone marrow mesenchymal stem cells (BM-MSCs) were used to mirror both the vascular and osteogenic niche respectively. Immunohistochemistry showed that the BM-MSCs maintained their undifferentiated phenotype. The human endothelial cells developed into mature vessels and connected to host vasculature. The addition of an in vitro engineered endothelial network increased vascularization in comparison to cell-free constructs. Altogether, the results showed that the human TEPC (hTEPC) successfully recapitulated the osteogenic and vascular niche of native periosteum, and that the presented orthotopic xenograft model provides a suitable in vivo environment for evaluating scaffold-based tissue engineering concepts exploiting human cells. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

A comparison between anisotropic analytical and multigrid superposition dose calculation algorithms in radiotherapy treatment planning

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

Wu, Vincent W.C., E-mail: htvinwu@polyu.edu.hk; Tse, Teddy K.H.; Ho, Cola L.M.

2013-07-01

Monte Carlo (MC) simulation is currently the most accurate dose calculation algorithm in radiotherapy planning but requires relatively long processing time. Faster model-based algorithms such as the anisotropic analytical algorithm (AAA) by the Eclipse treatment planning system and multigrid superposition (MGS) by the XiO treatment planning system are 2 commonly used algorithms. This study compared AAA and MGS against MC, as the gold standard, on brain, nasopharynx, lung, and prostate cancer patients. Computed tomography of 6 patients of each cancer type was used. The same hypothetical treatment plan using the same machine and treatment prescription was computed for each casemore » by each planning system using their respective dose calculation algorithm. The doses at reference points including (1) soft tissues only, (2) bones only, (3) air cavities only, (4) soft tissue-bone boundary (Soft/Bone), (5) soft tissue-air boundary (Soft/Air), and (6) bone-air boundary (Bone/Air), were measured and compared using the mean absolute percentage error (MAPE), which was a function of the percentage dose deviations from MC. Besides, the computation time of each treatment plan was recorded and compared. The MAPEs of MGS were significantly lower than AAA in all types of cancers (p<0.001). With regards to body density combinations, the MAPE of AAA ranged from 1.8% (soft tissue) to 4.9% (Bone/Air), whereas that of MGS from 1.6% (air cavities) to 2.9% (Soft/Bone). The MAPEs of MGS (2.6%±2.1) were significantly lower than that of AAA (3.7%±2.5) in all tissue density combinations (p<0.001). The mean computation time of AAA for all treatment plans was significantly lower than that of the MGS (p<0.001). Both AAA and MGS algorithms demonstrated dose deviations of less than 4.0% in most clinical cases and their performance was better in homogeneous tissues than at tissue boundaries. In general, MGS demonstrated relatively smaller dose deviations than AAA but required longer computation time.« less

Trabecular bone strains around a dental implant and associated micromotions--a micro-CT-based three-dimensional finite element study.

PubMed

Limbert, Georges; van Lierde, Carl; Muraru, O Luiza; Walboomers, X Frank; Frank, Milan; Hansson, Stig; Middleton, John; Jaecques, Siegfried

2010-05-07

The first objective of this computational study was to assess the strain magnitude and distribution within the three-dimensional (3D) trabecular bone structure around an osseointegrated dental implant loaded axially. The second objective was to investigate the relative micromotions between the implant and the surrounding bone. The work hypothesis adopted was that these virtual measurements would be a useful indicator of bone adaptation (resorption, homeostasis, formation). In order to reach these objectives, a microCT-based finite element model of an oral implant implanted into a Berkshire pig mandible was developed along with a robust software methodology. The finite element mesh of the 3D trabecular bone architecture was generated from the segmentation of microCT scans. The implant was meshed independently from its CAD file obtained from the manufacturer. The meshes of the implant and the bone sample were registered together in an integrated software environment. A series of non-linear contact finite element (FE) analyses considering an axial load applied to the top of the implant in combination with three sets of mechanical properties for the trabecular bone tissue was devised. Complex strain distribution patterns are reported and discussed. It was found that considering the Young's modulus of the trabecular bone tissue to be 5, 10 and 15GPa resulted in maximum peri-implant bone microstrains of about 3000, 2100 and 1400. These results indicate that, for the three sets of mechanical properties considered, the magnitude of maximum strain lies within an homeostatic range known to be sufficient to maintain/form bone. The corresponding micro-motions of the implant with respect to the bone microstructure were shown to be sufficiently low to prevent fibrous tissue formation and to favour long-term osseointegration. Copyright 2010 Elsevier Ltd. All rights reserved.

