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Sample records for bone tissue modeling

  1. Biomechanical Models and Experi ments in Bone Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Christian; ODDOU; Julien; PIERRE; Karim; OUDINA; Hervé; PETITE

    2005-01-01

    1 IntroductionThe understanding of the interactions between convective and diffusive phenomena of fluid dynamics origin, on the one side, associate reactive effects of biochemical nature, on the other, is a fundamental challenge and key problem in the context of bone tissue engineering. From the mastering of the complex biological phenomena related to the substrate degradation and remodelling of the extra cellular matrix that take place during the in vitro tissue culturing processes using cell seeded implan...

  2. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  3. Open forward and inverse problems in theoretical modeling of bone tissue adaptation.

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    Zadpoor, Amir Abbas

    2013-11-01

    Theoretical modeling of bone tissue adaptation started several decades ago. Many important problems have been addressed in this area of research during the last decades. However, many important questions remain unanswered. In this paper, an overview of open problems in theoretical modeling of bone tissue adaptation is presented. First, the principal elements of bone tissue adaptation models are defined and briefly reviewed. Based on these principal elements, four categories of open problems are identified. Two of these categories primarily include forward problems, while two others include inverse problems. In every one of the identified categories, important open problems are highlighted and their importance is discussed. It is shown that most of previous studies on the theoretical modeling of bone tissue adaptation have been focused on the problems of the first category and not much is done in three other categories. The paper tries to highlight these potentially important problems that have been so far largely overlooked and to inspire new avenues of research.

  4. Mechanical Stimulus Inhibits the Growth of a Bone Tissue Model Cultured In Vitro

    Institute of Scientific and Technical Information of China (English)

    Zong-ming Wan; Lu Liu; Jian-yu Li; Rui-xin Li; Yong Guo; Hao Li; Jian-ming Zhang; Xi-zheng Zhang

    2013-01-01

    Objectives To construct the cancellous bone explant model and a method of culturing these bone tissues in vitro, and to investigate the effect of mechanical load on growth of cancellous bone tissue in vitro. Methods Cancellous bone were extracted from rabbit femoral head and cut into 1-mm-thick and 8-mm-diameter slices under sterile conditions. HE staining and scanning electron microscopy were employed to identify the histomorphology of the model after being cultured with a new dynamic load and circulating perfusion bioreactor system for 0, 3, 5, and 7 days, respectively. We built a three-dimensional model using microCT and analyzed the loading effects using finite element analysis. The model was subjected to mechanical load of 1000, 2000, 3000, and 4000μεrespectively for 30 minutes per day. After 5 days of continuous stimuli, the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) were detected. Apoptosis was analyzed by DNA ladder detection and caspase-3/8/9 activity detection. Results After being cultured for 3, 5, and 7 days, the bone explant model grew well. HE staining showed the apparent nucleus in cells at the each indicated time, and electron microscope revealed the living cells in the bone tissue. The activities of AKP and TRAP in the bone explant model under mechanical load of 3000 and 4000μεwere significantly lower than those in the unstressed bone tissues (all P Conclusions The cancellous bone explant model extracted from the rabbit femoral head could be alive at least for 7 days in the dynamic load and circulating perfusion bioreactor system, however, pathological mechanical load could affect the bone tissue growth by apoptosis in vitro. The differentiation of osteoblasts and osteoclasts might be inhibited after the model is stimulated by mechanical load of 3000 and 4000με.

  5. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  6. Monte Carlo modeling of photon transport in buried bone tissue layer for quantitative Raman spectroscopy

    Science.gov (United States)

    Wilson, Robert H.; Dooley, Kathryn A.; Morris, Michael D.; Mycek, Mary-Ann

    2009-02-01

    Light-scattering spectroscopy has the potential to provide information about bone composition via a fiber-optic probe placed on the skin. In order to design efficient probes, one must understand the effect of all tissue layers on photon transport. To quantitatively understand the effect of overlying tissue layers on the detected bone Raman signal, a layered Monte Carlo model was modified for Raman scattering. The model incorporated the absorption and scattering properties of three overlying tissue layers (dermis, subdermis, muscle), as well as the underlying bone tissue. The attenuation of the collected bone Raman signal, predominantly due to elastic light scattering in the overlying tissue layers, affected the carbonate/phosphate (C/P) ratio by increasing the standard deviation of the computational result. Furthermore, the mean C/P ratio varied when the relative thicknesses of the layers were varied and the elastic scattering coefficient at the Raman scattering wavelength of carbonate was modeled to be different from that at the Raman scattering wavelength of phosphate. These results represent the first portion of a computational study designed to predict optimal probe geometry and help to analyze detected signal for Raman scattering experiments involving bone.

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

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    Dong Qingshan [Department of Oral and Maxillofacial Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070 (China); Shang Hongtao; Wu Wei [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Chen Fulin [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, Xi' an 710069 (China); Zhang Junrui [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Guo Jiaping [Department of Oral and Maxillofacial Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070 (China); Mao Tianqiu, E-mail: tianqiumao@126.com [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China)

    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. - Highlights: Black-Right-Pointing-Pointer A modified arteriovenous loop (AVL) model in rabbit was developed in this study. Black-Right-Pointing-Pointer Axial prevascularization was induced in a larger coral block by using the AVL. Black-Right-Pointing-Pointer The prefabrication of axial vascularized coral bone is superior as vascular carrier.

  8. A mathematical model for bone tissue regeneration inside a specific type of scaffold.

    Science.gov (United States)

    Sanz-Herrera, J A; Garcia-Aznar, J M; Doblare, M

    2008-10-01

    Bone tissue regeneration using scaffolds is receiving an increasing interest in orthopedic surgery and tissue engineering applications. In this study, we present the geometrical characterization of a specific family of scaffolds based on a face cubic centered (FCC) arrangement of empty pores leading to analytical formulae of porosity and specific surface. The effective behavior of those scaffolds, in terms of mechanical properties and permeability, is evaluated through the asymptotic homogenization theory applied to a representative volume element identified with the unit cell FCC. Bone growth into the scaffold is estimated by means of a phenomenological model that considers a macroscopic effective stress as the mechanical stimulus that regulates bone formation. Cell migration within the scaffold is modeled as a diffusion process based on Fick's law which allows us to estimate the cell invasion into the scaffold microstructure. The proposed model considers that bone growth velocity is proportional to the concentration of cells and regulated by the mechanical stimulus. This model allows us to explore what happens within the scaffold, the surrounding bone and their interaction. The mathematical model has been numerically implemented and qualitatively compared with previous experimental results found in the literature for a scaffold implanted in the femoral condyle of a rabbit. Specifically, the model predicts around 19 and 23% of bone regeneration for non-grafted and grafted scaffolds, respectively, both with an initial porosity of 76%.

  9. Long bone defect models for tissue engineering applications: criteria for choice.

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    Horner, Elizabeth A; Kirkham, Jennifer; Wood, David; Curran, Stephen; Smith, Mark; Thomson, Brian; Yang, Xuebin B

    2010-04-01

    The replacement and repair of bone lost due to trauma, cancer, or congenital defects is a major clinical challenge. Skeletal tissue engineering is a potentially powerful strategy in modern regenerative medicine, and research in this field has increased greatly in recent years. Tissue engineering strategies seek to translate research findings in the fields of materials science, stem cell biology, and biomineralization into clinical applications, demanding the use of appropriate in vivo models to investigate bone regeneration of the long bone. However, identification of the optimal in vivo segmental bone defect model from the literature is difficult due to the use of different animal species (large and small mammals), different bones (weight-bearing and nonweight bearing), and multiple protocols, including the use of various scaffolds, cells, and bioactives. The aim of this review is to summarize the available animal models for evaluating long bone regeneration in vivo. We highlight the differences not only in species and sites but also in defect size, means of defect creation, duration of study, and fixation method. A critical evaluation of the most clinically relevant models is addressed to guide the researcher in his/her choice of the most appropriate model to use in future hypothesis-driven investigations.

  10. Mathematical model for osteobstruction in bone regeneration mechanisms: a headway in skeletal tissue engineering.

    Science.gov (United States)

    Ogunsalu, C; Arunaye, F I; Ezeokoli, C; Gardner, M; Rohrer, M; Prasad, H

    2012-11-01

    In this paper, we formulate a mathematical model for the evaluation of parameters responsible for the retardation and eventual acceleration of bone regeneration on the contralateral side of the mandible of experimental animals, following the discovery of a new mechanism of bone regeneration called the osteobstruction mechanism (a negative mechanism of bone regeneration as opposed to the well established and extensively documented positive mechanisms such as osteogenesis, osteoinduction and osteoconduction). This osteobstructive mechanism was demonstrated by episodes of overtaking and reovertaking on single photon emission computed tomography (SPECT) following evaluation of osteoblastic activities in a sequential animal experiment to validate both the Ogunsalu sandwich technique (a double guided tissue technique; D-GTR) and the interceed membrane technique (a single guided tissue regeneration technique; S-GTR) utilizing SPECT, histological and histomorphometric evaluation. This work is now given special attention in terms of mathematical analysis because of limited experimental observations since experiments cannot be observed infinitely. Mathematical modelling is as such essential to generalize the results of this osteobstructive mechanism in bone regeneration. We utilize the Fisher's equation to describe bone cell mobilization during bone regeneration by two different techniques: the Ogunsalu sandwich bone regeneration technique (D-GTR) and the S-GTR.

  11. From stem cells to bone: phenotype acquisition, stabilization, and tissue engineering in animal models.

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    Gordeladze, Jan O; Reseland, Janne E; Duroux-Richard, Isabelle; Apparailly, Florence; Jorgensen, Christian

    2009-01-01

    The regeneration of bone tissue depends on the concerted actions of a plethora of signals that recruit mesenchymal stem cells for lineage-specific differentiation, with cellular phenotypes serving various functions throughout their life span. The signals are conveyed in hormones, growth factors, and mechanical forces, all of which ensure proper modeling and remodeling. Both processes are secured by indigenous and programmed metabolism in osteoblasts/osteocytes as well as in other stem cell (SC)-derived cell types (e.g., osteoclasts, bone lining cells) involved in the remodeling of the subject tissue. The focus of this review is the concerted action of these signals as well as the regulatory and/or stabilizing control circuits exhibited by a class of small RNAs, designated microRNAs. We discuss an in vitro approach for ensuring proper phenotype acquisition as well as the choice of scaffolds and animal models for in vivo tissue repair. This approach includes selection of SC niches to optimize bone formation in vivo, transcription factors important for osteoblastogenesis, the Wnt and Notch pathways of signaling, selection of delivery systems for gene therapy, use of appropriate matrices and scaffolds, in vivo mechanostimulation, choice of lesions to be repaired, and type of animal to use. We also discuss Wnt-related and SC-based treatment of osteoporosis. Throughout, we offer considerations for the selection of model systems and parameters to assess the entire procedure from initial SC selection to final bone repair, and conclude with a table summarizing our recommendations.

  12. Inter-dependent tissue growth and Turing patterning in a model for long bone development

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    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.

  13. Thermostability of bone tissue after immobilization induced osteopenia in a rat model.

    Directory of Open Access Journals (Sweden)

    Krzysztof Wójtowicz

    2008-12-01

    Full Text Available Immobilization of load-bearing bones results in imbalance of bone turnover followed by bone loss and impairment of its mechanical function. The question is whether immobilization induced bone loss is accompanied by deterioration of properties of the bone tissue components. Thermally induced transformations of collagen reflect the overall condition of the structure and cross-links in collagen network. The aim of the present study was to investigate whether immobilization induced osteopenia effects stability of collagen in bone tissue. Bone loss was developed by unilateral hindlimb immobilization in adult rats. Effects of unloading on cortical tissue from tibiae were studied after three weeks of unloading (I3R0 and four weeks after remobilization and free convalescence (I3R4 in both tibiae. Thermodynamic parameters of collagen degradation in bone were determined from differential scanning calorimetry (DSC analysis of partially dehydrated cortical bone samples from tibiae in the range of temperatures from 60 degrees C up to 300 degrees C. All bone samples were thermally very stable showing first clear endothermal process with a peak temperature within a range from 150 degrees C to 169 degrees C, for different samples. The next endotherm, wider and flatter, was observed between 245-298 degrees C with a peak at 255 degrees C - 260 degrees C. There were significant side-to-side (right to left differences for both endothermal processes in tibiae samples from experimental groups: I3R0 and I3R4. Immobilization of load-bearing bones influences stability of collagen in bone tissue. Free remobilization was not sufficient for recovery of thermal parameters of bone.

  14. Characterization of an ovine bilateral critical sized bone defect iliac wing model to examine treatment modalities based on bone tissue engineering.

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    Lansdowne, Jennifer L; Devine, Declan; Eberli, Ursula; Emans, Pieter; Welting, Tim J M; Odekerken, Jim C E; Schiuma, Damiano; Thalhauser, Martin; Bouré, Ludovic; Zeiter, Stephan

    2014-01-01

    Critical sized bone defect (CSBD) animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control) or filled with autologous corticocancellous bone graft (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.

  15. Characterization of an Ovine Bilateral Critical Sized Bone Defect Iliac Wing Model to Examine Treatment Modalities Based on Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Jennifer L. Lansdowne

    2014-01-01

    Full Text Available Critical sized bone defect (CSBD animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control or filled with autologous corticocancellous bone graft (clinical gold standard, positive control was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.

  16. Autologously generated tissue-engineered bone flaps for reconstruction of large mandibular defects in an ovine model.

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    Tatara, Alexander M; Kretlow, James D; Spicer, Patrick P; Lu, Steven; Lam, Johnny; Liu, Wei; Cao, Yilin; Liu, Guangpeng; Jackson, John D; Yoo, James J; Atala, Anthony; van den Beucken, Jeroen J J P; Jansen, John A; Kasper, F Kurtis; Ho, Tang; Demian, Nagi; Miller, Michael John; Wong, Mark E; Mikos, Antonios G

    2015-05-01

    The reconstruction of large craniofacial defects remains a significant clinical challenge. The complex geometry of facial bone and the lack of suitable donor tissue often hinders successful repair. One strategy to address both of these difficulties is the development of an in vivo bioreactor, where a tissue flap of suitable geometry can be orthotopically grown within the same patient requiring reconstruction. Our group has previously designed such an approach using tissue chambers filled with morcellized bone autograft as a scaffold to autologously generate tissue with a predefined geometry. However, this approach still required donor tissue for filling the tissue chamber. With the recent advances in biodegradable synthetic bone graft materials, it may be possible to minimize this donor tissue by replacing it with synthetic ceramic particles. In addition, these flaps have not previously been transferred to a mandibular defect. In this study, we demonstrate the feasibility of transferring an autologously generated tissue-engineered vascularized bone flap to a mandibular defect in an ovine model, using either morcellized autograft or synthetic bone graft as scaffold material.

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

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

    2016-08-31

    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.

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

    Science.gov (United States)

    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.

  19. Distribution Principle of Bone Tissue

    CERN Document Server

    Fan, Yifang; Fan, Yubo; Xu, Zongxiang; Li, Zhiyu

    2009-01-01

    Using the analytic and experimental techniques we present an exploratory study of the mass distribution features of the high coincidence of centre of mass of heterogeneous bone tissue in vivo and its centroid of geometry position. A geometric concept of the average distribution radius of bone issue is proposed and functional relation of this geometric distribution feature between the partition density and its relative tissue average distribution radius is observed. Based upon the mass distribution feature, our results suggest a relative distance assessment index between the center of mass of cortical bone and the bone center of mass and establish a bone strength equation. Analysing the data of human foot in vivo, we notice that the mass and geometric distribution laws have expanded the connotation of Wolff's law, which implies a leap towards the quantitative description of bone strength. We finally conclude that this will not only make a positive contribution to help assess osteoporosis, but will also provide...

  20. Validation of scaffold design optimization in bone tissue engineering: finite element modeling versus designed experiments.

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    Uth, Nicholas; Mueller, Jens; Smucker, Byran; Yousefi, Azizeh-Mitra

    2017-02-21

    This study reports the development of biological/synthetic scaffolds for bone tissue engineering (TE) via 3D bioplotting. These scaffolds were composed of poly(L-lactic-co-glycolic acid) (PLGA), type I collagen, and nano-hydroxyapatite (nHA) in an attempt to mimic the extracellular matrix of bone. The solvent used for processing the scaffolds was 1,1,1,3,3,3-hexafluoro-2-propanol. The produced scaffolds were characterized by scanning electron microscopy, microcomputed tomography, thermogravimetric analysis, and unconfined compression test. This study also sought to validate the use of finite-element optimization in COMSOL Multiphysics for scaffold design. Scaffold topology was simplified to three factors: nHA content, strand diameter, and strand spacing. These factors affect the ability of the scaffold to bear mechanical loads and how porous the structure can be. Twenty four scaffolds were constructed according to an I-optimal, split-plot designed experiment (DE) in order to generate experimental models of the factor-response relationships. Within the design region, the DE and COMSOL models agreed in their recommended optimal nHA (30%) and strand diameter (460 μm). However, the two methods disagreed by more than 30% in strand spacing (908 μm for DE; 601 μm for COMSOL). Seven scaffolds were 3D-bioplotted to validate the predictions of DE and COMSOL models (4.5-9.9 MPa measured moduli). The predictions for these scaffolds showed relative agreement for scaffold porosity (mean absolute percentage error of 4% for DE and 13% for COMSOL), but were substantially poorer for scaffold modulus (51% for DE; 21% for COMSOL), partly due to some simplifying assumptions made by the models. Expanding the design region in future experiments (e.g., higher nHA content and strand diameter), developing an efficient solvent evaporation method, and exerting a greater control over layer overlap could allow developing PLGA-nHA-collagen scaffolds to meet the mechanical requirements for

  1. Wrapped omentum with periosteum concurrent with adipose derived adult stem cells for bone tissue engineering in dog model.