Does cone beam CT actually ameliorate stab wound analysis in bone?

PubMed

Gaudio, D; Di Giancamillo, M; Gibelli, D; Galassi, A; Cerutti, E; Cattaneo, C

2014-01-01

This study aims at verifying the potential of a recent radiological technology, cone beam CT (CBCT), for the reproduction of digital 3D models which may allow the user to verify the inner morphology of sharp force wounds within the bone tissue. Several sharp force wounds were produced by both single and double cutting edge weapons on cancellous and cortical bone, and then acquired by cone beam CT scan. The lesions were analysed by different software (a DICOM file viewer and reverse engineering software). Results verified the limited performances of such technology for lesions made on cortical bone, whereas on cancellous bone reliable models were obtained, and the precise morphology within the bone tissues was visible. On the basis of such results, a method for differential diagnosis between cutmarks by sharp tools with a single and two cutting edges can be proposed. On the other hand, the metrical computerised analysis of lesions highlights a clear increase of error range for measurements under 3 mm. Metric data taken by different operators shows a strong dispersion (% relative standard deviation). This pilot study shows that the use of CBCT technology can improve the investigation of morphological stab wounds on cancellous bone. Conversely metric analysis of the lesions as well as morphological analysis of wound dimension under 3 mm do not seem to be reliable.

Physiology of Mechanotransduction: How Do Muscle and Bone "Talk" to One Another?

PubMed

Isaacson, Janalee; Brotto, Marco

2014-06-01

The complexity of cell interactions with their microenvironment and their ability to communicate at the autocrine, paracrine, and endocrine levels has gradually but significantly evolved in the last three decades. The musculoskeletal system has been historically recognized to be governed by a relationship of proximity and function, chiefly dictated by mechanical forces and the work of gravity itself. In this review article, we first provide a historical overview of the biomechanical theory of bone- muscle interactions. Next, we expand to detail the significant evolution in our understanding of the function of bones and muscles as secretory organs. Then, we review and discuss new evidence in support of a biochemical interaction between these two tissues. We then propose that these two models of interaction are complementary and intertwined providing for a new frontier for the investigation of how bone-muscle cross talk could be fully explored for the targeting of new therapies for musculoskeletal diseases, particularly the twin conditions of aging, osteoporosis and sarcopenia. In the last section, we explore the bone-muscle cross talk in the context of their interactions with other tissues and the global impact of these multi-tissue interactions on chronic diseases.

Comparison of 3D bone models of the knee joint derived from CT and 3T MR imaging.

PubMed

Neubert, Aleš; Wilson, Katharine J; Engstrom, Craig; Surowiec, Rachel K; Paproki, Anthony; Johnson, Nicholas; Crozier, Stuart; Fripp, Jurgen; Ho, Charles P

2017-08-01

To examine whether magnetic resonance (MR) imaging can offer a viable alternative to computed tomography (CT) based 3D bone modeling. CT and MR (SPACE, TrueFISP, VIBE) images were acquired from the left knee joint of a fresh-frozen cadaver. The distal femur, proximal tibia, proximal fibula and patella were manually segmented from the MR and CT examinations. The MR bone models obtained from manual segmentations of all three sequences were compared to CT models using a similarity measure based on absolute mesh differences. The average absolute distance between the CT and the various MR-based bone models were all below 1mm across all bones. The VIBE sequence provided the best agreement with the CT model, followed by the SPACE, then the TrueFISP data. The most notable difference was for the proximal tibia (VIBE 0.45mm, SPACE 0.82mm, TrueFISP 0.83mm). The study indicates that 3D MR bone models may offer a feasible alternative to traditional CT-based modeling. A single radiological examination using the MR imaging would allow simultaneous assessment of both bones and soft-tissues, providing anatomically comprehensive joint models for clinical evaluation, without the ionizing radiation of CT imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

RESPONSE FUNCTIONS FOR COMPUTING ABSORBED DOSE TO SKELETAL TISSUES FROM NEUTRON IRRADIATION

PubMed Central

Bahadori, Amir A.; Johnson, Perry; Jokisch, Derek W.; Eckerman, Keith F.; Bolch, Wesley E.

2016-01-01

Spongiosa in the adult human skeleton consists of three tissues - active marrow (AM), inactive marrow (IM), and trabecularized mineral bone (TB). Active marrow is considered to be the target tissue for assessment of both long-term leukemia risk and acute marrow toxicity following radiation exposure. The total shallow marrow (TM50), defined as all tissues laying within the first 50 μm the bone surfaces, is considered to be the radiation target tissue of relevance for radiogenic bone cancer induction. For irradiation by sources external to the body, kerma to homogeneous spongiosa has been used as a surrogate for absorbed dose to both of these tissues, as direct dose calculations are not possible using computational phantoms with homogenized spongiosa. Recent microCT imaging of a 40-year-old male cadaver has allowed for the accurate modeling of the fine microscopic structure of spongiosa in many regions of the adult skeleton [Hough et al PMB (2011)]. This microstructure, along with associated masses and tissue compositions, was used to compute specific absorbed fractions (SAF) values for protons originating in axial and appendicular bone sites [Jokisch et al PMB (submitted)]. These proton SAFs, bone masses, tissue compositions, and proton production cross-sections, were subsequently used to construct neutron dose response functions (DRFs) for both AM and TM50 targets in each bone of the reference adult male. Kerma conditions were assumed for other resultant charged particles. For comparison, active marrow, total shallow marrow, and spongiosa kerma coefficients were also calculated. At low incident neutron energies, AM kerma coefficients for neutrons correlate well with values of the AM DRF, while total marrow (TM) kerma coefficients correlate well with values of the TM50 DRF. At high incident neutron energies, all kerma coefficients and DRFs tend to converge as charged particle equilibrium (CPE) is established across the bone site. In the range of 10 eV to 100 MeV, substantial differences are observed among the kerma coefficients and DRF. As a result, it is recommended that the AM kerma coefficient be used to estimate the AM DRF, and that the TM kerma coefficient be used to estimate the TM50 DRF below 10 eV. Between 10 eV and 100 MeV, the appropriate DRF should be used as presented in this study. Above 100 MeV, spongiosa kerma coefficients apply well for estimating skeletal tissue doses. DRF values for each bone site as a function of energy are provided in an electronic annex to this article. PMID:21983525

Space research on organs and tissues

NASA Technical Reports Server (NTRS)

Tischler, Marc E.; Morey-Holton, Emily

1992-01-01

The effects of microgravity on various physiological systems are reviewed focusing on muscle, bone, cardiovascular, pulmonary, neurovestibular, liver, and endocrine systems. It is noted that certain alterations of organs and tissues caused by microgravity are not reproducible in earth-bound animal or human models. Thus space research on organs and tissues is essential for both validating the earth-bound models used in laboratories and studying the adaptations to weightlessness which cannot be mimicked on earth.

Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

PubMed

Pina, Sandra; Oliveira, Joaquim M; Reis, Rui L

2015-02-18

Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rethinking the nature of fibrolamellar bone: an integrative biological revision of sauropod plexiform bone formation.