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    Sadegh, Amin Bigham; Basiri, Ehsan; Oryan, Ahmad; Mirshokraei, Pezhman

    2014-03-01

    Adipose derived adult stem cells (ASCs) are multipotent cells that are able to differentiate into osteoblasts in presence of certain factors. The histological characteristics of periosteum makes it a specific tissue with a unique capacity to be engineered. Higher flexibility of the greater omentum is useful for reconstructive surgery. These criteria make it suitable for tissue engineering. The present study was designed to evaluate bone tissue engineering with periosteal free graft concurrent with ASCs and pedicle omentum in dog model. Twelve young female indigenous dogs were used in this experiment. In omental group (n = 4), end of omentum was wrapped by periosteum of the radial bone in abdomen of each dog. In omental-autogenously ASCs group (n = 4), 1 ml of ASCs was injected into the wrapped omentum with periosteum while in omental-allogenously ASCs group (n = 4), 1 ml of allogenous ASCs was injected. Lateral view radiographs were taken from the abdominal cavity postoperatively at the 2nd, 4th, 6th and 8th weeks post-surgery. Eight weeks after operation the dogs were re-anesthetized and the wrapped omenum by periosteum in all groups was found and removed for histopathological evaluation. Our results showed that omentum-periosteum, omental-periosteum-autogenous ASCs and omental-periosteum-allogenous ASCs groups demonstrated bone tissue formation in the abdominal cavity in dog model. The radiological, macroscopical and histological findings of the present study by the end of 8 weeks post-surgery indicate bone tissue engineering in all three groups in an equal level. The present study has shown that the wrapped omentum with periosteum concurrent with ASCs (autogenous or allogenous ASCs) lead to a favorable bone tissue formation. We suggested that it may be useful when pedicle graft omentum used concurrent with periosteum in the bone defect reconstruction, and this phenomenon should be studied in future.

  2. Prevascularized bone tissue engineering

    NARCIS (Netherlands)

    Rouwkema, Jeroen

    2007-01-01

    Tissue engineering has been an active field of research for several decades now. However, the number of successful clinical applications in the field of tissue engineering are limited and can mainly be found in thin or avascular tissues like skin and cartilage. One of the current limitations of tiss

  3. Bone tissue engineering: from bench to bedside

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    Maria A. Woodruff

    2012-10-01

    Full Text Available The drive to develop bone grafts for the filling of major gaps in the skeletal structure has led to a major research thrust towards developing biomaterials for bone engineering. Unfortunately, from a clinical perspective, the promise of bone tissue engineering which was so vibrant a decade ago has so far failed to deliver the anticipated results of becoming a routine therapeutic application in reconstructive surgery. Here we describe our bench to bedside concept, the first clinical results and a detailed analysis of long-term bone regeneration studies in preclinical animal models, exploiting methods of micro- and nano analysis of biodegradable composite scaffolds.

  4. Interactions between remodelling, architecture and tissue properties in cancellous bone

    OpenAIRE

    Linden, Jacqueline

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancellous bone. For this reason, the research presented in this thesis focussed on bone remodeling in cancellous bone. We used computer modeling, finite element calculations and in vivo labeled bone speci...

  5. Royal Jelly Prevents Osteoporosis in Rats: Beneficial Effects in Ovariectomy Model and in Bone Tissue Culture Model

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    Saburo Hidaka

    2006-01-01

    Full Text Available Royal jelly (RJ has been used worldwide for many years as medical products, health foods and cosmetics. Since RJ contains testosterone and has steroid hormone-type activities, we hypothesized that it may have beneficial effects on osteoporosis. We used both an ovariectomized rat model and a tissue culture model. Rats were divided into eight groups as follows: sham-operated (Sham, ovariectomized (OVX, OVX given 0.5% (w/w raw RJ, OVX given 2.0% (w/w RJ, OVX given 0.5% (w/w protease-treated RJ (pRJ, OVX given 2.0% (w/w pRJ, OVX given 17β-estradiol and OVX given its vehicle, respectively. The Ovariectomy decreased tibial bone mineral density (BMD by 24%. Administration of 17β-estradiol to OVX rats recovered the tibial BMD decrease by 100%. Administration of 2.0% (w/w RJ and 0.5–2.0% (w/w pRJ to OVX rats recovered it by 85% or more. These results indicate that both RJ and pRJ are almost as effective as 17β-estradiol in preventing the development of bone loss induced by ovariectomy in rats. In tissue culture models, both RJ and pRJ increased calcium contents in femoral-diaphyseal and femoral-metaphyseal tissue cultures obtained from normal male rats. However, in a mouse marrow culture model, they neither inhibited the parathyroid hormone (PTH-induced calcium loss nor affected the formation of osteoclast-like cells induced by PTH in mouse marrow culture system. Therefore, our results suggest that both RJ and pRJ may prevent osteoporosis by enhancing intestinal calcium absorption, but not by directly antagonizing the action of PTH.

  6. An intramembranous ossification model for the in silico analysis of bone tissue formation in tooth extraction sites.

    Science.gov (United States)

    Corredor-Gómez, Jennifer Paola; Rueda-Ramírez, Andrés Mauricio; Gamboa-Márquez, Miguel Alejandro; Torres-Rodríguez, Carolina; Cortés-Rodríguez, Carlos Julio

    2016-07-21

    The accurate modeling of biological processes allows us to predict the spatiotemporal behavior of living tissues by computer-aided (in silico) testing, a useful tool for the development of medical strategies, avoiding the expenses and potential ethical implications of in vivo experimentation. A model for bone healing in mouth would be useful for selecting proper surgical techniques in dental procedures. In this paper, the formulation and implementation of a model for Intramembranous Ossification is presented aiming to describe the complex process of bone tissue formation in tooth extraction sites. The model consists in a mathematical description of the mechanisms in which different types of cells interact, synthesize and degrade extracellular matrices under the influence of biochemical factors. Special attention is given to angiogenesis, oxygen-dependent effects and growth factor-induced apoptosis of fibroblasts. Furthermore, considering the depth-dependent vascularization of mandibular bone and its influence on bone healing, a functional description of the cell distribution on the severed periodontal ligament (PDL) is proposed. The developed model was implemented using the finite element method (FEM) and successfully validated by simulating an animal in vivo experiment on dogs reported in the literature. A good fit between model outcome and experimental data was obtained with a mean absolute error of 3.04%. The mathematical framework presented here may represent an important tool for the design of future in vitro and in vivo tests, as well as a precedent for future in silico studies on osseointegration and mechanobiology.

  7. A Quiescent, Regeneration-Responsive Tissue Engineered Mesenchymal Stem Cell Bone Marrow Niche Model via Magnetic Levitation.

    Science.gov (United States)

    Lewis, Emily Elizabeth Louise; Wheadon, Helen; Lewis, Natasha; Yang, Jingli; Mullin, Margaret; Hursthouse, Andrew; Stirling, David; Dalby, Matthew John; Berry, Catherine Cecilia

    2016-09-27

    The bone marrow niche represents a specialized environment that regulates mesenchymal stem cell quiescence and self-renewal, yet fosters stem cell migration and differentiation upon demand. An in vitro model that embodies these features would open up the ability to perform detailed study of stem cell behavior. In this paper we present a simple bone marrow-like niche model, which comprises of nanomagnetically levitated stem cells cultured as multicellular spheroids within a type I collagen gel. The stem cells maintained are nestin positive and remain quiescent until regenerative demand is placed upon them. In response to coculture wounding, they migrate and appropriately differentiate upon engraftment. This tissue engineered regeneration-responsive bone marrow-like niche model will allow for greater understanding of stem cell response to injury and also facilitate as a testing platform for drug candidates in a multiwell plate format.

  8. Collagen for bone tissue regeneration.

    Science.gov (United States)

    Ferreira, Ana Marina; Gentile, Piergiorgio; Chiono, Valeria; Ciardelli, Gianluca

    2012-09-01

    In the last decades, increased knowledge about the organization, structure and properties of collagen (particularly concerning interactions between cells and collagen-based materials) has inspired scientists and engineers to design innovative collagen-based biomaterials and to develop novel tissue-engineering products. The design of resorbable collagen-based medical implants requires understanding the tissue/organ anatomy and biological function as well as the role of collagen's physicochemical properties and structure in tissue/organ regeneration. Bone is a complex tissue that plays a critical role in diverse metabolic processes mediated by calcium delivery as well as in hematopoiesis whilst maintaining skeleton strength. A wide variety of collagen-based scaffolds have been proposed for different tissue engineering applications. These scaffolds are designed to promote a biological response, such as cell interaction, and to work as artificial biomimetic extracellular matrices that guide tissue regeneration. This paper critically reviews the current understanding of the complex hierarchical structure and properties of native collagen molecules, and describes the scientific challenge of manufacturing collagen-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of innovative techniques for scaffold and material manufacturing that are currently opening the way to the preparation of biomimetic substrates that modulate cell interaction for improved substitution, restoration, retention or enhancement of bone tissue function.

  9. Rapid maxillary expansion in alveolar cleft repaired with a tissue-engineered bone in a canine model.

    Science.gov (United States)

    Huang, Jialiang; Tian, Bo; Chu, Fengting; Yang, Chenjie; Zhao, Jun; Jiang, Xinquan; Qian, Yufen

    2015-08-01

    This study aims to investigate the effects of orthodontic expansion on graft area of a tissue-engineered bone (TEB) BMSCs/β-TCP, and to find an alternative strategy for the therapy of alveolar cleft. A unilateral alveolar cleft canine model was established and then treated with BMSCs/β-TCP under rapid maxillary expansion (RME). Sequential fluorescent labeling, radiography and helical computed tomography were used to evaluate new bone formation and mineralization in the graft area. Hematoxylin-eosin staining and Van Gieson׳s picro fuchsin staining were performed for histological and histomorphometric observation. ALP activity, mineralization and the expression of osteogenic differentiation related genes of BMSCs that grew on the β-TCP scaffold were promoted by their cultivation in osteogenic medium. Based on fact, TEB was constructed. After 8 weeks of treatment with BMSCs/β-TCP followed by RME, new bone formation and mineralization of the dogs were markedly accelerated, and bone resorption was significantly reduced, compared with the untreated dogs, or those only treated with autogenous iliac bone. The treatment with both TEB and RME evidently made the bone trabecula more abundant and the area of bone formation larger. What is more, there were no significant differences between BMSCs/β-TCP group and the group treated with autogenous bone and RME. This study further revealed that TEB was not only a feasible clinical approach for patients with alveolar cleft, but also a potential substituent of autogenous bone, and its combination with RME might be an alternative strategy for the therapy of alveolar cleft.

  10. The zebrafish as a model for tissue regeneration and bone remodelling

    NARCIS (Netherlands)

    Sharif, Faiza

    2011-01-01

    The aim of this thesis was to investigate the expression, and function of genes associated with remodelling and regeneration in the zebrafish model species. Here, we studied the role of cell populations, defined by their expression of markers, in bone regeneration and remodelling in zebrafish embryo

  11. The possibility of different CAD systems in the construction of mathematical model of bone tissue

    Directory of Open Access Journals (Sweden)

    Ivanov D.V.

    2013-09-01

    Full Text Available Modern methods of diagnosing of maxillary bones in various clinical situations presume a method of computer tomography. In some cases, the treatment planning according to three-dimensional image cannot be performed and the question of creation of the biomechanical model study area arises. Various methods of computer-aided design and three-dimensional modeling are worth while using to achieve the realization of the task.

  12. Nanotechnology in bone tissue engineering.

    Science.gov (United States)

    Walmsley, Graham G; McArdle, Adrian; Tevlin, Ruth; Momeni, Arash; Atashroo, David; Hu, Michael S; Feroze, Abdullah H; Wong, Victor W; Lorenz, Peter H; Longaker, Michael T; Wan, Derrick C

    2015-07-01

    Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  14. Microgravity Stress: Bone and Connective Tissue.

    Science.gov (United States)

    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.

  15. Tissue-engineered triphasic ceramic coated hydroxyapatite induced bone formation and vascularization at an extraskeletal site in a rat model

    Indian Academy of Sciences (India)

    Manitha B Nair; H K Varma; P V Mohanan; Annie John

    2011-12-01

    Tissue-engineered bone regeneration has attracted much attention because of its high clinical demand for restoration of injured tissues. In the present study, we have evaluated the capability of bare (without cells) and tissue-engineered (with osteogenic-induced rat Mesenchymal Stem Cells (MSCs)) bioactive ceramics such as hydroxyapatite (HA) and triphasic ceramic-coated hydroxyapatite (HASi) to mediate vascularisation and osteoinduction at an extraskeletal site of rat model. The viability, proliferation and osteogenic differentiation of MSCs on the scaffolds were assessed in vitro and thereby established the capability of HASi in providing a better structural habitat than HA. The vascular invasion was relatively low in bare and tissueengineered HA at 2 and 4 weeks. Interestingly, the implantation site was well vascularised with profuse ingrowth of blood capillaries in HASi groups, with preference for tissue-engineered HASi groups. Similarly, neo-osteogenesis studies were shown only by tissue-engineered HASi groups. The ingrowth of numerous osteoblast-like cells was seen around and within the pores of the material in bare HASi and tissue-engineered HASi groups (very low cellular infiltration in bare HA groups), but there was no osteoid deposition. The positive impact in forming bone in tissue-engineered HASi groups is attributable to the scaffold and to the cells, with the first choice for scaffold because both HA and HASi were engineered simultaneously with the cells from same source and same passage. Thus, highly porous interconnected porous structure and appropriate chemistry provided by HASi in combination with osteogenic-induced MSCs facilitated better vascularisation that lead to neo-osteogenesis.

  16. Soft tissue aneurysmal bone cyst

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.L.; Gielen, J.L.; Delrue, F.; De Schepper, A.M.A. [Department of Radiology, Universitair Ziekenhuis Antwerpen (University of Antwerp), Wilrijkstraat 10, 2650, Edegem (Belgium); Salgado, R. [Department of Pathology, Universitair Ziekenhuis Antwerpen (University of Antwerp), Wilrijkstraat 10, 2650, Edegem (Belgium)

    2004-08-01

    A soft tissue aneurysmal bone cyst located in the right gluteus medius of a 21-year-old man is reported. On conventional radiography, the lesion demonstrated a spherically trabeculated mass with a calcific rim. On CT scan, it showed a well-organized peripheral calcification resembling a myositis ossificans. On MRI, it presented as a multilocular, cystic lesion with fluid-fluid levels. The lesion had no solid components except for intralesional septa. Although findings on imaging and histology were identical to those described in classical aneurysmal bone cyst, diagnosis was delayed because of lack of knowledge of this entity and its resemblance to the more familiar post-traumatic heterotopic ossification (myositis ossificans). (orig.)

  17. Sequential Fluorescent Labeling Observation of Maxillary Sinus Augmentation by a Tissue-engineered Bone Complex in Canine Model

    Institute of Scientific and Technical Information of China (English)

    Xin-quan Jiang; Shao-yi Wang; Jun Zhao; Xiu-li Zhang; Zhi-yuan Zhang

    2009-01-01

    Aim To evaluate the effects of maxillary sinus floor elevation by a tissue-engineered bone complex of β-tricalcium phosphate (β-TCP) and autologous osteoblasts in dogs. Methodology Autologous osteoblasts from adult Beagle dogs were cultured in vitro. They were further combined with β-TCP to construct the tissue-engineered bone complex. 12 cases of maxillary sinus floor elevation surgery were made bilaterally in 6 animals and randomly repaired with the following 3 groups of materials: Group A (osteoblasts/β-TCP); Group B (β-TCP); Group C (autogenous bone) (n-4 per group). A polychrome sequential fluorescent labeling was performed post-operatively and the animals were sacrificed 24 weeks after operation for histological observation.Results Our results showed that autologous osteoblasts were successfully expanded and the osteoblastic phenoltypes were confirmed by ALP and Alizarin red staining. The cells could attach and proliferate well on the surface of the β-TCP scaffold. The fluorescent and histological observation showed that the tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than β-TCP along or even autologous bone. It had also maximally maintained the elevated sinus height than both control groups. Conclusion Porous β-TCP has served as a good scaffold for autologous osteoblasts seeding. The tissue-engineered bone complex with β-TCP and autologous osteoblasts might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation.

  18. Mechanistic, mathematical model to predict the dynamics of tissue genesis in bone defects via mechanical feedback and mediation of biochemical factors.

    Directory of Open Access Journals (Sweden)

    Shannon R Moore

    2014-06-01

    Full Text Available The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial and trends (temporal of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based

  19. Effect of higher frequency components and duration of vibration on bone tissue alterations in the rat-tail model.

    Science.gov (United States)

    Peelukhana, Srikara V; Goenka, Shilpi; Kim, Brian; Kim, Jay; Bhattacharya, Amit; Stringer, Keith F; Banerjee, Rupak K

    2015-01-01

    To formulate more accurate guidelines for musculoskeletal disorders (MSD) linked to Hand-Arm Vibration Syndrome (HAVS), delineation of the response of bone tissue under different frequencies and duration of vibration needs elucidation. Rat-tails were vibrated at 125 Hz (9 rats) and 250 Hz (9 rats), at 49 m/s(2), for 1D (6 rats), 5D (6 rats) and 20D (6 rats); D=days (4 h/d). Rats in the control group (6 rats for the vibration groups; 2 each for 1D, 5D, and 20D) were left in their cages, without being subjected to any vibration. Structural and biochemical damages were quantified using empty lacunae count and nitrotyrosine signal-intensity, respectively. One-way repeated-measure mixed-model ANOVA at pbone, structural damage quantified through empty lacunae count was significant (pbone while the trabecular bone showed significant (pbone tissue are dependent upon higher vibration frequencies of 125 Hz, 250 Hz and the duration of vibration (5D, 20D).

  20. Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

    Science.gov (United States)

    Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

    2004-07-01

    Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

  1. Geometric and mechanical properties evaluation of scaffolds for bone tissue applications designing by a reaction-diffusion models and manufactured with a material jetting system

    Directory of Open Access Journals (Sweden)

    Marco A. Velasco

    2016-10-01

    Full Text Available Scaffolds are essential in bone tissue engineering, as they provide support to cells and growth factors necessary to regenerate tissue. In addition, they meet the mechanical function of the bone while it regenerates. Currently, the multiple methods for designing and manufacturing scaffolds are based on regular structures from a unit cell that repeats in a given domain. However, these methods do not resemble the actual structure of the trabecular bone which may work against osseous tissue regeneration. To explore the design of porous structures with similar mechanical properties to native bone, a geometric generation scheme from a reaction-diffusion model and its manufacturing via a material jetting system is proposed. This article presents the methodology used, the geometric characteristics and the modulus of elasticity of the scaffolds designed and manufactured. The method proposed shows its potential to generate structures that allow to control the basic scaffold properties for bone tissue engineering such as the width of the channels and porosity. The mechanical properties of our scaffolds are similar to trabecular tissue present in vertebrae and tibia bones. Tests on the manufactured scaffolds show that it is necessary to consider the orientation of the object relative to the printing system because the channel geometry, mechanical properties and roughness are heavily influenced by the position of the surface analyzed with respect to the printing axis. A possible line for future work may be the establishment of a set of guidelines to consider the effects of manufacturing processes in designing stages.