PubMed

Stein, Koen; Prondvai, Edina

2014-02-01

We present novel findings on sauropod bone histology that cast doubt on general palaeohistological concepts concerning the true nature of woven bone in primary cortical bone and its role in the rapid growth and giant body sizes of sauropod dinosaurs. By preparing and investigating longitudinal thin sections of sauropod long bones, of which transverse thin sections were published previously, we found that the amount of woven bone in the primary complex has been largely overestimated. Using comparative cellular and light-extinction characteristics in the two section planes, we revealed that the majority of the bony lamina consists of longitudinally organized primary bone, whereas woven bone is usually represented only by a layer a few cells thin in the laminae. Previous arguments on sauropod biology, which have been based on the overestimated amount, misinterpreted formation process and misjudged role of woven bone in the plexiform bone formation of sauropod dinosaurs, are thereby rejected. To explain the observed pattern in fossil bones, we review the most recent advances in bone biology concerning bone formation processes at the cellular and tissue levels. Differentiation between static and dynamic osteogenesis (SO and DO) and the revealed characteristics of SO- versus DO-derived bone tissues shed light on several questions raised by our palaeohistological results and permit identification of these bone tissues in fossils with high confidence. By presenting the methods generally used for investigating fossil bones, we show that the major cause of overestimation of the amount of woven bone in previous palaeohistological studies is the almost exclusive usage of transverse sections. In these sections, cells and crystallites of the longitudinally organized primary bone are cut transversely, thus cells appear rounded and crystallites remain dark under crossed plane polarizers, thereby giving the false impression of woven bone. In order to avoid further confusion in palaeohistological studies, we introduce new osteohistological terms as well as revise widely used but incorrect terminology. To infer the role of woven bone in the bone formation of fast-growing tetrapods, we review some aspects of the interrelationships between the vascularity of bone tissues, basal metabolic rate, body size and growth rate. By putting our findings into the context of osteogenesis, we provide a new model for the diametrical limb bone growth of sauropods and present new implications for the evolution of fast growth in vertebrates. Since biomechanical studies of bone tissues suggest that predominant collagen fibre orientation (CFO) is controlled by endogenous, functional and perhaps phylogenetic factors, the relationship between CFO and bone growth rate as defined by Amprino's rule, which has been the basis for the biological interpretation of several osteohistological features, must be revised. Our findings draw attention to the urgent need for revising widely accepted basic concepts of palaeohistological studies, and for a more integrative approach to bone formation, biomechanics and bone microstructural features of extant and extinct vertebrates to infer life history traits of long extinct, iconic animals like dinosaurs. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

Use of Animal Models in Understanding Cancer-induced Bone Pain

PubMed Central

Slosky, Lauren M; Largent-Milnes, Tally M; Vanderah, Todd W

2015-01-01

Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP’s unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP. PMID:26339191

Investigation, sensitivity analysis, and multi-objective optimization of effective parameters on temperature and force in robotic drilling cortical bone.