  2. Effect of the Intermittent Hypoxia on the Bone Tissue State After Microgravitation Modeling

    Science.gov (United States)

    Berezovskiy, V. A.; Litovka, I. G.; Chaka, H. G.; Magomedov, S.; Mehed, N. V.

    The authors studied the influence of low PO2 under normal atmospheric pressure on the Ca and P metabolism, bone remodeling markers, and biomechanical properties of the femura bone in rats with their hind limbs unloaded. A hypoxic gas mixture (HGM) was given in intermittent regime A and B for 8 hours/day during 28 days. It was shown that regime A slows down the development of osteopenia and may be used in complex with other rehabilitation procedures for preventing the unloading osteopenia.

  3. Bone Tissue Engineering: Recent Advances and Challenges

    Science.gov (United States)

    Amini, Ami R.; Laurencin, Cato T.; Nukavarapu, Syam P.

    2013-01-01

    The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field. PMID:23339648

  4. Rapid prototyping technology and its application in bone tissue engineering.

    Science.gov (United States)

    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.

  5. Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering

    Science.gov (United States)

    Velasco, Marco A.; Narváez-Tovar, Carlos A.; Garzón-Alvarado, Diego A.

    2015-01-01

    A review about design, manufacture, and mechanobiology of biodegradable scaffolds for bone tissue engineering is given. First, fundamental aspects about bone tissue engineering and considerations related to scaffold design are established. Second, issues related to scaffold biomaterials and manufacturing processes are discussed. Finally, mechanobiology of bone tissue and computational models developed for simulating how bone healing occurs inside a scaffold are described. PMID:25883972

  6. Design, materials, and mechanobiology of biodegradable scaffolds for bone tissue engineering.

    Science.gov (United States)

    Velasco, Marco A; Narváez-Tovar, Carlos A; Garzón-Alvarado, Diego A

    2015-01-01

    A review about design, manufacture, and mechanobiology of biodegradable scaffolds for bone tissue engineering is given. First, fundamental aspects about bone tissue engineering and considerations related to scaffold design are established. Second, issues related to scaffold biomaterials and manufacturing processes are discussed. Finally, mechanobiology of bone tissue and computational models developed for simulating how bone healing occurs inside a scaffold are described.

  7. The Design and Use of Animal Models for Translational Research in Bone Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    2010-01-07

    repair,40,41 evaluation of the differential effects of marrow-derived and periosteal - derived cell populations,42 and in screening for the effects of cell...defect or gap in bone (caused by either tissue loss or distraction maintained by internal or external fixation), local tissue loss (particularly periosteal ...as an excel- lent resource. Critical defects are defined as ‘‘a defect that will not heal without intervention.’’ The femur and tibial diaphysis tend

  8. Autologously generated tissue-engineered bone flaps for reconstruction of large mandibular defects in an ovine model.

    NARCIS (Netherlands)

    Tatara, A.M.; Kretlow, J.D.; Spicer, P.P.; Lu, S.; Lam, J.; Liu, W.; Cao, Y.; Liu, G.; Jackson, J.D.; Yoo, J.J.; Atala, A.; Beucken, J.J.J.P van den; Jansen, J.A.; Kasper, F.K.; Ho, T.; Demian, N.; Miller, M.J.; Wong, M.E.; Mikos, A.G.

    2015-01-01

    The reconstruction of large craniofacial defects remains a significant clinical challenge. The complex geometry of facial bone and the lack of suitable donor tissue often hinders successful repair. One strategy to address both of these difficulties is the development of an in vivo bioreactor, where

  9. Autologously generated tissue-engineered bone flaps for reconstruction of large mandibular defects in an ovine model.

    NARCIS (Netherlands)

    Tatara, A.M.; Kretlow, J.D.; Spicer, P.P.; Lu, S.; Lam, J.; Liu, W.; Cao, Y.; Liu, G.; Jackson, J.D.; Yoo, J.J.; Atala, A.; Beucken, J.J.J.P van den; Jansen, J.A.; Kasper, F.K.; Ho, T.; Demian, N.; Miller, M.J.; Wong, M.E.; Mikos, A.G.

    2015-01-01

    The reconstruction of large craniofacial defects remains a significant clinical challenge. The complex geometry of facial bone and the lack of suitable donor tissue often hinders successful repair. One strategy to address both of these difficulties is the development of an in vivo bioreactor, where

  10. Stem cells in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jeong Min [Department of Preventive and Social Dentistry and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik [Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Mantalaris, Anathathios, E-mail: yshwang@khu.ac.k [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

    2010-12-15

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  11. Towards improved scaffolds for bone tissue engineering

    NARCIS (Netherlands)

    Nandakumar, A.

    2012-01-01

    Tissue engineering aims to restore, maintain or improve tissue function of damaged tissues. In a classical set-up, a scaffold functions as a supporting structure and a carrier for growth factors and/or cells. Human mesenchymal stromal cells (hMSCs) have the ability to differentiate into bone, cartil

  12. Nanostructured scaffolds for bone tissue engineering.

    Science.gov (United States)

    Li, Xiaoming; Wang, Lu; Fan, Yubo; Feng, Qingling; Cui, Fu-Zhai; Watari, Fumio

    2013-08-01

    It has been demonstrated that nanostructured materials, compared with conventional materials, may promote greater amounts of specific protein interactions, thereby more efficiently stimulating new bone formation. It has also been indicated that, when features or ingredients of scaffolds are nanoscaled, a variety of interactions can be stimulated at the cellular level. Some of those interactions induce favorable cellular functions while others may leads to toxicity. This review presents the mechanism of interactions between nanoscaled materials and cells and focuses on the current research status of nanostructured scaffolds for bone tissue engineering. Firstly, the main requirements for bone tissue engineering scaffolds were discussed. Then, the mechanism by which nanoscaled 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. Copyright © 2013 Wiley Periodicals, Inc.

  13. The materials used in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Tereshchenko, V. P., E-mail: tervp@ngs.ru; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M. [Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk (Russian Federation)

    2015-11-17

    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  14. Powder-based 3D printing for bone tissue engineering.

    Science.gov (United States)

    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.

  15. Orthopaedic tissue engineering and bone regeneration.

    Science.gov (United States)

    Dickson, Glenn; Buchanan, Fraser; Marsh, David; Harkin-Jones, Eileen; Little, Uel; McCaigue, Mervyn

    2007-01-01

    Orthopaedic tissue engineering combines the application of scaffold materials, cells and the release of growth factors. It has been described as the science of persuading the body to reconstitute or repair tissues that have failed to regenerate or heal spontaneously. In the case of bone regeneration 3-D scaffolds are used as a framework to guide tissue regeneration. Mesenchymal cells obtained from the patient via biopsy are grown on biomaterials in vitro and then implanted at a desired site in the patient's body. Medical implants that encourage natural tissue regeneration are generally considered more desirable than metallic implants that may need to be removed by subsequent intervention. Numerous polymeric materials, from natural and artificial sources, are under investigation as substitutes for skeletal elements such as cartilage and bone. For bone regeneration, cells (obtained mainly from bone marrow aspirate or as primary cell outgrowths from bone biopsies) can be combined with biodegradable polymeric materials and/or ceramics and absorbed growth factors so that osteoinduction is facilitated together with osteoconduction; through the creation of bioactive rather than bioinert scaffold constructs. Relatively rapid biodegradation enables advantageous filling with natural tissue while loss of polymer strength before mass is disadvantageous. Innovative solutions are required to address this and other issues such as the biocompatibility of material surfaces and the use of appropriate scaffold topography and porosity to influence bone cell gene expression.

  16. Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

    Directory of Open Access Journals (Sweden)

    Bressan Eriberto

    2012-01-01

    Full Text Available 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.

  17. Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model.

    Science.gov (United States)

    Luangphakdy, Viviane; Boehm, Cynthia; Pan, Hui; Herrick, James; Zaveri, Phil; Muschler, George F

    2016-01-01

    Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods achieve a bone

  18. Marginal bone and soft tissue behavior following platform switching abutment connection/disconnection--a dog model study.

    Science.gov (United States)

    Alves, Célia C; Muñoz, Fernando; Cantalapiedra, António; Ramos, Isabel; Neves, Manuel; Blanco, Juan

    2015-09-01

    The effect on the marginal peri-implant tissues following repeated platform switching abutment removal and subsequent reconnection was studied. Six adult female Beagle dogs were selected, and Pm3 and Pm4 teeth, both left and right sides, were extracted and the sites healed for 3 months. At this time, 24 bone level (BL) (Straumann, Basel, Switzerland) Ø 3.3/8 mm implants were placed, 2 in each side on Pm3 and Pm4 regions. In one side (control group), 12 bone level conical Ø 3.6 mm healing abutments and, on the other side (test group), 12 Narrow CrossFit (NC) multibase abutments (Straumann) , Basel, Switzerland) were connected at time of implant surgery. On test group, all prosthetic procedures were carried out direct to multibase abutment without disconnecting it, where in the control group, the multibase abutment was connected/disconnected five times (at 6/8/10/12/14 weeks) during prosthetic procedures. Twelve fixed metal bridges were delivered 14 weeks after implant placement. A cleaning/control appointment was scheduled 6 months after implant placement. The animals were sacrificed at 9 months of the study. Clinical parameters and peri-apical x-rays were registered in every visit. Histomorphometric analysis was carried out for the 24 implants. The distance from multibase abutment shoulder to the first bone implant contact (S-BIC) was defined as the primary histomorphometric parameter. Wilcoxon comparison paired test (n = 6) found no statistically significant differences (buccal P = 0.917; Lingual P = 0.463) between test and control groups both lingually and buccally for S-BIC distance. Only Pm3 buccal aBE-BC (distance from the apical end of the barrier epithelium to the first bone implant contact) (P = 0.046) parameter presented statistically significant differences between test and control groups. Control group presented 0.57 mm more recession than test group, being this difference statistically significant between the two groups (P < 0.001). It can be conclude

  19. Biomechanical study of the bone tissue with dental implants interaction

    Directory of Open Access Journals (Sweden)

    Navrátil P.

    2011-12-01

    Full Text Available The article deals with the stress-strain analysis of human mandible in the physiological state and after the dental implant application. The evaluation is focused on assessing of the cancellous bone tissue modeling-level. Three cancellous bone model-types are assessed: Non-trabecular model with homogenous isotropic material, nontrabecular model with inhomogeneous material obtained from computer tomography data using CT Data Analysis software, and trabecular model built from mandible section image. Computational modeling was chosen as the most suitable solution method and the solution on two-dimensional level was carried out. The results show that strain is more preferable value than stress in case of evaluation of mechanical response in cancellous bone. The non-trabecular model with CT-obtained material model is not acceptable for stress-strain analysis of the cancellous bone for singularities occurring on interfaces of regions with different values of modulus of elasticity.

  20. Bone tissue engineering using 3D printing

    Directory of Open Access Journals (Sweden)

    Susmita Bose

    2013-12-01

    Full Text Available With the advent of additive manufacturing technologies in the mid 1980s, many applications benefited from the faster processing of products without the need for specific tooling or dies. However, the application of such techniques in the area of biomedical devices has been slow due to the stringent performance criteria and concerns related to reproducibility and part quality, when new technologies are in their infancy. However, the use of additive manufacturing technologies in bone tissue engineering has been growing in recent years. Among the different technology options, three dimensional printing (3DP is becoming popular due to the ability to directly print porous scaffolds with designed shape, controlled chemistry and interconnected porosity. Some of these inorganic scaffolds are biodegradable and have proven ideal for bone tissue engineering, sometimes even with site specific growth factor/drug delivery abilities. This review article focuses on recent advances in 3D printed bone tissue engineering scaffolds along with current challenges and future directions.

  1. Interactions between muscle tissues and bone metabolism.

    Science.gov (United States)

    Kawao, Naoyuki; Kaji, Hiroshi

    2015-05-01

    Sarcopenia and osteoporosis have recently been noted for their relationship with locomotive syndrome and increased number of older people. Sarcopenia is defined by decreased muscle mass and impaired muscle function, which may be associated with frailty. Several clinical data have indicated that increased muscle mass is related to increased bone mass and reduced fracture risk. Genetic, endocrine and mechanical factors as well as inflammatory and nutritional states concurrently affect muscle tissues and bone metabolism. Several genes, including myostatin and α-actinin 3, have been shown in a genome-wide association study (GWAS) to be associated with both sarcopenia and osteoporosis. Vitamin D, growth hormone and testosterone as well as pathological disorders, such as an excess in glucocorticoid and diabetes, affect both muscle and bone. Basic and clinical research of bone metabolism and muscle biology suggests that bone interacts with skeletal muscle via signaling from local and humoral factors in addition to their musculoskeletal function. However, the physiological and pathological mechanisms related to muscle and bone interactions remain unclear. We found that Tmem119 may play a critical role in the commitment of myoprogenitor cells to the osteoblast lineage. We also reported that osteoglycin and FAM5C might be muscle-derived humoral osteogenic factors. Other factors, including myostatin, osteonectin, insulin-like growth factor I, irisin and osteocalcin, may be associated with the interactions between muscle tissues and bone metabolism. © 2014 Wiley Periodicals, Inc.

  2. Silk fibroin membrane used for guided bone tissue regeneration.

    Science.gov (United States)

    Cai, Yurong; Guo, Junmao; Chen, Cen; Yao, Chenxue; Chung, Sung-Min; Yao, Juming; Lee, In-Seop; Kong, Xiangdong

    2017-01-01

    With the aim to develop a novel membrane with an appropriate mechanical property and degradation rate for guided bone tissue regeneration, lyophilized and densified silk fibroin membrane was fabricated and its mechanical behavior as well as biodegradation property were investigated. The osteoconductive potency of the silk fibroin membranes were evaluated in a defect rabbit calvarial model. Silk fibroin membrane showed the modulated biodegradable and mechanical properties via ethanol treatment with different concentration. The membrane could prevent soft tissue invasion from normal tissue healing, and the amounts of new bone and defect closure with silk fibroin membrane were similar to those of commercially available collagen membrane.

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

    Science.gov (United States)

    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.].

  4. Localized tissue mineralization regulated by bone remodelling: A computational approach

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  6. Computational modeling of adherent cell growth in a hollow-fiber membrane bioreactor for large-scale 3-D bone tissue engineering.

    Science.gov (United States)

    Mohebbi-Kalhori, Davod; Behzadmehr, Amin; Doillon, Charles J; Hadjizadeh, Afra

    2012-09-01

    The use of hollow-fiber membrane bioreactors (HFMBs) has been proposed for three-dimensional bone tissue growth at the clinical scale. However, to achieve an efficient HFMB design, the relationship between cell growth and environmental conditions must be determined. Therefore, in this work, a dynamic double-porous media model was developed to determine nutrient-dependent cell growth for bone tissue formation in a HFMB. The whole hollow-fiber scaffold within the bioreactor was treated as a porous domain in this model. The domain consisted of two interpenetrating porous regions, including a porous lumen region available for fluid flow and a porous extracapillary space filled with a collagen gel that contained adherent cells for promoting long-term growth into tissue-like mass. The governing equations were solved numerically and the model was validated using previously published experimental results. The contributions of several bioreactor design and process parameters to the performance of the bioreactor were studied. The results demonstrated that the process and design parameters of the HFMB significantly affect nutrient transport and thus cell behavior over a long period of culture. The approach presented here can be applied to any cell type and used to develop tissue engineering hollow-fiber scaffolds.

  7. The effect of bone displacement operations on facial soft tissues.

    Science.gov (United States)

    Habib, Ali; Hisham, Ahmed

    2013-01-01

    A novel biomechanical model for face soft tissue (skin, mucosa, and muscles) is introduced to investigate the effect of mandible and chin bone displacement on the overall appearance of the patient's face. Nonlinear FE analysis is applied to the model and the results obtained are used to help surgeons to decide the amount of displacement required.

  8. Porphyromonas gingivalis infection-induced tissue and bone transcriptional profiles.

    Science.gov (United States)

    Meka, A; Bakthavatchalu, V; Sathishkumar, S; Lopez, M C; Verma, R K; Wallet, S M; Bhattacharyya, I; Boyce, B F; Handfield, M; Lamont, R J; Baker, H V; Ebersole, J L; Kesavalu, L

    2010-02-01

    Porphyromonas gingivalis has been associated with subgingival biofilms in adult periodontitis. However, the molecular mechanisms of its contribution to chronic gingival inflammation and loss of periodontal structural integrity remain unclear. This investigation aimed to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. P. gingivalis FDC 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and was analysed for transcript profiles using Murine GeneChip((R)) arrays to provide a molecular profile of the events that occur following infection of these tissues. After P. gingivalis infection, 6452 and 2341 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P tissues and calvarial bone included cell adhesion (immune system) molecules, Toll-like receptors, B-cell receptor signaling, transforming growth factor-beta cytokine family receptor signaling, and major histocompatibility complex class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T-cell stimulation, and downregulation of antiviral and T-cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption. This is the first in vivo evidence that localized P. gingivalis infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed soft tissues and calvarial bone.

  9. Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

    Science.gov (United States)

    Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

    2016-01-01

    The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Bone tissue engineering for spine fusion : An experimental study on ectopic and orthotopic implants in rats

    NARCIS (Netherlands)

    van Gaalen, SM; Dhert, WJA; van den Muysenberg, A; Oner, FC; van Blitterswijk, C; Verbout, AJ; de Bruijn, J.D.

    2004-01-01

    Alternatives to the use of autologous bone as a bone graft in spine surgery are needed. The purpose of this study was to examine tissue-engineered bone constructs in comparison with control scaffolds without cells in a posterior spinal implantation model in rats. Syngeneic bone marrow cells were cul

  11. Composite Scaffolds for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Min Wang

    2006-01-01

    Full Text Available Biomaterial and scaffold development underpins the advancement of tissue engineering. Traditional scaffolds based on biodegradable polymers such as poly(lactic acid and poly(lactic acid-co-glycolic acid are weak and non-osteoconductive. For bone tissue engineering, polymer-based composite scaffolds containing bioceramics such as hydroxyapatite can be produced and used. The bioceramics can be either incorporated in the scaffolds as a dispersed secondary phase or form a thin coating on the pore surface of polymer scaffolds. This bioceramic phase renders the scaffolds bioactive and also strengthens the scaffolds. There are a number of methods that can be used to produce bioceramic-polymer composite scaffolds. This paper gives an overview of our efforts in developing composite scaffolds for bone tissue engineering.

  12. Bioresorbable and nonresorbable polymers for bone tissue engineering.

    Science.gov (United States)

    Girones Molera, Jordi; Mendez, José Alberto; San Roman, Julio

    2012-01-01

    In recent years, bone tissue engineering has emerged as one of the main research areas in the field of regenerative biomedicine. Frequency and relevance age-related diseases, such as healing and regeneration of bone tissues, are rising due to increasing life expectancy. Even though bone tissue has excellent self-regeneration ability, when bone defects exceed a critical size, impaired bone formation can occur and surgical intervention becomes mandatory. Bone tissue engineering represents an alternative approach to conventional bone transplants. The main aim of tissue engineering is to repair, regenerate or reconstruct damaged or degenerative tissue. This review presents an overview on the main materials, techniques and strategies in the field of bone tissue engineering. Whilst presenting some reviews recently published that deepen on each of the sections of the paper, this review article aims to present some of the most relevant advances, both in terms of new materials and strategies, currently being developed for bone repair and regeneration.

  13. A new zebrafish bone crush injury model

    Directory of Open Access Journals (Sweden)

    Sara Sousa

    2012-07-01

    While mammals have a limited capacity to repair bone fractures, zebrafish can completely regenerate amputated bony fin rays. Fin regeneration in teleosts has been studied after partial amputation of the caudal fin, which is not ideal to model human bone fractures because it involves substantial tissue removal, rather than local tissue injury. In this work, we have established a bone crush injury model in zebrafish adult caudal fin, which consists of the precise crush of bony rays with no tissue amputation. Comparing these two injury models, we show that the initial stages of injury response are the same regarding the activation of wound healing molecular markers. However, in the crush assay the expression of the blastema marker msxb appears later than during regeneration after amputation. Following the same trend, bone cells deposition and expression of genes involved in skeletogenesis are also delayed. We further show that bone and blood vessel patterning is also affected. Moreover, analysis of osteopontin and Tenascin-C reveals that they are expressed at later stages in crushed tissue, suggesting that in this case bone repair is prolonged for longer than in the case of regeneration after amputation. Due to the nature of the trauma inflicted, the crush injury model seems more similar to fracture bone repair in mammals than bony ray amputation. Therefore, the new model that we present here may help to identify the key processes that regulate bone fracture and contribute to improve bone repair in humans.

  14. [Scaffold-based Bone Tissue Engineering].

    Science.gov (United States)

    Holzapfel, B M; Rudert, M; Hutmacher, D W

    2017-08-01

    Tissue engineering provides the possibility of regenerating damaged or lost osseous structures without the need for permanent implants. Within this context, biodegradable and bioresorbable scaffolds can provide structural and biomechanical stability until the body's own tissue can take over their function. Additive biomanufacturing makes it possible to design the scaffold's architectural characteristics to specifically guide tissue formation and regeneration. Its nano-, micro-, and macro-architectural properties can be tailored to ensure vascularization, oxygenation, nutrient supply, waste exchange, and eventually ossification not only in its periphery but also in its center, which is not in direct contact with osteogenic elements of the surrounding healthy tissue. In this article we provide an overview about our conceptual design and process of the clinical translation of scaffold-based bone tissue engineering applications.

  15. Building bone tissue: matrices and scaffolds in physiology and biotechnology

    Directory of Open Access Journals (Sweden)

    Riminucci M.

    2003-01-01

    Full Text Available Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies.

  16. Alginate based scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Valente, J.F.A.; Valente, T.A.M. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Alves, P.; Ferreira, P. [CIEPQPF, Departamento de Engenharia Quimica, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Silva, A. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2012-12-01

    The design and production of scaffolds for bone tissue regeneration is yet unable to completely reproduce the native bone properties. In the present study new alginate microparticle and microfiber aggregated scaffolds were produced to be applied in this area of regenerative medicine. The scaffolds' mechanical properties were characterized by thermo mechanical assays. Their morphological characteristics were evaluated by isothermal nitrogen adsorption and scanning electron microscopy. The density of both types of scaffolds was determined by helium pycnometry and mercury intrusion porosimetry. Furthermore, scaffolds' cytotoxic profiles were evaluated in vitro by seeding human osteoblast cells in their presence. The results obtained showed that scaffolds have good mechanical and morphological properties compatible with their application as bone substitutes. Moreover, scaffold's biocompatibility was confirmed by the observation of cell adhesion and proliferation after 5 days of being seeded in their presence and by non-radioactive assays. - Highlights: Black-Right-Pointing-Pointer Design and production of scaffolds for bone tissue regeneration. Black-Right-Pointing-Pointer Microparticle and microfiber alginate scaffolds were produced through a particle aggregation technique; Black-Right-Pointing-Pointer Scaffolds' mechanically and biologically properties were characterized through in vitro studies;.

  17. Nanostructured Mesoporous Silicas for Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Isabel Izquierdo-Barba

    2008-01-01

    Full Text Available The research on the development of new biomaterials that promote bone tissue regeneration is receiving great interest by the biomedical scientific community. Recent advances in nanotechnology have allowed the design of materials with nanostructure similar to that of natural bone. These materials can promote new bone formation by inducing the formation of nanocrystalline apatites analogous to the mineral phase of natural bone onto their surfaces, i.e. they are bioactive. They also stimulate osteoblast proliferation and differentiation and, therefore, accelerate the healing processes. Silica-based ordered mesoporous materials are excellent candidates to be used as third generation bioceramics that enable the adsorption and local control release of biological active agents that promote bone regeneration. This local delivery capability together with the bioactive behavior of mesoporous silicas opens up promising expectations in the bioclinical field. In this review, the last advances in nanochemistry aimed at designing and tailoring the chemical and textural properties of mesoporous silicas for biomedical applications are described. The recent developed strategies to synthesize bioactive glasses with ordered mesopore arrangements are also summarized. Finally, a deep discussion about the influence of the textural parameters and organic modification of mesoporous silicas on molecules adsorption and controlled release is performed.

  18. Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

    Science.gov (United States)

    Rodionova, Natalia

    Investigations on the space biosatellites has shown that the bone skeleton is one of the most im-portant targets of the effect space flight factors on the organism. Bone tissue cells were studied by electron microscopy in biosamples of rats' long bones flown on the board american station "SLS-2" and in experiments with modelling of microgravity ("tail suspension" method) with using autoradiography. The analysis of data permits to suppose that the processes of remod-eling in bone tissue at microgravity include the following succession of cell-to-cell interactions. Osteocytes as mechanosensory cells are first who respond to a changing "mechanical field". The next stage is intensification of osteolytic processes in osteocytes, leading to a volume en-largement of the osteocytic lacunae and removal of the "excess bone". Then mechanical signals have been transmitted through a system of canals and processes of the osteocytic syncitium to certain superficial bone zones and are perceived by osteoblasts and bone-lining cells (superficial osteocytes), as well as by the bone-marrow stromal cells. The sensitivity of stromal cells, pre-osteoblasts and osteoblasts, under microgravity was shown in a number of works. As a response to microgravity, the system of stromal cells -preosteoblasts -osteoblasts displays retardation of proliferation, differentiation and specific functions of osteogenetic cells. This is supported by the 3H-thymidine studies of the dynamics of differentiation of osteogenetic cells in remodeling zones. But unloading is not adequate and in part of the osteocytes are apoptotic changes as shown by our electron microscopic investigations. An osteocytic apoptosis can play the role in attraction the osteoclasts and in regulation of bone remodeling. The apoptotic bodies with a liquid flow through a system of canals are transferred to the bone surface, where they fulfil the role of haemoattractants for monocytes come here and form osteoclasts. The osteoclasts destroy

  19. Immunotherapy for Bone and Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Takenori Uehara

    2015-01-01

    Full Text Available Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE, an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.

  20. Muscle and bone, two interconnected tissues.

    Science.gov (United States)

    Tagliaferri, Camille; Wittrant, Yohann; Davicco, Marie-Jeanne; Walrand, Stéphane; Coxam, Véronique

    2015-05-01

    As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone-muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Pullulan microcarriers for bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Aydogdu, Hazal [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Keskin, Dilek [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Middle East Technical University, Department of Engineering Sciences, Ankara 06800 (Turkey); METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey); Baran, Erkan Turker, E-mail: erkanturkerbaran@gmail.com [METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey); Tezcaner, Aysen, E-mail: tezcaner@metu.edu.tr [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Middle East Technical University, Department of Engineering Sciences, Ankara 06800 (Turkey); METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey)

    2016-06-01

    Microcarrier systems offer a convenient way to repair bone defects as injectable cell carriers that can be applied with small incisions owing to their small size and spherical shape. In this study, pullulan (PULL) microspheres were fabricated and characterized as cell carriers for bone tissue engineering applications. PULL was cross-linked by trisodium trimetaphosphate (STMP) to enhance the stability of the microspheres. Improved cytocompatibility was achieved by silk fibroin (SF) coating and biomimetic mineralization on the surface by incubating in simulated body fluid (SBF). X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescent microscopy analysis confirmed biomimetic mineralization and SF coating on microspheres. The degradation analysis revealed that PULL microspheres had a slow degradation rate with 8% degradation in two weeks period indicating that the microspheres would support the formation of new bone tissue. Furthermore, the mechanical tests showed that the microspheres had a high mechanical stability that was significantly enhanced with the biomimetic mineralization. In vitro cell culture studies with SaOs-2 cells showed that cell viability was higher on SF and SBF coated microspheres on 7th day compared to PULL ones under dynamic conditions. Alkaline phosphatase activity was higher for SF coated microspheres in comparison to uncoated microspheres when dynamic culture condition was applied. The results suggest that both organic and inorganic surface modifications can be applied on PULL microspheres to prepare a biocompatible microcarrier system with suitable properties for bone tissue engineering. - Highlights: • Porous PULL microspheres were prepared as cell carrier for the first time. • Mineralization on the microspheres improved their mechanical properties. • Mineralization and SF coating enhanced cell proliferation on PULL microspheres.

  2. Quantitative polarized Raman spectroscopy in highly turbid bone tissue

    Science.gov (United States)

    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 (p0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

  3. Effects of radiotherapy on bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Samantha Seara da; Almeida, Darcy de [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil)]. E-mail: samanthaseara@hotmail.com; Sarmento, Viviane Almeida; Ramalho, Luciana Maria Pedreira; Freitas, Andre Carlos de [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil). Faculdade de Odontologia; Tavares, Maria Eulina; Souza, Jailton Caetano [Hospital Santa Izabel (HSI), Salvador, BA (Brazil); Veeck, Elaine Bauer; Costa, Nilza Pereira da [Pontificia Univ. Catolica do Rio Grande do Sul (PUCRS), Porto Alegre, RS (Brazil)

    2007-05-15

    Objective: To investigate the effects of radiotherapy on bone tissues and the accuracy of gray level measurements on radiographic images. Materials and methods: Four Wistar rats were submitted to external radiotherapy (single 3000 cGy dose) on an area of 2 cm x 2 cm of their right legs. The animals were sacrificed six weeks after radiotherapy, and both irradiated and contralateral (non-irradiated) legs were removed, dissected, evaluated for thickness, x-rayed in a standardized form and histologically processed (stained with hematoxylin-eosin and picrosirius red). The radiographs were digitalized and the gray level average was measured with the ImageTool{sup R} software. Results: The femur thickness of non-irradiated legs was greater than that of the irradiated legs (p < 0.05). Radiographically, the findings indicated a higher bone density in the non-irradiated legs, although with no statistically significant difference (p > 0.05). Histological analysis of the irradiated legs demonstrated a decrease in the number of osteocytes and Haversian canals, although with no statistically significance (p > 0.05). On the other hand, a significant increase in adipocytes was observed, resulting in a reduction of medullary tissue in the irradiated legs (p < 0.05), besides a higher osteoblastic activity in the non-irradiated legs (p < 0.05). Conclusion: Radiotherapy within the above mentioned parameters determined a decrease in activity of bone remodeling, which could be radiographically detected in the majority of the evaluated specimens. (author)

  4. Influence of USP laser radiation on cell morphology: HaCat and MG-63 cell lines for bone and soft tissue modelling in dentistry

    Science.gov (United States)

    Meister, Joerg; Schelle, Florian; Beier, Imke; Bourauel, Christoph; Frentzen, Matthias; Kraus, Dominik

    Due to the high intensities of USP laser radiation, the interaction with matter is always attended with a plasma formation. Therefore the surrounding tissue can be influenced by heat generation and additional light emission from the UV up to the near and mid infrared. In dentistry it is of importance that the treatment of bone and soft tissues, i.e. oral mucosa, with a USP laser should not cause any kind of morphological changes on the cell level leading to a delayed wound healing or cell mutation. HaCaT keratinocyte cells were used for epidermal (soft tissue) and MG-63 osteoblast-like cells for hard tissue (bone) modelling. Cell growing was realized on glas cover slips. Irradiation was carried out with a USP Nd:YVO4 laser having a center wavelength at 1064 nm. Based on the pulse duration of 8 ps and a pulse repetition rate of 500 kHz the laser emits an average power of 9 W. For efficiency testing of cell removal on glas cover slips, 1, 5, 25, 50 and 75 repetitions of the scanning pattern (scan loops) were used. Heat distribution during laser irradiation was measured with an infrared camera system. Subsequently haematoxylin staining and SEM investigations were used to analyse the morphological changes. Differences of cell removal efficiency were observed with repetitions =50 were cell-free. Additionally, repetitions >=25 showed side effects for both cell lines. Cell destruction in both cell lines could be verified using the haematoxylin staining and the SEM pictures.

  5. Effect of bone-soft tissue friction on ultrasound axial shear strain elastography

    Science.gov (United States)

    Tang, Songyuan; Chaudhry, Anuj; Kim, Namhee; Reddy, J. N.; Righetti, Raffaella

    2017-08-01

    Bone-soft tissue friction is an important factor affecting several musculoskeletal disorders, frictional syndromes and the ability of a bone fracture to heal. However, this parameter is difficult to determine using non-invasive imaging modalities, especially in clinical settings. Ultrasound axial shear strain elastography is a non-invasive imaging modality that has been used in the recent past to estimate the bonding between different tissue layers. As most elastography methods, axial shear strain elastography is primarily used in soft tissues. More recently, this technique has been proposed to assess the bone-soft tissue interface. In this paper, we investigate the effect of a variation in bone-soft tissue friction coefficient in the resulting axial shear strain elastograms. Finite element poroelastic models of bone specimens exhibiting different bone-soft tissue friction coefficients were created and mechanically analyzed. These models were then imported to an ultrasound elastography simulation module to assess the presence of axial shear strain patterns. In vitro experiments were performed to corroborate selected simulation results. The results of this study show that the normalized axial shear strain estimated at the bone-soft tissue interface is statistically correlated to the bone-soft tissue coefficient of friction. This information may prove useful to better interpret ultrasound elastography results obtained in bone-related applications and, possibly, monitor bone healing.

  6. Experimental research on plasma destruction of bone tissue

    Directory of Open Access Journals (Sweden)

    Vdovin O.V.

    2012-06-01

    Full Text Available The main condition in achieving a favorable outcome is surgical treatment of patients with tumor-like diseases and benign bone tumors erosion of neoplasm within the healthy tissues. To reduce the number of recurrences the various chemical and physical methods on resection areas have been performed. The authors have proposed a new method of low temperature plasma treatment of bone tissue with the temperature of 20000°C. Exposing the plasma flow on bone tissue leads to loss of all cellular elements including neoplastic elements with preservation of the mineral bone structure. The direct correlation between the capacity of the plasma flow and intensity of bone destruction has been defined. This allows a differentiated use of plasma destruction in skeletal bones according to anatomy, size and type of bone tissue (spongy or cortical as well as patient's individual condition of the tissue

  7. Imaging of alkaline phosphatase activity in bone tissue.

    Directory of Open Access Journals (Sweden)

    Terence P Gade

    Full Text Available The purpose of this study was to develop a paradigm for quantitative molecular imaging of bone cell activity. We hypothesized the feasibility of non-invasive imaging of the osteoblast enzyme alkaline phosphatase (ALP using a small imaging molecule in combination with (19Flourine magnetic resonance spectroscopic imaging ((19FMRSI. 6, 8-difluoro-4-methylumbelliferyl phosphate (DiFMUP, a fluorinated ALP substrate that is activatable to a fluorescent hydrolysis product was utilized as a prototype small imaging molecule. The molecular structure of DiFMUP includes two Fluorine atoms adjacent to a phosphate group allowing it and its hydrolysis product to be distinguished using (19Fluorine magnetic resonance spectroscopy ((19FMRS and (19FMRSI. ALP-mediated hydrolysis of DiFMUP was tested on osteoblastic cells and bone tissue, using serial measurements of fluorescence activity. Extracellular activation of DiFMUP on ALP-positive mouse bone precursor cells was observed. Concurringly, DiFMUP was also activated on bone derived from rat tibia. Marked inhibition of the cell and tissue activation of DiFMUP was detected after the addition of the ALP inhibitor levamisole. (19FMRS and (19FMRSI were applied for the non-invasive measurement of DiFMUP hydrolysis. (19FMRS revealed a two-peak spectrum representing DiFMUP with an associated chemical shift for the hydrolysis product. Activation of DiFMUP by ALP yielded a characteristic pharmacokinetic profile, which was quantifiable using non-localized (19FMRS and enabled the development of a pharmacokinetic model of ALP activity. Application of (19FMRSI facilitated anatomically accurate, non-invasive imaging of ALP concentration and activity in rat bone. Thus, (19FMRSI represents a promising approach for the quantitative imaging of bone cell activity during bone formation with potential for both preclinical and clinical applications.

  8. Mechanotransduction by bone cells in vitro: mechanobiology of bone tissue

    NARCIS (Netherlands)

    Mullender, M.; El Haj, A.J.; Yang, Y.; van Duin, M.A.; Burger, E.H.; Klein-Nulend, J.