PubMed

Tahmasbi, Vahid; Ghoreishi, Majid; Zolfaghari, Mojtaba

2017-11-01

The bone drilling process is very prominent in orthopedic surgeries and in the repair of bone fractures. It is also very common in dentistry and bone sampling operations. Due to the complexity of bone and the sensitivity of the process, bone drilling is one of the most important and sensitive processes in biomedical engineering. Orthopedic surgeries can be improved using robotic systems and mechatronic tools. The most crucial problem during drilling is an unwanted increase in process temperature (higher than 47 °C), which causes thermal osteonecrosis or cell death and local burning of the bone tissue. Moreover, imposing higher forces to the bone may lead to breaking or cracking and consequently cause serious damage. In this study, a mathematical second-order linear regression model as a function of tool drilling speed, feed rate, tool diameter, and their effective interactions is introduced to predict temperature and force during the bone drilling process. This model can determine the maximum speed of surgery that remains within an acceptable temperature range. Moreover, for the first time, using designed experiments, the bone drilling process was modeled, and the drilling speed, feed rate, and tool diameter were optimized. Then, using response surface methodology and applying a multi-objective optimization, drilling force was minimized to sustain an acceptable temperature range without damaging the bone or the surrounding tissue. In addition, for the first time, Sobol statistical sensitivity analysis is used to ascertain the effect of process input parameters on process temperature and force. The results show that among all effective input parameters, tool rotational speed, feed rate, and tool diameter have the highest influence on process temperature and force, respectively. The behavior of each output parameters with variation in each input parameter is further investigated. Finally, a multi-objective optimization has been performed considering all the aforementioned parameters. This optimization yielded a set of data that can considerably improve orthopedic osteosynthesis outcomes.

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

Microcracks induce osteoblast alignment and maturation on hydroxyapatite scaffolds

NASA Astrophysics Data System (ADS)

Shu, Yutian

Physiological bone tissue is a mineral/collagen composite with a hierarchical structure. The features in bone, such as mineral crystals, fibers, and pores can range from the nanometer to the centimeter in size. Currently available bone tissue scaffolds primarily address the chemical composition, pore size, and pore size distribution. While these design parameters are extensively investigated for mimicking bone function and inducing bone regeneration, little is known about microcracks, which is a prevalent feature found in fractured bone in vivo and associated with fracture healing and repair. Since the purpose of bone tissue engineering scaffold is to enhance bone regeneration, the coincidence of microcracks and bone densification should not be neglected but rather be considered as a potential parameter in bone tissue engineering scaffold design. The purpose of this study is to test the hypothesis that microcracks enhance bone healing. In vitro studies were designed to investigate the osteoblast (bone forming cells) response to microcracks in dense (94%) hydroxyapatite substrates. Microcracks were introduced using a well-established Vickers indentation technique. The results of our study showed that microcracks induced osteoblast alignment, enhanced osteoblast attachment and more rapid maturation. These findings may provide insight into fracture healing mechanism(s) as well as improve the design of bone tissue engineering orthopedic scaffolds for more rapid bone regeneration.

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

Ultrastructural analysis of metal particles released from stainless steel and titanium miniplate components in an animal model.

PubMed

Matthew, I R; Frame, J W

1998-01-01

Low-vacuum scanning electron microscopy (Ivac SEM) was used to characterize the appearance of metal particles released from stressed and unstressed Champy miniplates placed in dogs and to study the relationship of the debris to the surrounding tissues. Under general endotracheal anesthesia, two Champy miniplates (titanium or stainless steel) were placed on the frontal bone in an animal model. One miniplate was bent to fit the curvature of the frontal bone (unstressed) and another miniplate of the same material was bent in a curve until the midpoint was raised 3 mm above the ends. The latter miniplate adapted to the skull curvature under tension during screw insertion (stressed). The miniplates and surrounding tissues were retrieved after intervals of 4, 12, and 24 weeks. Decalcified sections were prepared and examined by light microscopy and Ivac SEM. Under Ivac SEM examination, the titanium particles had a smooth, polygonal outline. Stainless steel particles were typically spherical, with numerous small projections on the surface. Most particles were 1 to 10 microns in diameter. The tissue response to the particles was variable; some particles were covered by fibrous connective tissue or enclosed by bone, and others were intracellular. The metal particles released from stressed or unstressed Champy miniplates were similar, and this was related to their source of origin and duration within the tissues. The tissue response to the particles appeared to depend on their location.

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.

Fracture healing: mechanisms and interventions

PubMed Central

Einhorn, Thomas A.; Gerstenfeld, Louis C.