    2004-01-01

    Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the load profile and whether different components, such

  9. Printing bone : the application of 3D fiber deposition for bone tissue engineering

    NARCIS (Netherlands)

    Fedorovich, N.E.

    2011-01-01

    Bone chips are used by orthopaedic surgeons for treating spinal trauma and to augment large bone defects. A potential alternative to autologous bone is regeneration of bone tissue in the lab by developing hybrid implants consisting of osteogenic (stem) cells seeded on supportive matrices.

  10. Printing bone : the application of 3D fiber deposition for bone tissue engineering

    NARCIS (Netherlands)

    Fedorovich, N.E.

    2011-01-01

    Bone chips are used by orthopaedic surgeons for treating spinal trauma and to augment large bone defects. A potential alternative to autologous bone is regeneration of bone tissue in the lab by developing hybrid implants consisting of osteogenic (stem) cells seeded on supportive matrices. Applicatio

  11. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

    Science.gov (United States)

    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  12. IL-5 drives eosinophils from bone marrow to blood and tissues in a guinea-pig model of visceral larva migrans syndrome

    Directory of Open Access Journals (Sweden)

    L. H. Faccioli

    1996-01-01

    Full Text Available This study was undertaken to evaluate the role of IL-5 in eosinophil migration and in the maintenance of eosinophilia in a guinea-pig model of visceral larva migrans syndrome. The results show that the infection of animals with Toxocara canis induced an early increase in serum IL-5 levels that might be essential for eosinophil differentiation and proliferation and for the development of eosinophilia. When infected guinea-pigs were treated with mAb anti-IL-5 (TRFK-5 given at the same time or 1 or 3 days after infection, there was a high percentage of reduction of eosinophil counts 18 days after infection. However, when the mAb was administered during the peak of eosinophilia, there was high inhibition in blood, no inhibition in bronchoalveolar lavage fluid (BALF or peritoneum and an increase in eosinophil numbers in bone marrow. Thus, a basic level of IL-5 may be essential to drive eosinophils from bone marrow to blood and tissues, and for the maintenance of eosinophilia in infected animals. We may also conclude that when eosinophils have already migrated to the lungs, TRFK-5 has no power to inhibit eosinophilia, which is also under control of local lung cells producing IL-5. In this way, only one later TRFK-5 treatment may not be sufficient to modify the lung parenchyma microenvironment, since T. canis antigens had already stimulated some cell populations to produce IL-5.

  13. Natural Polymer-Cell Bioconstructs for Bone Tissue Engineering.

    Science.gov (United States)

    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.

  14. Biodegradable Polymers in Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Leon E. Govaert

    2009-07-01

    Full Text Available The use ofdegradable polymers in medicine largely started around the mid 20th century with their initial use as in vivo resorbing sutures. Thorough knowledge on this topic as been gained since then and the potential applications for these polymers were, and still are, rapidly expanding. After improving the properties of lactic acid-based polymers, these were no longer studied only from a scientific point of view, but also for their use in bone surgery in the 1990s. Unfortunately, after implanting these polymers, different foreign body reactions ranging from the presence of white blood cells to sterile sinuses with resorption of the original tissue were observed. This led to the misconception that degradable polymers would, in all cases, lead to inflammation and/or osteolysis at the implantation site. Nowadays, we have accumulated substantial knowledge on the issue of biocompatibility of biodegradable polymers and are able to tailor these polymers for specific applications and thereby strongly reduce the occurrence of adverse tissue reactions. However, the major issue of biofunctionality, when mechanical adaptation is taken into account, has hitherto been largely unrecognized. A thorough understanding of how to improve the biofunctionality, comprising biomechanical stability, but also visualization and sterilization of the material, together with the avoidance of fibrotic tissue formation and foreign body reactions, may greatly enhance the applicability and safety of degradable polymers in a wide area of tissue engineering applications. This review will address our current understanding of these biofunctionality factors, and will subsequently discuss the pitfalls remaining and potential solutions to solve these problems.

  15. Engineering bone tissue substitutes from human induced pluripotent stem cells

    National Research Council Canada - National Science Library

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

    2013-01-01

    ...) 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...

  16. The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

    Science.gov (United States)

    Bhattacharya, Indranil; Ghayor, Chafik; Weber, Franz E.

    2016-01-01

    2500 years ago, Hippocrates realized that bone can heal without scaring. The natural healing potential of bone is, however, restricted to small defects. Extended bone defects caused by trauma or during tumor resections still pose a huge problem in orthopedics and cranio-maxillofacial surgery. Bone tissue engineering strategies using stem cells, growth factors, and scaffolds could overcome the problems with the treatment of extended bone defects. In this review, we give a short overview on bone tissue engineering with emphasis on the use of adipose tissue-derived stem cells and small molecules.

  17. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  18. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  19. Non-viral gene therapy for bone tissue engineering

    NARCIS (Netherlands)

    Wegman, F.

    2013-01-01

    In bone tissue engineering bone morphogentic protein-2 (BMP-2) is one of the most commonly used growth factors. It induces stem cells to differentiate into the osteogenic lineage to form new bone. Clinically however, high dosages of protein are administered due to fast degradation, which is associat

  20. Residual stress in bone structure and tissue of rabbit's tibiofibula.

    Science.gov (United States)

    Tadano, Shigeru; Okoshi, Taro

    2006-01-01

    This paper presents an X-ray diffraction method of measuring the residual stress/strain in bone tissue of rabbit's tibia. To derive the residual stress, bone powder of the diameter less than 40 micrometers was used as a control specimen at non-stressed state. From the X-ray measurements, it was clear that the distribution of residual stress existed in the bone tissue. The tensile residual stress at bone axial direction occurred in the proximal-medial region of rabbit's tibia. The compressive stress occurred in the other regions. In addition, the mechanism to generate the residual stress was investigated by sequential cutting of the tibiofibula system from bone structure scale to bone tissue scale. The remodeling is a phenomenon that the bone structure adapts functionally to mechanical environment. The residual stress will become a mechanical trigger to induce the remodeling.

  1. A nano-hydroxyapatite--pullulan/dextran polysaccharide composite macroporous material for bone tissue engineering.

    Science.gov (United States)

    Fricain, Jean Christophe; Schlaubitz, Silke; Le Visage, Catherine; Arnault, Isabelle; Derkaoui, Sidi Mohammed; Siadous, Robin; Catros, Sylvain; Lalande, Charlotte; Bareille, Reine; Renard, Martine; Fabre, Thierry; Cornet, Sandro; Durand, Marlène; Léonard, Alain; Sahraoui, Nouredine; Letourneur, Didier; Amédée, Joëlle

    2013-04-01

    Research in bone tissue engineering is focused on the development of alternatives to allogenic and autologous bone grafts that can stimulate bone healing. Here, we present scaffolds composed of the natural hydrophilic polysaccharides pullulan and dextran, supplemented or not with nanocrystalline hydroxyapatite particles (nHA). In vitro studies revealed that these matrices induced the formation of multicellular aggregates and expression of early and late bone specific markers with human bone marrow stromal cells in medium deprived of osteoinductive factors. In absence of any seeded cells, heterotopic implantation in mice and goat, revealed that only the composite macroporous scaffold (Matrix + nHA) (i) retained subcutaneously local growth factors, including Bone Morphogenetic Protein 2 (BMP2) and VEGF165, (ii) induced the deposition of a biological apatite layer, (iii) favored the formation of a dense mineralized tissue subcutaneously in mice, as well osteoid tissue after intramuscular implantation in goat. The composite scaffold was thereafter implanted in orthotopic preclinical models of critical size defects, in small and large animals, in three different bony sites, i.e. the femoral condyle of rat, a transversal mandibular defect and a tibial osteotomy in goat. The Matrix + nHA induced a highly mineralized tissue in the three models whatever the site of implantation, as well as osteoid tissue and bone tissue regeneration in direct contact to the matrix. We therefore propose this composite matrix as a material for stimulating bone cell differentiation of host mesenchymal stem cells and bone formation for orthopedic and maxillofacial surgical applications.

  2. A bioreactor system for clinically relevant bone tissue engineering

    NARCIS (Netherlands)

    Janssen, Franciscus Wilhelmus

    2010-01-01

    Tissue engineering of bone by combining mesenchymal stem cells (MSCs) with a suitable ceramic carrier provides a potential alternative for autologous bone grafts. However, for large scale-production, the current two dimensional (2D) multiplication process in tissue culture flasks has some serious dr

  3. Micromechanical finite-element modeling and experimental characterization of the compressive mechanical properties of polycaprolactone-hydroxyapatite composite scaffolds prepared by selective laser sintering for bone tissue engineering.

    Science.gov (United States)

    Eshraghi, Shaun; Das, Suman

    2012-08-01

    Bioresorbable scaffolds with mechanical properties suitable for bone tissue engineering were fabricated from polycaprolactone (PCL) and hydroxyapatite (HA) by selective laser sintering (SLS) and modeled by finite-element analysis (FEA). Both solid gage parts and scaffolds having 1-D, 2-D and 3-D orthogonal, periodic porous architectures were made with 0, 10, 20 and 30 vol.% HA. PCL:HA scaffolds manufactured by SLS had nearly full density (99%) in the designed solid regions and had excellent geometric and dimensional control. Through optimization of the SLS process, the compressive moduli for our solid gage parts and scaffolds are the highest reported in the literature for additive manufacturing. The compressive moduli of solid gage parts were 299.3, 311.2, 415.5 and 498.3 MPa for PCL:HA loading at 100:0, 90:10, 80:20 and 70:30, respectively. The compressive effective stiffness tended to increase as the loading of HA was increased and the designed porosity was lowered. In the case of the most 3-D porous scaffold, the compressive modulus more than doubled from 14.9 to 36.2 MPa when changing the material from 100:0 to 70:30 PCL:HA. A micromechanical FEA model was developed to investigate the reinforcement effect of HA loading on the compressive modulus of the bulk material. Using a first-principles based approach, the random distribution of HA particles in a solidified PCL matrix was modeled for any HA loading to predict the bulk mechanical properties of the composites. The bulk mechanical properties were also used for FEA of the scaffold geometries. The results of the FEA were found to be in good agreement with experimental mechanical testing. The development of patient- and site-specific composite tissue-engineering constructs with tailored properties can be seen as a direct extension of this work on computational design, a priori modeling of mechanical properties and direct digital manufacturing.

  4. Sinusoidal electromagnetic fields promote bone formation and inhibit bone resorption in rat femoral tissues in vitro.

    Science.gov (United States)

    Zhou, Jian; Ma, Xiao-Ni; Gao, Yu-Hai; Yan, Juan-Li; Shi, Wen-Gui; Xian, Cory J; Chen, Ke-Ming

    2016-01-01

    Effects of sinusoidal electromagnetic fields (SEMFs) on bone metabolism have not yet been well defined. The present study investigated SEMF effects on bone formation and resorption in rat femur bone tissues in vitro. Cultured femur diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues were treated with 50 Hz 1.8 mT SEMFs 1.5 h per day for up to 12 days and treatment effects on bone formation and resorption markers and associated gene expression were examined. Treatment with SEMFs caused a significant increase in alkaline phosphatase (ALP) activity and inhibited the tartrate-resistant acid phosphatase (TRACP) activity in the femoral diaphyseal or metaphyseal tissues. SEMFs also significantly increased levels of mRNA expression of osterix (OSX), insulin-like growth factor (IGF-1) and ALP in the bone tissues. SEMF treatment decreased glucose content and increased lactic acid contents in the culture conditioned medium. In addition, treatment with SEMFs decreased mRNA expression levels of bone resorption-related genes TRACP, macrophage colony stimulating factor (M-CSF) and cathepsin K (CTSK) in the cultured bone tissues. In conclusion, the current study demonstrated that treatment with 1.8 mT SEMFs at 1.5 h per day promoted bone formation, increased metabolism and inhibited resorption in both metaphyseal and diaphyseal bone tissues in vitro.

  5. Nanomaterial N-CP/DLPLG as potent1onal tissue graft in osteoreparation in combination with bone marrow cells on subcutaneous implantation model

    Directory of Open Access Journals (Sweden)

    Janićijević Jelena M.

    2008-01-01

    Full Text Available The need for bone graft materials in osteoreparation is tremendous. Many researches have shown that calcium-phosphate bioceramics have good biocompatibility and osteoconductivity. We used nanocomposite biomaterial calcium phosphate coated with poly (dl-lactide-co-glycolide or N-CP/DLPLG. The goal of this investigation was to examine weather N-CP/DLPLG has ability to sustain growth of bone marrow cells after subcutaneous implantation in Balb/c mice. For that purpose N-CP/DLPLG implants with and without bone marrow cells (control were made. Implants were extracted after eight days and eight weeks. In implants loaded with bone marrow cells after eight days and eight weeks we observed fields rich in cells, angiogenesis and collagen genesis. These results showed that N-CP/DLPLG has property of tissue scaffold which sustain bone marrow cells growth and collagen production. This represents a good way for further examination of N-CP/DLPLG as potentional tissue scaffold in osteoreparation.

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

    Directory of Open Access Journals (Sweden)

    Maira L. Mendonça

    Full Text Available 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.

  7. Injectable hydrogels for cartilage and bone tissue engineering

    Science.gov (United States)

    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

  8. Impact of P2RX7 ablation on the morphological, mechanical and tissue properties of bones in a murine model of duchenne muscular dystrophy.

    Science.gov (United States)

    Mohamad, N S; Sinadinos, A; Górecki, D C; Zioupos, P; Tong, J

    2016-10-03

    Duchenne muscular dystrophy (DMD) is an inherited, lethal disorder characterised by progressive muscle degeneration and associated bone abnormalities. We have previously demonstrated that P2RX7 purinergic receptors contribute to the pathogenesis of DMD, and found that P2RX7 ablation alleviated the severity of the disease. In this work we have used a dystrophic mdx mouse crossed with the global P2RX7 receptor to generate a knockout mouse (mdx/P2X7(-)(/)(-)), and compared its morphometric, mechanical and tissue properties against those of mdx, as well as the wild type (WT) and the P2RX7 knockout (P2X7(-)(/)(-)). Micro-computed tomography (µCT), three-point bending testing, scanning electron microscopy (SEM) and nano-indentation were utilised in the study. The bones were analysed at approximately 4 weeks of age to examine the impact of P2RX7 ablation on the bone properties during the acute disease phase, before muscle wasting is fully developed. The results show that P2RX7 purinoceptor ablation has produced improvement or significant improvement in some of the morphological, the mechanical and the tissue properties of the dystrophic bones examined. Specifically, although the ablation produced smaller bones with significantly lower total cross-section area (Tt.Ar) and Second Moment of Area (SMA), significantly higher cortical bone area (Ct.Ar), cortical area fraction (Ct.Ar/Tt.Ar) and trabecular bone volume fraction (BV/TV) are found in the mdx/P2X7(-/-) mice than in any other types. Further, the mdx/P2X7(-)(/)(-) bones have relatively higher average flexural strength, work-to-fracture and significantly higher strain to failure compared with those of mdx, suggesting greater resistance to fracture. Indentation modulus, elasticity and creep are also significantly improved in the knockout cortical bones over those of mdx. These findings seem to suggest that specific pharmacological blockade of P2RX7 may improve dystrophic bones, with a potential for therapeutic

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

    Science.gov (United States)

    Harsanyl, L

    1977-02-01

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

  10. Inducible models of bone loss.

    Science.gov (United States)

    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

    Bone is an essential organ that not only confers structural stability to the organism, but also serves as a reservoir for hematopoietic elements and is thought to affect systemic homeostasis through the release of endocrine factors as well as calcium. The loss of bone mass due to an uncoupling of bone formation and bone resorption leads to increased fragility that can result in devastating fractures. Further understanding of the effects of environmental stimuli on the development of bone disease in humans is needed, and they can be studied using animal models. Here, we present established and novel methods for the induction of bone loss in mice, including manipulation of diet and environment, administration of drugs, irradiation, and surgically induced hormone deficiency. All of these models are directly related to human cases, and thus, can be used to investigate the causes of bone loss resulting from these interventions. Copyright © 2014 John Wiley & Sons, Inc.

  11. Quantitative plutonium microdistribution in bone tissue of vertebra from a Mayak worker.

    Science.gov (United States)

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

    2010-10-01

    The purpose of this study 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, the quantitative relationships 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 humans as well as other cases with different exposure patterns and types of plutonium.

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

    Science.gov (United States)

    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.

  13. A new biological approach to guided bone and tissue regeneration.

    Science.gov (United States)

    Montanari, Marco; Callea, Michele; Yavuz, Izzet; Maglione, Michele

    2013-04-09

    The purpose of this study was to determine the potential of platelet-rich fibrin (PRF) membranes used for guided bone and tissue regeneration. A patient with insufficient alveolar ridge width in aesthetic zone was enrolled. The patient's blood was centrifuged to obtain PRF membranes. Autogenous bone graft was mixed with bovine hydroxyapatite, PRF particles and applied to fill the defect. Five PRF membranes were placed over the bone mix. After 4 months a cone-beam CT was performed to evaluate bone regeneration. The use of PRF as cover membrane permitted a rapid epithelisation and represented an effective barrier versus epithelial cell penetration. After 4 months the site appeared precociously healed and the bone volume increased. This new approach represents a predictable method of augmenting deficient alveolar ridges. Guided bone regeneration with PRF showed limitation compared with guided bone regeneration using collagen membrane in terms of bone gain. The association of collagen membrane and PRF could be a good association.

  14. Nanomechanical mapping of bone tissue regenerated by magnetic scaffolds.

    Science.gov (United States)

    Bianchi, Michele; Boi, Marco; Sartori, Maria; Giavaresi, Gianluca; Lopomo, Nicola; Fini, Milena; Dediu, Alek; Tampieri, Anna; Marcacci, Maurilio; Russo, Alessandro

    2015-01-01

    Nanoindentation can provide new insights on the maturity stage of regenerating bone. The aim of the present study was the evaluation of the nanomechanical properties of newly-formed bone tissue at 4 weeks from the implantation of permanent magnets and magnetic scaffolds in the trabecular bone of rabbit femoral condyles. Three different groups have been investigated: MAG-A (NdFeB magnet + apatite/collagen scaffold with magnetic nanoparticles directly nucleated on the collagen fibers during scaffold synthesis); MAG-B (NdFeB magnet + apatite/collagen scaffold later infiltrated with magnetic nanoparticles) and MAG (NdFeB magnet). The mechanical properties of different-maturity bone tissues, i.e. newly-formed immature, newly-formed mature and native trabecular bone have been evaluated for the three groups. Contingent correlations between elastic modulus and hardness of immature, mature and native bone have been examined and discussed, as well as the efficacy of the adopted regeneration method in terms of "mechanical gap" between newly-formed and native bone tissue. The results showed that MAG-B group provided regenerated bone tissue with mechanical properties closer to that of native bone compared to MAG-A or MAG groups after 4 weeks from implantation. Further, whereas the mechanical properties of newly-formed immature and mature bone were found to be fairly good correlated, no correlation was detected between immature or mature bone and native bone. The reported results evidence the efficacy of nanoindentation tests for the investigation of the maturity of newly-formed bone not accessible through conventional analyses.

  15. Alginate composites for bone tissue engineering: a review.

    Science.gov (United States)

    Venkatesan, Jayachandran; Bhatnagar, Ira; Manivasagan, Panchanathan; Kang, Kyong-Hwa; Kim, Se-Kwon

    2015-01-01

    Bone is a complex and hierarchical tissue consisting of nano hydroxyapatite and collagen as major portion. Several attempts have been made to prepare the artificial bone so as to replace the autograft and allograft treatment. Tissue engineering is a promising approach to solve the several issues and is also useful in the construction of artificial bone with materials including polymer, ceramics, metals, cells and growth factors. Composites consisting of polymer-ceramics, best mimic the natural functions of bone. Alginate, an anionic polymer owing enormous biomedical applications, is gaining importance particularly in bone tissue engineering due to its biocompatibility and gel forming properties. Several composites such as alginate-polymer (PLGA, PEG and chitosan), alginate-protein (collagen and gelatin), alginate-ceramic, alginate-bioglass, alginate-biosilica, alginate-bone morphogenetic protein-2 and RGD peptides composite have been investigated till date. These alginate composites show enhanced biochemical significance in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, alkaline phosphatase increase, excellent mineralization and osteogenic differentiation. Hence, alginate based composite biomaterials will be promising for bone tissue regeneration. This review will provide a broad overview of alginate preparation and its applications towards bone tissue engineering.

  16. Chitosan Composites for Bone Tissue Engineering—An Overview

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2010-08-01

    Full Text Available Bone contains considerable amounts of minerals and proteins. Hydroxyapatite [Ca10(PO46(OH2] is one of the most stable forms of calcium phosphate and it occurs in bones as major component (60 to 65%, along with other materials including collagen, chondroitin sulfate, keratin sulfate and lipids. In recent years, significant progress has been made in organ transplantation, surgical reconstruction and the use of artificial protheses to treat the loss or failure of an organ or bone tissue. Chitosan has played a major role in bone tissue engineering over the last two decades, being a natural polymer obtained from chitin, which forms a major component of crustacean exoskeleton. In recent years, considerable attention has been given to chitosan composite materials and their applications in the field of bone tissue engineering due to its minimal foreign body reactions, an intrinsic antibacterial nature, biocompatibility, biodegradability, and the ability to be molded into various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. The composite of chitosan including hydroxyapatite is very popular because of the biodegradability and biocompatibility in nature. Recently, grafted chitosan natural polymer with carbon nanotubes has been incorporated to increase the mechanical strength of these composites. Chitosan composites are thus emerging as potential materials for artificial bone and bone regeneration in tissue engineering. Herein, the preparation, mechanical properties, chemical interactions and in vitro activity of chitosan composites for bone tissue engineering will be discussed.

  17. Transplantation of bone marrow stromal cells overexpressing human vascular endothelial growth factor 165 enhances tissue repair in a rat model of radiation-induced injury

    Institute of Scientific and Technical Information of China (English)

    Wang Tao; Liao Tian'an; Wang Hong; Deng Wei; Yu Dahai

    2014-01-01

    Background The multilineage differentiation potential ability of bone marrow stromal cells (BMSCs) showed great potential in tissue engineering,while vascular endothelial growth factor 165 (VEGF165) promotes vasculogenesis and further promotes tissue regeneration.This study aimed to assess the ability of rat BMSCs expressing human VEGFA165 (hVEGF165) to promote tissue repair in rat model of radiation-induced injury.Methods Rat BMSCs were isolated from the tibia.Plasmid DNA expressing hVEGF165 was stably transfected into BMSCs using liposomes.The right hindlimb muscle of 40 rats was irradiated using a 60Co y source (total dose 30 Gy).The animals were divided into four groups (n=10):not injected with BMSCs (control; group 1) or intramuscularly injected two times (once in 2 weeks) with pcDNATM3.1-transfected BMSCs (group 2),untransfected BMSCs (group 3),or hVEGF165-transfected BMSCs (group 4).Angiography was performed 1 week after the last injection of BMSCs; samples of the hindlimb muscle were subjected to transmission electron microscopy,ultrastructural analysis,reverse transcription-PCR (RT-PCR),Western blotting,and immunohistochemistry.Results Rat BMSCs with multipotent differentiation capacity were isolated,hVEGF165-transfected BMSCs overexpressed hVEGF165 mRNA and protein.Injection of BMSCs (groups 2-4) increased the average vessel number,density,diameter,and cross-sectional area; mRNA expression of the myogenic markers including myoblast determination protein,myogenin,and α-smooth muscle actin; and CD31 protein expression; and promoted the repair of blood vessels and myofibers after radiation-induced injury compared to group 1; each of these parameters and hVEGF165 mRNA or protein expression were markedly improved in rats injected with hVEGF165-transfected BMSCs compared to groups 2 and 3.Conclusions BMSCs expressing hVEGF165 enhanced the repair of radiation-induced tissue injury by promoting vasculogenesis and muscle fiber regeneration.BMSCs expressing h

  18. Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Kuang, G M; Yau, W P; Lu, W W; Chiu, K Y

    2013-07-01

    We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft-bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL-bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.

  19. Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

    Science.gov (United States)

    Freeman, Fiona E; McNamara, Laoise M

    2017-04-01

    Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for

  20. Polymeric composites containing carbon nanotubes for bone tissue engineering.

    Science.gov (United States)

    Sahithi, Kolli; Swetha, Maddela; Ramasamy, Kumarasamy; Srinivasan, Narasimhan; Selvamurugan, Nagarajan

    2010-04-01

    Several natural and synthetic polymers are now available for bone tissue engineering applications but they may lack mechanical integrity. In recent years, there are reports emphasizing the importance of carbon nanotubes (CNTs) in supporting bone growth. CNTs possess exceptional mechanical, thermal, and electrical properties, facilitating their use as reinforcements or additives in various materials to improve the properties of the materials. Biomaterials containing polymers often are placed adjacent to bone. The use of CNTs is anticipated in these biomaterials applied to bone mainly to improve their overall mechanical properties and expected to act as scaffolds to promote and guide bone tissue regeneration. This review paper provides a current state of knowledge available examining the use of the polymeric composites containing CNTs for promoting bone growth.

  1. The use of a new miniature cryoprobe for ablation of bone tissue: In vivo assessment of the probe and application of the method to bone in a sheep model

    Directory of Open Access Journals (Sweden)

    König Dietmar-Pierree

    2003-04-01

    Full Text Available Abstract Background So far, modern miniature cryoprobes were used for local destruction of soft tissue tumours without damaging the adjacent healthy tissue. In this study, cryoablation methodology was applied to bone and the cooling capacity of the probe was examined in vitro and in vivo. Method Freezing was performed by cooling one or two probes (diameter 3.2 mm to -180°C with liquid nitrogen. The cooling capacity of the probes was determined optically and thermally against a homogeneous reference gel, followed by in vivo measurements on femoral and tibial sheep bone followed by histological examination. Results Thanks to the synergistic effect, the simultaneous use of 2 probes produced an almost spherical expansion of cold in the homogenous gelatin. During the in vivo freezes, the temperature curves showed a more moderate trend. Nevertheless, due to the synergistic effect, temperatures below -50°C could be reached at a distance of 1 cm from the probe. No local or systemic intraoperative complications were observed. Histological examination revealed cell necrosis up into the -10°C isotherm. Conclusions Adequate tissue cooling of the bone matrix can be achieved with in vivo freezes by means of one or more miniature cryoprobes. Therefore, this probe could provide an alternative to or supplement surgical resection of pathological bone processes.

  2. Tissue reaction and material characteristics of four bone substitutes

    DEFF Research Database (Denmark)

    Jensen, S S; Aaboe, M; Pinholt, E M

    1996-01-01

    The aim of the present study was to qualitatively and quantitatively compare the tissue reactions around four different bone substitutes used in orthopedic and craniofacial surgery. Cylinders of two bovine bone substitutes (Endobon and Bio-Oss) and two coral-derived bone substitutes (Pro Osteon 500......-Oss was osseointegrated to a higher degree than the other biomaterials. Material characteristics obtained by diffuse reflectance infrared Fourier transform spectrometry analysis and energy-dispersive spectrometry did not explain the differences in biologic behavior....

  3. Stem and progenitor cells: advancing bone tissue engineering.

    Science.gov (United States)

    Tevlin, R; Walmsley, G G; Marecic, O; Hu, Michael S; Wan, D C; Longaker, M T

    2016-04-01

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone--the best option--is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

  4. Micromechanical finite element modeling and experimental characterization of the compressive mechanical properties of polycaprolactone:hydroxyapatite composite scaffolds prepared by selective laser sintering for bone tissue engineering

    Science.gov (United States)

    Eshraghi, Shaun; Das, Suman

    2012-01-01

    Bioresorbable scaffolds with mechanical properties suitable for bone tissue engineering were fabricated from polycaprolactone (PCL) and hydroxyapatite (HA) by selective laser sintering (SLS) and modeled by finite element analysis (FEA). Both solid gage parts and scaffolds having 1-D, 2-D and 3-D orthogonal, periodic porous architectures were made with 0, 10, 20 and 30% HA by volume. PCL:HA scaffolds manufactured by SLS had nearly full density (99%) in the designed solid regions and had excellent geometric and dimensional control. Through optimization of the SLS process, the compressive moduli for our solid gage parts and scaffolds are the highest reported in the literature for additive manufacturing. The compressive moduli of solid gage parts were 299.3, 311.2, 415.5 and 498.3 MPa for PCL:HA loading at 100:0, 90:10, 80:20 and 70:30 respectively. The compressive effective stiffness tended to increase as the loading of HA was increased and the designed porosity was lowered. In the case of the most 3-D porous scaffold, the compressive modulus more than doubled from 14.9 MPa to 36.2 MPa when changing the material from 100:0 to 70:30 PCL:HA. A micromechanical finite element analysis (FEA) model was developed to investigate the reinforcement effect of HA loading on the compressive modulus of the bulk material. Using a first-principles based approach, the random distribution of HA particles in a solidified PCL matrix was modeled for any loading of HA to predict the bulk mechanical properties of the composites. The bulk mechanical properties were also used for FEA of the scaffold geometries. Results of the FEA were found to be in good agreement with experimental mechanical testing. The development of patient and site-specific composite tissue engineering constructs with tailored properties can be seen as a direct extension of this work on computational design, a priori modeling of mechanical properties and direct digital manufacturing. PMID:22522129

  5. In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation.

    Science.gov (United States)

    Wittkowske, Claudia; Reilly, Gwendolen C; Lacroix, Damien; Perrault, Cecile M

    2016-01-01

    This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodeling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g., due to extended periods of bed rest or microgravity in space are associated with altered bone remodeling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signaling factors, such as nitric oxide, and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signaling, collagen deposition, and matrix mineralization. Particular attention is given to in vitro set-ups, which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibers, which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  6. In vitro bone cell models: Impact of fluid shear stress on bone formation

    Directory of Open Access Journals (Sweden)

    Claudia Wittkowske

    2016-11-01

    Full Text Available This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodelling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g. due to extended periods of bed rest or microgravity in space are associated with altered bone remodelling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signalling factors such as nitric oxide and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signalling, collagen deposition and matrix mineralization. Particular attention is given to in vitro set-ups which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibres which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  7. Biomechanical researches on tissue engineering bone constructed by deproteinated bone

    Institute of Scientific and Technical Information of China (English)

    JIAN Yue-kui; TIAN Xiao-bin; LI Qi-hong; LI Bo; PENG Zhi; ZHAO Wei-feng; WANG Yuan-zheng; YANG Zhen

    2010-01-01

    Objective:To study biomechanical changes of newly formed bones 24 weeks after repairing large defects of long bones of goats using heterogeneous deproteinated bone(DPB)prepared by modified methods as an engineering scaffold.Methods:According to a fully randomized design,18 goats were evenly divided into three groups:normal bone control group(Group A),autologous bone group(Group B)and experimental group(Group C).Each goat in Groups B and C were subjected to the periosteum and bone defect at middle-lower part of the fight tibia(20% of the whole tibia in length),followed by autologous bone or DPB plus autologous MSCs + rhBMP2 implantation,respectively and semiring slot fixation;while goats in Group A did not perform osteotomy.At 24 weeks after surgery,biomechanical tests were carried out on the tibias.Results:At 24 weeks after surgery,the results of anticompression test on tibias in three groups were recorded by a functional recorder presented as linear pressure-deformation curve.The shapes of the curves and their change tendency were similar among three groups.The ultimate pressure values were 10.74 Mpa±1.23 Mpa,10.11 Mpa±1.35 Mpa and 10.22 Mpa±1.32 Mpa and fracture compression rates were 26.82%±0.87%,27.17%±0.75% and 28.22%±1.12% in Groups A,B and C,respectively.Comparisons of anti-compression ultimate pressures and fracture compression rates among three groups demonstrated no significant difference(P_(AB)=0.415,P_(BC)=0.494).Three-point antibend test on tibias was recorded as load-deformation curves,and the shapes of the curves and their change tendency were similar among three groups.The ultimate pressure values of the anti-bend test were 481.52 N±12.45 N,478.34 N±14.68 N and 475.62 N±13.41 N and the fracture bend rates were 2.62 mm±0.12 mm,2.61 mm±0.15 mm and 2.81 mm±0.13 mm in Groups A,B and C,respectively.There was no significant difference between groups(P_(AB)=0.7,P_(BC)=0.448).The ultirates were 29.51°±1.64°,28.88°±1.46° and 28.81°±1.33

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

    Science.gov (United States)

    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.

  9. Biodegradable Polymer-Based Scaffolds for Bone Tissue Engineering

    CERN Document Server

    Sultana, Naznin

    2013-01-01

    This book addresses the principles, methods and applications of biodegradable polymer based scaffolds for bone tissue engineering. The general principle of bone tissue engineering is reviewed and the traditional and novel scaffolding materials, their properties and scaffold fabrication techniques are explored. By acting as temporary synthetic extracellular matrices for cell accommodation, proliferation, and differentiation, scaffolds play a pivotal role in tissue engineering. This book does not only provide the comprehensive summary of the current trends in scaffolding design but also presents the new trends and directions for scaffold development for the ever expanding tissue engineering applications.

  10. VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease.

    Directory of Open Access Journals (Sweden)

    Mallikarjun Badadani

    Full Text Available Dominant mutations in the valosin containing protein (VCP gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD. We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumulation of TDP-43 and ubiquitin-positive inclusion bodies in quadriceps myofibrils and brain. Increased LC3-II staining of muscle sections representing increased number of autophagosomes suggested impaired autophagy. Increased apoptosis was demonstrated by elevated caspase-3 activity and increased TUNEL-positive nuclei. X-ray microtomography (uCT images show radiolucency of distal femurs and proximal tibiae in knock-in mice and uCT morphometrics shows decreased trabecular pattern and increased cortical wall thickness. Bone histology and bone marrow derived macrophage cultures in these mice revealed increased osteoclastogenesis observed by TRAP staining suggestive of Paget bone disease. The VCP(R155H/+ knock-in mice replicate the muscle, bone and brain pathology of inclusion body myopathy, thus representing a useful model for preclinical studies.

  11. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    Science.gov (United States)

    Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Valenzano, Anna; Esposito, Teresa; Cibelli, Giuseppe

    2017-01-01

    Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

  12. Melatonin Effects on Hard Tissues: Bone and Tooth

    Directory of Open Access Journals (Sweden)

    Hong-Wen He

    2013-05-01

    Full Text Available Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been investigated relative to bone remolding, osteoporosis, osseointegration of dental implants and dentine formation. In the present review, we discuss the large body of published evidence and review data of melatonin effects on hard tissues, specifically, bone and tooth.

  13. Is bone tissue really affected by swimming? A systematic review.

    Directory of Open Access Journals (Sweden)

    Alejandro Gómez-Bruton

    Full Text Available BACKGROUND: Swimming, a sport practiced in hypogravity, has sometimes been associated with decreased bone mass. AIM: This systematic review aims to summarize and update present knowledge about the effects of swimming on bone mass, structure and metabolism in order to ascertain the effects of this sport on bone tissue. METHODS: A literature search was conducted up to April 2013. A total of 64 studies focusing on swimmers bone mass, structure and metabolism met the inclusion criteria and were included in the review. RESULTS: It has been generally observed that swimmers present lower bone mineral density than athletes who practise high impact sports and similar values when compared to sedentary controls. However, swimmers have a higher bone turnover than controls resulting in a different structure which in turn results in higher resistance to fracture indexes. Nevertheless, swimming may become highly beneficial regarding bone mass in later stages of life. CONCLUSION: Swimming does not seem to negatively affect bone mass, although it may not be one of the best sports to be practised in order to increase this parameter, due to the hypogravity and lack of impact characteristic of this sport. Most of the studies included in this review showed similar bone mineral density values in swimmers and sedentary controls. However, swimmers present a higher bone turnover than sedentary controls that may result in a stronger structure and consequently in a stronger bone.