2015-01-01

Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed. PMID:25266456

Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model

PubMed Central

Turley, Sean M; Thambyah, Ashvin; Riggs, Christopher M; Firth, Elwyn C; Broom, Neil D

2014-01-01

The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid-condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard-tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage. PMID:24689513

Integration of 3D Printed and Micropatterned Polycaprolactone Scaffolds for Guidance of Oriented Collagenous Tissue Formation In Vivo.

PubMed

Pilipchuk, Sophia P; Monje, Alberto; Jiao, Yizu; Hao, Jie; Kruger, Laura; Flanagan, Colleen L; Hollister, Scott J; Giannobile, William V

2016-03-01

Scaffold design incorporating multiscale cues for clinically relevant, aligned tissue regeneration has potential to improve structural and functional integrity of multitissue interfaces. The objective of this preclinical study is to develop poly(ε-caprolactone) (PCL) scaffolds with mesoscale and microscale architectural cues specific to human ligament progenitor cells and assess their ability to form aligned bone-ligament-cementum complexes in vivo. PCL scaffolds are designed to integrate a 3D printed bone region with a micropatterned PCL thin film consisting of grooved pillars. The patterned film region is seeded with human ligament cells, fibroblasts transduced with bone morphogenetic protein-7 genes seeded within the bone region, and a tooth dentin segment positioned on the ligament region prior to subcutaneous implantation into a murine model. Results indicate increased tissue alignment in vivo using micropatterned PCL films, compared to random-porous PCL. At week 6, 30 μm groove depth significantly enhances oriented collagen fiber thickness, overall cell alignment, and nuclear elongation relative to 10 μm groove depth. This study demonstrates for the first time that scaffolds with combined hierarchical mesoscale and microscale features can align cells in vivo for oral tissue repair with potential for improving the regenerative response of other bone-ligament complexes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Current status of bone/cartilage tissue engineering towards clinical applications].

PubMed

Ohgushi, Hajime

2014-10-01

Osteo/chondrogenic differentiation capabilities are seen after in vivo implantation of mesenchymal stem cells (MSCs), which are currently used for the patients having bone/cartilage defects. Importantly, the differentiation capabilities are induced by culturing technology, resulting in in vitro bone/cartilage formation. Especially, the in vitro bone tissue is useful for bone tissue regeneration. For cartilage regeneration, culture expanded chondrocytes derived from patient's normal cartilage are also used for the patients having cartilage damages. Recently, the cultured chondrocytes embedded in atelocollagen gel are obtainable as tissue engineered products distributed by Japan Tissue Engineering Co. Ltd. The products are available in the well-regulated hospitals by qualified orthopedic surgeons. The criteria for these hospitals/surgeons have been established. This review paper focuses on current status of bone/cartilage tissue engineering towards clinical applications in Japan.

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.

The application of porous tantalum cylinder to the repair of comminuted bone defects: a study of rabbit firearm injuries

PubMed Central

Ren, Bo; Zhai, Zhenbo; Guo, Kai; Liu, Yanpu; Hou, Weihuan; Zhu, Qingsheng; Zhu, Jinyu

2015-01-01

The aim of this study is to investigate the effect of porous tantalum material in repair tibial defects caused by firearm injuries in a rabbit model. A multifunctional biological impact machine was used to establish a rabbit tibial defect model of firearm injury. Porous tantalum rods were processed into a hollow cylinder. Kirschner wires were used for intramedullary fixation. We compared the differences of the bone ingrowth of the porous tantalum material by gross observations, X-rays and histological evaluations. The radiographic observations revealed that fibrous tissue covered the material surface after 4 weeks, and periosteal reactions and new bone callus extending materials appeared after 8 weeks. After 16 weeks, the calluses of the firearm injury group were completely wrapped around a porous tantalum material. The group with the highest Lane-Sandhu X-rays cores was the firearm injury and tantalum implant group, and the blank control group exhibited the lowest scores. The histological evaluations revealed that the presence of new bone around the biomaterial had grown into the porous tantalum. By the 16th week, the areas of bone tissue of the firearm injury group was significant higher than that of non-firearm injury group (P<0.05). The comminuted fractures treated with tantalum cylinders exhibited greater bone ingrowth in the firearm injury group. In conditions of firearm injuries, the porous tantalum biomaterial exhibited bone ingrowth that was beneficial to the treatment of bone defects. PMID:26131078

Bone tissue engineering: a review in bone biomimetics and drug delivery strategies.