  14. Hydroxyapatite-titanium bulk composites for bone tissue engineering applications.

    Science.gov (United States)

    Kumar, Alok; Biswas, Krishanu; Basu, Bikramjit

    2015-02-01

    The research work on bulk hydroxyapatite (HA)-based composites are driven by the need to develop biomaterials with better mechanical properties without compromising its bioactivity and biocompatibility properties. Despite several years of research, the mechanical properties of the HA-based composites still need to be enhanced to match the properties of natural cortical bone. In this regard, the scope of this review on the HA-based bulk biomaterials is limited to the processing and the mechanical as well as biocompatibility properties for bone tissue engineering applications of a model system that is hydroxyapatite-titanium (HA-Ti) bulk composites. It will be discussed in this review how HA-Ti based bulk composites can be processed to have better fracture toughness and strength without compromising biocompatibility. The advantages of the functionally gradient materials to integrate the mechanical and biocompatibility properties is a promising approach in hard tissue engineering and has been emphasized here in reference to the limited literature reports. On the biomaterials fabrication aspect, the recent results are discussed to demonstrate that advanced manufacturing techniques, like spark plasma sintering can be adopted as a processing route to restrict the sintering reactions, while enhancing the mechanical properties. Various toughening mechanisms related to careful tailoring of microstructure are discussed. The in vitro cytocompatibilty, cell fate processes as well as in vivo biocompatibility results are also reviewed and the use of flow cytometry to quantify in vitro cell fate processes is being emphasized. © 2014 Wiley Periodicals, Inc.

  15. Effects of microgravity on rat bone, cartlage and connective tissues

    Science.gov (United States)

    Doty, S.

    1990-01-01

    The response to hypogravity by the skeletal system was originally thought to be the result of a reduction in weight bearing. Thus a reduced rate of new bone formation in the weight-bearing bones was accepted, when found, as an obvious result of hypogravity. However, data on non-weight-bearing tissues have begun to show that other physiological changes can be expected to occur to animals during spaceflight. This overview of the Cosmos 1887 data discusses these results as they pertain to individual bones or tissues because the response seems to depend on the architecture and metabolism of each tissue under study. Various effects were seen in different tissues from the rats flown on Cosmos 1887. The femur showed a reduced bone mineral content but only in the central region of the diaphysis. This same region in the tibia showed changes in the vascularity of bone as well as some osteocytic cell death. The humerus demonstrated reduced morphometric characteristics plus a decrease in mechanical stiffness. Bone mineral crystals did not mature normally as a result of flight, suggesting a defect in the matrix mineralization process. Note that these changes relate directly to the matrix portion of the bone or some function of bone which slowly responds to changes in the environment. However, most cellular functions of bone are rapid responders. The stimulation of osteoblast precursor cells, the osteoblast function in collagen synthesis, a change in the proliferation rate of cells in the epiphyseal growth plate, the synthesis and secretion of osteocalcin, and the movement of water into or out of tissues, are all processes which respond to environmental change. These rapidly responding events produced results from Cosmos 1887 which were frequently quite different from previous space flight data.

  16. Composites structures for bone tissue reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Neto, W.; Santos, João [Universidade Federal de São Carlos, Departament of Materials Engineering - Rd. Washington Luis, Km 235, 13565-905, São Carlos-SP (Brazil); Avérous, L.; Schlatter, G.; Bretas, Rosario, E-mail: bretas@ufscar.br [Université de Strasbourg, ECPM-LIPHT - 25 rue Becquerel, 67087, Strasbourg (France)

    2015-05-22

    The search for new biomaterials in the bone reconstitution field is growing continuously as humane life expectation and bone fractures increase. For this purpose, composite materials with biodegradable polymers and hydroxyapatite (HA) have been used. A composite material formed by a film, nanofibers and HA has been made. Both, the films and the non-woven mats of nanofibers were formed by nanocomposites made of butylene adipate-co-terephthalate (PBAT) and HA. The techniques used to produce the films and nanofibers were spin coating and electrospinning, respectively. The composite production and morphology were evaluated. The composite showed an adequate morphology and fibers size to be used as scaffold for cell growth.

  17. An adaptation model for trabecular bone at different mechanical levels

    Directory of Open Access Journals (Sweden)

    Lv Linwei

    2010-07-01

    Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

  18. Training human mesenchymal stromal cells for bone tissue engineering applications

    NARCIS (Netherlands)

    Doorn, J.

    2012-01-01

    Human mesenchymal stromal cells (hMSCs) are an interesting source for cell therapies and tissue engineering applications, because these cells are able to differentiate into various target tissues, such as bone, cartilage, fat and endothelial cells. In addition, they secrete a wide array of growth fa

  19. Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model

    Directory of Open Access Journals (Sweden)

    Barrientos-Durán A

    2014-09-01

    Full Text Available Antonio Barrientos-Durán,1,5,* Ellen M Carpenter,2 Nicole I zur Nieden,3 Theodore I Malinin,4 Juan Carlos Rodríguez-Manzaneque,5 Laura P Zanello1,* 1Department of Biochemistry, University of California Riverside, Riverside, CA, USA; 2Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, South Los Angeles, CA, USA; 3Department of Cell Biology and Neuroscience, Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside, Riverside, CA, USA; 4Tissue Bank, Department of Orthopedics, University of Miami Miller School of Medicine, Miami, FL, USA; 5Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO, Granada, Spain *These authors contributed equally to this workAbstract: The clinical management of bone defects caused by trauma or nonunion fractures remains a challenge in orthopedic practice due to the poor integration and biocompatibility properties of the scaffold or implant material. In the current work, the osteogenic properties of carboxyl-modified single-walled carbon nanotubes (COOH–SWCNTs were investigated in vivo and in vitro. When human preosteoblasts and murine embryonic stem cells were cultured on coverslips sprayed with COOH–SWCNTs, accelerated osteogenic differentiation was manifested by increased expression of classical bone marker genes and an increase in the secretion of osteocalcin, in addition to prior mineralization of the extracellular matrix. These results predicated COOH–SWCNTs’ use to further promote osteogenic differentiation in vivo. In contrast, both cell lines had difficulties adhering to multi-walled carbon nanotube-based scaffolds, as shown by scanning electron microscopy. While a suspension of SWCNTs caused cytotoxicity in both cell lines at levels >20 µg/mL, these levels were never achieved by release from sprayed SWCNTs, warranting the approach taken. In vivo, human allografts formed by the

  20. Wide-field Raman imaging for bone detection in tissue

    OpenAIRE

    Papour, Asael; Kwak, Jin Hee; Taylor, Zach; Wu, Benjamin; Stafsudd, Oscar; Grundfest, Warren

    2015-01-01

    Inappropriate bone growth in soft tissue can occur after trauma to a limb and can cause a disruption to the healing process. This is known as Heterotopic Ossification (HO) in which regions in the tissue start to mineralize and form microscopic bone-like structures. These structures continue to calcify and develop into large, non-functional bony masses that cause pain, limit limb movement, and expose the tissue to reoccurring infections; in the case of open wounds this can lead to amputation a...

  1. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage

    DEFF Research Database (Denmark)

    Day, J; Ding, Ming; van der Linden, JC

    2001-01-01

    In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage....... Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were...... determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected...

  2. Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Tegan L Cheng

    2015-10-01

    Full Text Available Sucrose acetate isobutyrate (SAIB is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2 and found synergy when co-delivering zoledronic acid (ZA and hydroxyapatite (HA nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP nor Bioglass (BG 45S5 had a significant effect on bone volume (BV alone or in combination with the ZA. 14C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%, and BV was further increased with ZA–adsorbed micro-HA and nano-HA (+530% and +889%. These data support the use of ZA–adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering.

  3. A tissue regeneration approach to bone and cartilage repair

    CERN Document Server

    Dunstan, Colin; Rosen, Vicki

    2015-01-01

    Reviewing exhaustively the current state of the art of tissue engineering strategies for regenerating bones and joints through the use of biomaterials, growth factors and stem cells, along with an investigation of the interactions between biomaterials, bone cells, growth factors and added stem cells and how together skeletal tissues can be optimised, this book serves to highlight the importance of biomaterials composition, surface topography, architectural and mechanical properties in providing support for tissue regeneration. Maximizing reader insights into the importance of the interplay of these attributes with bone cells (osteoblasts, osteocytes and osteoclasts) and cartilage cells (chondrocytes), this book also provides a detailed reference as to how key signalling pathways are activated. The contribution of growth factors to drive tissue regeneration and stem cell recruitment is discussed along with a review the potential and challenges of adult or embryonic mesenchymal stem cells to further enhance the...

  4. Bone Tissue in Down Syndrome Patients Deteriorates Following Aging: A Study Based on Bone Ultrasound Analysis

    Directory of Open Access Journals (Sweden)

    Mirela Gavris

    2014-03-01

    Conclusion: This study showed that BUA is sufficiently sensitive to highlight the bone degradation that occurs at the end of adolescence and in adulthood in individuals with DS. In addition, BUA and stabilometric performances were able to distinguish DS patients from controls in the two older age groups, indicating that bone tissue and postural control of DS patients deteriorate with aging.

  5. Whole Body Bone Tissue and Cardiovascular Risk in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Claudiu Popescu

    2014-01-01

    Full Text Available Introduction. Atherosclerosis and osteoporosis share an age-independent bidirectional correlation. Rheumatoid arthritis (RA represents a risk factor for both conditions. Objectives. The study aims to evaluate the connection between the estimated cardiovascular risk (CVR and the loss of bone tissue in RA patients. Methods. The study has a prospective cross-sectional design and it includes female in-patients with RA or without autoimmune diseases; bone tissue was measured using whole body dual X-ray absorptiometry (wbDXA; CVR was estimated using SCORE charts and PROCAM applications. Results. There were 75 RA women and 66 normal women of similar age. The wbDXA bone indices correlate significantly, negatively, and age-independently with the estimated CVR. The whole body bone percent (wbBP was a significant predictor of estimated CVR, explaining 26% of SCORE variation along with low density lipoprotein (P < 0.001 and 49.7% of PROCAM variation along with glycemia and menopause duration (P < 0.001. Although obese patients had less bone relative to body composition (wbBP, in terms of quantity their bone content was significantly higher than that of nonobese patients. Conclusions. Female patients with RA and female patients with cardiovascular morbidity have a lower whole body bone percent. Obese female individuals have higher whole body bone mass than nonobese patients.

  6. Effect of the “protein diet” and bone tissue.

    Science.gov (United States)

    Nascimento da Silva, Zoraide; Azevedo de Jesuz, Vanessa; De Salvo Castro, Eduardo; Soares da Costa, Carlos Alberto; Teles Boaventura, Gilson; Blondet de Azeredo, Vilma

    2014-01-01

    The aim of this study is to evaluate the effect of the hyperproteic diet consumption on bone tissue. The study was conducted during sixty days. Twenty eight Wistar albinus rats, adults, originated from Laboratory of Experimental Nutrition were divided in four groups: (n = 7); Control 1 (C1), Control 2 (C2), Hyperproteic 1 (HP1) e Hyperproteic 2 (HP2). The C2 and HP2 groups were submitted to 30% of food restriction. The hyperproteic diet was based on the Atkins diet and prepared to simulate the protein diet. At the end of the study the animals were anesthetized to performer bone densitometry analyses by DEXA and blood and tissue collection. Serum and bone minerals analyses were conducted by colorimetric methods in automated equipment. The total bone mineral density (BMD) of the pelvis and the spine of the food restriction groups (HP2 e C2) were lower (p hyperproteic groups (HP1 e HP2). It was observed similar effect on the osteocalcin level, that presented lower (p hyperproteic groups. The insulin level was lower only in HP2 and serum calcium of the HP1 and HP2 groups was lower than C1. The protein diet promotes significant bone change on femur and in the hormones levels related to bone synthesis and maintenance of this tissue.

  7. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Directory of Open Access Journals (Sweden)

    Ye Li

    2015-07-01

    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  8. A piezoelectric actuator-driven loading device for mechanical condition during bone tissue engineering

    Science.gov (United States)

    Zhang, C. Q.; Wu, H.; Dong, X.

    2008-10-01

    Bone cells live in an environment heavily influenced by mechanical forces. The researches of bone cell responses in hard scaffolds under differently mechanical conditions will be greatly beneficial to elucidating the mechanisms of bone mechanotransduction as well as applications of mechanical condition in bone tissue engineering. However, the appropriate device for the experiments is prerequisite. A loading device suitable to hard scaffold for study on mechanical responses of bone cells was made by usage of a kind of long-travel, high-load piezoelectric actuator. The device, which is so small enough to work in a standard incubator, can cause hard scaffolds with directly uniaxial compressive strains with more magnitudes, frequency components, and waveforms, including bone physiologically mechanical state, precisely controlled by a computer. The device achieves precise mechanical conditions by testing verification. The device may produce a model that will be suitable for investigating the influences of mechanical responses on bone cells in 3D hard scaffolds in vitro matching that in cancellous bone in vivo and may be applied during bone tissue engineering culture.

  9. Tannerella forsythia infection-induced calvarial bone and soft tissue transcriptional profiles.

    Science.gov (United States)

    Bakthavatchalu, V; Meka, A; Sathishkumar, S; Lopez, M C; Bhattacharyya, I; Boyce, B F; Mans, J J; Lamont, R J; Baker, H V; Ebersole, J L; Kesavalu, L

    2010-10-01

    Tannerella forsythia is associated with subgingival biofilms in adult periodontitis, although the molecular mechanisms contributing to chronic inflammation and loss of periodontal bone remain unclear. We examined changes in the host transcriptional profiles during a T. forsythia infection using a murine calvarial model of inflammation and bone resorption. Tannerella forsythia was injected into the subcutaneous soft tissue over calvariae of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated and Murine GeneChip (Affymetrix, Santa Clara, CA) array analysis of transcript profiles showed that 3226 genes were differentially expressed in the infected soft tissues (P < 0.05) and 2586 genes were differentially transcribed in calvarial bones after infection. Quantitative real-time reverse transcription-polymerase chain reaction analysis of transcription levels of selected genes corresponded well with the microarray results. Biological pathways significantly impacted by T. forsythia infection in calvarial bone and soft tissue included leukocyte transendothelial migration, cell adhesion molecules (immune system), extracellular matrix-receptor interaction, adherens junction, and antigen processing and presentation. Histologic examination revealed intense inflammation and increased osteoclasts in calvariae compared with controls. In conclusion, localized T. forsythia infection differentially induces transcription of a broad array of host genes, and the profiles differ between inflamed soft tissues and calvarial bone.

  10. Multiscale patterned transplantable stem cell patches for bone tissue regeneration.

    Science.gov (United States)

    Kim, Jangho; Bae, Won-Gyu; Choung, Han-Wool; Lim, Ki Taek; Seonwoo, Hoon; Jeong, Hoon Eui; Suh, Khap-Yang; Jeon, Noo Li; Choung, Pill-Hoon; Chung, Jong Hoon

    2014-11-01

    Stem cell-based therapy has been proposed as an enabling alternative not only for the treatment of diseases but also for the regeneration of tissues beyond complex surgical treatments or tissue transplantation. In this study, we approached a conceptual platform that can integrate stem cells into a multiscale patterned substrate for bone regeneration. Inspired by human bone tissue, we developed hierarchically micro- and nanopatterned transplantable patches as synthetic extracellular matrices by employing capillary force lithography in combination with a surface micro-wrinkling method using a poly(lactic-co-glycolic acid) (PLGA) polymer. The multiscale patterned PLGA patches were highly flexible and showed higher tissue adhesion to the underlying tissue than did the single nanopatterned patches. In response to the anisotropically multiscale patterned topography, the adhesion and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled. Furthermore, the stem cell patch composed of hMSCs and transplantable PLGA substrate promoted bone regeneration in vivo when both the micro- and nanotopography of the substrate surfaces were synergistically combined. Thus, our study concludes that multiscale patterned transplantable stem cell patches may have a great potential for bone regeneration as well as for various regenerative medicine approaches.

  11. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    Science.gov (United States)

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

  12. Microarchitectural adaptations in aging and osteoarthrotic subchondral bone tissues

    DEFF Research Database (Denmark)

    Ding, Ming

    2010-01-01

    The human skeleton optimizes its microarchitecture by elaborate adaptations to mechanical loading during development and growth. The mechanisms for adaptation involve a multistep process of cellular mechanotransduction stimulating bone modelling, and remodeling resulting in either bone formation...... into the age-related and OA-related subchondral bone adaptations.   Microarchitectural adaptation in human aging cancellous bone The precision of micro-CT measurement is excellent. Accurate 3-D micro-CT image datasets can be generated by applying an appropriate segmentation threshold. A fixed threshold may...... and the constant nature of connectivity suggest an important bone remodeling mechanism that normal aging tibia may adapt trabecular volume orientation. Namely, that the aging trabeculae align preferentially to the primary loading direction to compensate bone loss (III). Age-related changes in trabecular thickness...

  13. Local mechanical stimuli regulate bone formation and resorption in mice at the tissue level.

    Directory of Open Access Journals (Sweden)

    Friederike A Schulte

    Full Text Available Bone is able to react to changing mechanical demands by adapting its internal microstructure through bone forming and resorbing cells. This process is called bone modeling and remodeling. It is evident that changes in mechanical demands at the organ level must be interpreted at the tissue level where bone (remodeling takes place. Although assumed for a long time, the relationship between the locations of bone formation and resorption and the local mechanical environment is still under debate. The lack of suitable imaging modalities for measuring bone formation and resorption in vivo has made it difficult to assess the mechanoregulation of bone three-dimensionally by experiment. Using in vivo micro-computed tomography and high resolution finite element analysis in living mice, we show that bone formation most likely occurs at sites of high local mechanical strain (p<0.0001 and resorption at sites of low local mechanical strain (p<0.0001. Furthermore, the probability of bone resorption decreases exponentially with increasing mechanical stimulus (R(2 = 0.99 whereas the probability of bone formation follows an exponential growth function to a maximum value (R(2 = 0.99. Moreover, resorption is more strictly controlled than formation in loaded animals, and ovariectomy increases the amount of non-targeted resorption. Our experimental assessment of mechanoregulation at the tissue level does not show any evidence of a lazy zone and suggests that around 80% of all (remodeling can be linked to the mechanical micro-environment. These findings disclose how mechanical stimuli at the tissue level contribute to the regulation of bone adaptation at the organ level.