PubMed

Porter, Joshua R; Ruckh, Timothy T; Popat, Ketul C

2009-01-01

Critical-sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue-engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical-sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF-betas, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

Translational Research: Palatal-derived Ecto-mesenchymal Stem Cells from Human Palate: A New Hope for Alveolar Bone and Cranio-Facial Bone Reconstruction

PubMed Central

Grimm, Wolf Dieter; Dannan, Aous; Giesenhagen, Bernd; Schau, Ingmar; Varga, Gabor; Vukovic, Mark Alexander; Sirak, Sergey Vladimirovich

2014-01-01

The management of facial defects has rapidly changed in the last decade. Functional and esthetic requirements have steadily increased along with the refinements of surgery. In the case of advanced atrophy or jaw defects, extensive horizontal and vertical bone augmentation is often unavoidable to enable patients to be fitted with implants. Loss of vertical alveolar bone height is the most common cause for a non primary stability of dental implants in adults. At present, there is no ideal therapeutic approach to cure loss of vertical alveolar bone height and achieve optimal pre-implantological bone regeneration before dental implant placement. Recently, it has been found that specific populations of stem cells and/or progenitor cells could be isolated from different dental resources, namely the dental follicle, the dental pulp and the periodontal ligament. Our research group has cultured palatal-derived stem cells (paldSCs) as dentospheres and further differentiated into various cells of the neuronal and osteogenic lineage, thereby demonstrating their stem cell state. In this publication will be shown whether paldSCs could be differentiated into the osteogenic lineage and, if so, whether these cells are able to regenerate alveolar bone tissue in vivo in an athymic rat model. Furthermore, using these data we have started a proof of principle clinical- and histological controlled study using stem cell-rich palatal tissues for improving the vertical alveolar bone augmentation in critical size defects. The initial results of the study demonstrate the feasibility of using stem cell-mediated tissue engineering to treat alveolar bone defects in humans. PMID:24921024

Adipose-derived stem cells and periodontal tissue engineering.

PubMed

Tobita, Morikuni; Mizuno, Hiroshi

2013-01-01

Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology

PubMed Central

Bodle, Josephine C.; Hanson, Ariel D.

2011-01-01

This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application. PMID:21338267

The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering

PubMed Central

Li, Peiqi; Hashimoto, Yoshiya; Honda, Yoshitomo; Arima, Yoshiyuki; Matsumoto, Naoyuki

2015-01-01

Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN)-γ and zoledronate (Zol) are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS). At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment) groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption. PMID:26516841

Numerical Simulation of Shock Wave Propagation in Fractured Cortical Bone

NASA Astrophysics Data System (ADS)

Padilla, Frédéric; Cleveland, Robin

2009-04-01

Shock waves (SW) are considered a promising method to treat bone non unions, but the associated mechanisms of action are not well understood. In this study, numerical simulations are used to quantify the stresses induced by SWs in cortical bone tissue. We use a 3D FDTD code to solve the linear lossless equations that describe wave propagation in solids and fluids. A 3D model of a fractured rat femur was obtained from micro-CT data with a resolution of 32 μm. The bone was subject to a plane SW pulse with a peak positive pressure of 40 MPa and peak negative pressure of -8 MPa. During the simulations the principal tensile stress and maximum shear stress were tracked throughout the bone. It was found that the simulated stresses in a transverse plane relative to the bone axis may reach values higher than the tensile and shear strength of the bone tissue (around 50 MPa). These results suggest that the stresses induced by the SW may be large enough to initiate local micro-fractures, which may in turn trigger the start of bone healing for the case of a non union.

Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.

PubMed

Yasui, M; Shiraishi, Y; Ozaki, N; Hayashi, K; Hori, K; Ichiyanagi, M; Sugiura, Y

2012-08-01

To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing. © 2011 European Federation of International Association for the Study of Pain Chapters.

Engineering complex orthopaedic tissues via strategic biomimicry.

PubMed

Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

2015-03-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will enable integrative and functional repair of soft tissue injuries, and moreover, lay the foundation for the development of composite tissue systems and ultimately, total limb or joint regeneration.

Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

PubMed Central

Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

2014-01-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will enable integrative and functional repair of soft tissue injuries, and moreover, lay the foundation for the development of composite tissue systems and ultimately, total limb or joint regeneration. PMID:25465616

Automated Bone Segmentation and Surface Evaluation of a Small Animal Model of Post-Traumatic Osteoarthritis.

PubMed

Ramme, Austin J; Voss, Kevin; Lesporis, Jurinus; Lendhey, Matin S; Coughlin, Thomas R; Strauss, Eric J; Kennedy, Oran D

2017-05-01

MicroCT imaging allows for noninvasive microstructural evaluation of mineralized bone tissue, and is essential in studies of small animal models of bone and joint diseases. Automatic segmentation and evaluation of articular surfaces is challenging. Here, we present a novel method to create knee joint surface models, for the evaluation of PTOA-related joint changes in the rat using an atlas-based diffeomorphic registration to automatically isolate bone from surrounding tissues. As validation, two independent raters manually segment datasets and the resulting segmentations were compared to our novel automatic segmentation process. Data were evaluated using label map volumes, overlap metrics, Euclidean distance mapping, and a time trial. Intraclass correlation coefficients were calculated to compare methods, and were greater than 0.90. Total overlap, union overlap, and mean overlap were calculated to compare the automatic and manual methods and ranged from 0.85 to 0.99. A Euclidean distance comparison was also performed and showed no measurable difference between manual and automatic segmentations. Furthermore, our new method was 18 times faster than manual segmentation. Overall, this study describes a reliable, accurate, and automatic segmentation method for mineralized knee structures from microCT images, and will allow for efficient assessment of bony changes in small animal models of PTOA.

Ex vivo culture platform for assessment of cartilage repair treatment strategies.

PubMed

Schwab, Andrea; Meeuwsen, Annick; Ehlicke, Franziska; Hansmann, Jan; Mulder, Lars; Smits, Anthal; Walles, Heike; Kock, Linda

2017-01-01

There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors specific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we evaluated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, matrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivo testing.

Role of structural anisotropy of biological tissues in poroelastic wave propagation

PubMed Central

Cardoso, Luis; Cowin, Stephen C.

2011-01-01

Ultrasound waves have a broad range of clinical applications as a non-destructive testing approach in imaging and in the diagnoses of medical conditions. Generally, biological tissues are modeled as an homogenized equivalent medium with an apparent density through which a single wave propagates. Only the first wave arriving at the ultrasound probe is used for the measurement of the speed of sound. However, the existence of a second wave in tissues such as cancellous bone has been reported and its existence is an unequivocal signature of Biot type poroelastic media. To account for the fact that ultrasound is sensitive to microarchitecture as well as density, a fabric-dependent anisotropic poroelastic ultrasound (PEU) propagation theory was recently developed. Key to this development was the inclusion of the fabric tensor - a quantitative stereological measure of the degree of structural anisotropy of bone - into the linear poroelasticity theory. In the present study, this framework is extended to the propagation of waves in several soft and hard tissues. It was found that collagen fibers in soft tissues and the mineralized matrix in hard tissues are responsible for the anisotropy of the solid tissue constituent through the fabric tensor in the model. PMID:22162897