  14. Bone Tissue Engineering Challenges in Oral & Maxillofacial Surgery.

    Science.gov (United States)

    Smith, Brandon T; Shum, Jonathan; Wong, Mark; Mikos, Antonios G; Young, Simon

    2015-01-01

    Over the past decades, there has been a substantial amount of innovation and research into tissue engineering and regenerative approaches for the craniofacial region. This highly complex area presents many unique challenges for tissue engineers. Recent research indicates that various forms of implantable biodegradable scaffolds may play a beneficial role in the clinical treatment of craniofacial pathological conditions. Additionally, the direct delivery of bioactive molecules may further increase de novo bone formation. While these strategies offer an exciting glimpse into potential future treatments, there are several challenges that still must be overcome. In this chapter, we will highlight both current surgical approaches for craniofacial reconstruction and recent advances within the field of bone tissue engineering. The clinical challenges and limitations of these strategies will help contextualize and inform future craniofacial tissue engineering strategies.

  15. Gene therapy for cartilage and bone tissue engineering

    CERN Document Server

    Hu, Yu-Chen

    2014-01-01

    "Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

  16. Porcine Bone Scaffolds Adsorb Growth Factors Secreted by MSCs and Improve Bone Tissue Repair

    Directory of Open Access Journals (Sweden)

    Eitan Mijiritsky

    2017-09-01

    Full Text Available An ideal tissue-engineered bone graft should have both excellent pro-osteogenesis and pro-angiogenesis properties to rapidly realize the bone regeneration in vivo. To meet this goal, in this work a porcine bone scaffold was successfully used as a Trojan horse to store growth factors produced by mesenchymal stem cells (MSCs. This new scaffold showed a time-dependent release of bioactive growth factors, such as vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF, in vitro. The biological effect of the growth factors-adsorbed scaffold on the in vitro commitment of MSCs into osteogenic and endothelial cell phenotypes has been evaluated. In addition, we have investigated the activity of growth factor-impregnated granules in the repair of critical-size defects in rat calvaria by means of histological, immunohistochemical, and molecular biology analyses. Based on the results of our work bone tissue formation and markers for bone and vascularization were significantly increased by the growth factor-enriched bone granules after implantation. This suggests that the controlled release of active growth factors from porcine bone granules can enhance and promote bone regeneration.

  17. Mechanochemical synthesis evaluation of nanocrystalline bone-derived bioceramic powder using for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Amirsalar Khandan

    2014-01-01

    Full Text Available Introduction: Bone tissue engineering proposes a suitable way to regenerate lost bones. Different materials have been considered for use in bone tissue engineering. Hydroxyapatite (HA is a significant success of bioceramics as a bone tissue repairing biomaterial. Among different bioceramic materials, recent interest has been risen on fluorinated hydroxyapatites, (FHA, Ca 10 (PO 4 6 F x (OH 2−x . Fluorine ions can promote apatite formation and improve the stability of HA in the biological environments. Therefore, they have been developed for bone tissue engineering. The aim of this study was to synthesize and characterize the FHA nanopowder via mechanochemical (MC methods. Materials and Methods: Natural hydroxyapatite (NHA 95.7 wt.% and calcium fluoride (CaF 2 powder 4.3 wt.% were used for synthesis of FHA. MC reaction was performed in the planetary milling balls using a porcelain cup and alumina balls. Ratio of balls to reactant materials was 15:1 at 400 rpm rotation speed. The structures of the powdered particles formed at different milling times were evaluated by X-ray diffraction (XRD, scanning electron microscopy (SEM and transmission electron microscopy (TEM. Results: Fabrication of FHA from natural sources like bovine bone achieved after 8 h ball milling with pure nanopowder. Conclusion: F− ion enhances the crystallization and mechanical properties of HA in formation of bone. The produced FHA was in nano-scale, and its crystal size was about 80-90 nm with sphere distribution in shape and size. FHA powder is a suitable biomaterial for bone tissue engineering.

  18. Evaluation of bone tissue reaction in laser beamed implants

    Energy Technology Data Exchange (ETDEWEB)

    Allegrini, Sergio, E-mail: sergiojr@usp.br [Graduate Program in Biodentistry, Ibirapuera University (UNIB), São Paulo, SP, 04661 100 (Brazil); Yoshimoto, Marcelo [Graduate Program in Biodentistry, Ibirapuera University (UNIB), São Paulo, SP, 04661 100 (Brazil); Salles, Marcos Barbosa [Department of Oral and Maxillofacial Surgery, Nove de Julho University (UNINOVE), São Paulo, SP, 02117 010 (Brazil); Allegrini, Marcia Rivellino Facci [São Paulo Fire Department (SPFD) of the Militar Police, Dentistry Section, São Paulo, SP, 01018 001 (Brazil); Pistarini, Luciana Crepaldi Yazawa; Braga, Francisco Jose Correa; Bressiani, Ana Helena de Almeida [Nuclear and Energy Research Institute – IPEN/USP, São Paulo, SP, 05508 900 (Brazil)

    2014-07-01

    The purpose of this study was to evaluate alterations and bone tissue response on laser treated implant surfaces (Nd:YAG – 100 W). Sixty grade II titanium (ASTM F67) mini-implants (1.5 mm × 4.0 mm) were installed in femurs of 30 Wistar rats. The animals were divided into two groups: thirty mini-implants were machined elements (Machined Group) and the other thirty had laser beamed surfaces (Laser Group). The animals were subdivided into three groups, according to bone healing periods of 15, 30 and 60 days. The samples were analyzed under light, scanning electron and confocal 3D microscopy as well as by EDS (energy dispersive spectroscopy) and Student's t test was used for statistical analyses. Light microscopy results showed new bone trabeculae formation toward laser-treated implants at 15 days’ bone repair as well as thin layers of osteoid matrix, indicating high biocompatibility. Similar features were observed in the Machined Group but only after 30 days. Bone/implant contact was better evidenced on laser-treated surfaces compared to that on simply machined implants. The only group that demonstrated change in level of significance was the laser-treated group at the 15-day-healing period (p < 0.05). Higher oxygen concentration possibly provides more efficient response of osteoblasts during new bone tissue deposition. Implant treated surfaces altered by laser beaming, their composition, surface topography and surface energy may be the future scene in implant dentistry.

  19. Template-Mediated Biomineralization for Bone Tissue Engineering.

    Science.gov (United States)

    Leiendecker, Alexander; Witzleben, Steffen; Schulze, Margit; Tobiasch, Edda

    2017-01-01

    Template-mediated mineralization describes a research field of materials chemistry that deals with templates influencing product formation of foremost inorganic functional materials and composites. These templates are usually organic compounds - as far as molecules with natural origin are involved, the terminology "biomineralization" or "biomimetic mineralization: is used. The present review gives insight into recent developments in the research area of bone-tissue engineering with focus on chemical templates and cell-based approaches. The review is structured as follows: (1) a brief general overview about the principle of templating and recently used template materials, (2) important analytical methods, (3) examples of template-guided mineralization of various bone-related materials, (4) natural bone mineralization, (5) scaffolds for bone-tissue regeneration and (6) cell-based therapeutic approaches. For this purpose, a literature screening with emphasis on promising potential practical applications was performed. In particular, macromolecular structures and polymer composites with relation to naturally occurring compounds were favored. Priority was given to publications of the last five years. Although the present review does not cover the whole topic to full extent, it should provide information about current trends and the most promising approaches in the research area of bone-tissue engineering based on applications of organic templates/scaffolds as well as cell-based strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Wang Mayao

    2015-01-01

    Full Text Available 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

  2. Effect of the "protein diet" and bone tissue

    Directory of Open Access Journals (Sweden)

    Zoraide Nascimento da Silva

    2014-01-01

    Full Text Available The aim of this study is to evaluate the effect of the hyperproteic diet consumption on bone tissue. Methods: The study was conducted during sixty days. Twenty eight Wistar albinus rats, adults, originated from Laboratory of Experimental Nutrition were divided in four groups: (n = 7; Control 1 (C1, Control 2 (C2, Hyperproteic 1 (HP1 e Hyperproteic 2 (HP2. The C2 and HP2 groups were submitted to 30% of food restriction. The hyperproteic diet was based on the Atkins diet and prepared to simulate the protein diet. At the end of the study the animals were anesthetized to performer bone densitometry analyses by DEXA and blood and tissue collection. Serum and bone minerals analyses were conducted by colorimetric methods in automated equipment. Results: The total bone mineral density (BMD of the pelvis and the spine of the food restriction groups (HP2 e C2 were lower (p < 0.05 than C1 e HP1 groups. While the femur BMD of the HP2 was lower (p < 0.05 related to others groups. It had been observed reduction (p < 0.05 in the medium point of the width of femur diaphysis and in bone calcium level in the hyperproteic groups (HP1 e HP2. It was observed similar effect on the osteocalcin level, that presented lower (p < 0.05 in the hyperproteic groups. The insulin level was lower only in HP2 and serum calcium of the HP1 and HP2 groups was lower than C1. Conclusion: The protein diet promotes significant bone change on femur and in the hormones levels related to bone synthesis and maintenance of this tissue.

  3. Clinical Application of Human Mesenchymal Stromal Cells for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Anindita Chatterjea

    2010-01-01

    Full Text Available The gold standard in the repair of bony defects is autologous bone grafting, even though it has drawbacks in terms of availability and morbidity at the harvesting site. Bone-tissue engineering, in which osteogenic cells and scaffolds are combined, is considered as a potential bone graft substitute strategy. Proof-of-principle for bone tissue engineering using mesenchymal stromal cells (MSCs has been demonstrated in various animal models. In addition, 7 human clinical studies have so far been conducted. Because the experimental design and evaluation parameters of the studies are rather heterogeneous, it is difficult to draw conclusive evidence on the performance of one approach over the other. However, it seems that bone apposition by the grafted MSCs in these studies is observed but not sufficient to bridge large bone defects. In this paper, we discuss the published human clinical studies performed so far for bone-tissue regeneration, using culture-expanded, nongenetically modified MSCs from various sources and extract from it points of consideration for future clinical studies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Doğan, Ayşegül; Demirci, Selami [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey); Bayir, Yasin [Department of Biochemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Halici, Zekai [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karakus, Emre [Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum (Turkey); Aydin, Ali [Department of Orthopedics and Traumatology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Cadirci, Elif [Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Albayrak, Abdulmecit [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Demirci, Elif [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karaman, Adem [Department of Radiology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Ayan, Arif Kursat [Department of Nuclear Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Gundogdu, Cemal [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Şahin, Fikrettin, E-mail: fsahin@yeditepe.edu.tr [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey)

    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. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing.

  5. Mathematical model for bone mineralization

    Directory of Open Access Journals (Sweden)

    Svetlana V Komarova

    2015-08-01

    Full Text Available Defective bone mineralization has serious clinical manifestations, including deformities and fractures, but the regulation of this extracellular process is not fully understood. We have developed a mathematical model consisting of ordinary differential equations that describe collagen maturation, production and degradation of inhibitors, and mineral nucleation and growth. We examined the roles of individual processes in generating normal and abnormal mineralization patterns characterized using two outcome measures: mineralization lag time and degree of mineralization. Model parameters describing the formation of hydroxyapatite mineral on the nucleating centers most potently affected the degree of mineralization, while the parameters describing inhibitor homeostasis most effectively changed the mineralization lag time. Of interest, a parameter describing the rate of matrix maturation emerged as being capable of counter-intuitively increasing both the mineralization lag time and the degree of mineralization. We validated the accuracy of model predictions using known diseases of bone mineralization such as osteogenesis imperfecta and X-linked hypophosphatemia. The model successfully describes the highly non-linear mineralization dynamics, which includes an initial lag phase when osteoid is present but no mineralization is evident, then fast primary mineralization, followed by secondary mineralization characterized by a continuous slow increase in bone mineral content. The developed model can potentially predict the function for a mutated protein based on the histology of pathologic bone samples from mineralization disorders of unknown etiology.

  6. Efficient biomarkers for the characterization of bone tissue.

    Science.gov (United States)

    Gil, J E; Aranda, J P; Mérida-Casermeiro, E; Ujaldón, M

    2012-12-01

    This work describes an expert system aimed to an accurate classification of cell tissue on microscopic images coming from studies of bone tissue regeneration from stem cells. We analyze a wide number of phenotype and color issues to build effective vectors of features for the subsequent characterization of tissue into five different classes: bone, cartilage, muscle, fiber and spine. The features selection includes texture, shape and color descriptors, among which we consider color histograms, Zernike moments and circular parameters. Once a preliminary set of vectors candidates are selected, several trained and non-parametric classifiers based on neural networks, decision trees, Bayesian classifiers and association rules are analyzed, and later compared with unsupervised methods to determine those that fit more closely to our needs for distinguishing bone tissue. Because of the high resolution of our biomedical images, we effectively decompose them into smaller windows for a faster execution, with the impact of the window size being discussed in terms of speed and robustness. Our final study compares accuracy and computational time together with different stainings for revealing tissue properties: Picrosirius red, alcian blue and safranin blue. Overall, safranin blue reveals as the best staining and multilayer perceptron as the most effective classifier.

  7. Wide-field Raman imaging for bone detection in tissue.

    Science.gov (United States)

    Papour, Asael; Kwak, Jin Hee; Taylor, Zach; Wu, Benjamin; Stafsudd, Oscar; Grundfest, Warren

    2015-10-01

    Inappropriate bone growth in soft tissue can occur after trauma to a limb and can cause a disruption to the healing process. This is known as Heterotopic Ossification (HO) in which regions in the tissue start to mineralize and form microscopic bone-like structures. These structures continue to calcify and develop into large, non-functional bony masses that cause pain, limit limb movement, and expose the tissue to reoccurring infections; in the case of open wounds this can lead to amputation as a result of a failed wound. Both Magnetic Resonance Imaging (MRI) and X-ray imaging have poor sensitivity and specificity for the detection of HO, thus delaying therapy and leading to poor patient outcomes. We present a low-power, fast (1 frame per second) optical Raman imaging system with a large field of view (1 cm(2)) that can differentiate bone tissue from soft tissue without spectroscopy, this in contrast to conventional Raman microscopy systems. This capability may allow for the development of instrumentation which permits bedside diagnosis of HO.

  8. Immature muscular tissue differentiation into bone-like tissue by bone morphogenetic proteins in vitro, with ossification potential in vivo.

    Science.gov (United States)

    Hayashi, Tatsuhide; Kobayashi, Syuichiro; Asakura, Masaki; Kawase, Mayu; Ueno, Atsuko; Uematsu, Yasuaki; Kawai, Tatsushi

    2014-09-01

    The objective of this study was to induce bone formation from immature muscular tissue (IMT) in vitro, using bone morphogenetic proteins (BMPs) as a cytokine source and an expanded polytetrafluoroethylene (ePTFE) scaffold. In addition, cultured IMTs were implanted subcutaneously into Sprague-Dawley (SD) rats to determine their in vivo ossification potential. BMPs, extracted from bovine cortical bones, were applied to embryonic SD rat IMT cultures, before 2 weeks culture on ePTFE scaffolds. Osteoblast-like cells and osteoid tissues were partially identified by hematoxylin-eosin staining 2 weeks after culture. Collagen type I (Col-I), osteopontin (OP), and osteocalcin (OC) were detected in the osteoid tissues by immunohistochemical staining. OC gene expression remained low, but OP and Col-I were upregulated during the culture period. In vivo implanted IMTs showed slight radiopacity 1 week after implantation and strong radiopacity 2 and 3 weeks after implantation. One week after implantation, migration of numerous capillaries was observed and ossification was detected after 2 weeks by histological observation. These results suggest that IMTs are able to differentiate into bone-like tissue in vitro, with an ossification potential after implantation in vivo.

  9. Tissue engineering bone using autologous progenitor cells in the peritoneum.

    Directory of Open Access Journals (Sweden)

    Jinhui Shen

    Full Text Available Despite intensive research efforts, there remains a need for novel methods to improve the ossification of scaffolds for bone tissue engineering. Based on a common phenomenon and known pathological conditions of peritoneal membrane ossification following peritoneal dialysis, we have explored the possibility of regenerating ossified tissue in the peritoneum. Interestingly, in addition to inflammatory cells, we discovered a large number of multipotent mesenchymal stem cells (MSCs in the peritoneal lavage fluid from mice with peritoneal catheter implants. The osteogenic potential of these peritoneal progenitor cells was demonstrated by their ability to easily infiltrate decalcified bone implants, produce osteocalcin and form mineralized bone in 8 weeks. Additionally, when poly(l-lactic acid scaffolds loaded with bone morphogenetic protein-2 (a known osteogenic differentiation agent were implanted into the peritoneum, signs of osteogenesis were seen within 8 weeks of implantation. The results of this investigation support the concept that scaffolds containing BMP-2 can stimulate the formation of bone in the peritoneum via directed autologous stem and progenitor cell responses.

  10. Evaluation of the bone healing process in an experimental tibial bone defect model in ovariectomized rats.

    Science.gov (United States)

    Kido, Hueliton Wilian; Bossini, Paulo Sérgio; Tim, Carla Roberta; Parizotto, Nivaldo Antônio; da Cunha, Anderson Ferreira; Malavazi, Iran; Renno, Ana Claudia Muniz

    2014-10-01

    The aim of this study was to evaluate the influence of postmenopausal bone loss (induced by ovariectomy) in the process of bone healing in a tibial bone defect model in rats by means of histological evaluation of bone defects and the analysis of the expression of genes and proteins involved in bone consolidation. Twenty female Wistar rats (12 weeks old, weighing ±250 g) were randomly divided into two groups: control group (CG) and ovariectomized group (OG). Rats of OG were submitted to ovariectomy and after 8 weeks post-surgery, all animals were submitted to the tibial bone defect model. The main histological finding analysis revealed that ovariectomized animals showed a higher amount of granulation tissue and immature newly formed bone compared to CG. Furthermore, quantitative histological analysis showed that OG presented a significant decrease in the amount of newly formed bone (p = 0.0351). RT-PCR analysis showed no difference in Runx2, ALP, RANK, RANKL and Osterix gene expression 14-day post-surgery. Interestingly, immunohistochemical evaluation showed that Runx2 was down expressed (p = 0.0001) and RANKL was up expressed (p = 0.0022) in the OG. In conclusion, these data highlight that bone loss induced by ovariectomy causes an impairment in the capacity of bone to heal mainly probably because of alterations in the imbalance of osteoblasts and osteoclasts activities.

  11. [Distribution of compact bone mesenchymal stem cells in lung tissue and bone marrow of mouse].

    Science.gov (United States)

    Wang, Rui-Ping; Wu, Ren-Na; Guo, Yu-Qing; Zhang, Bin; Chen, Hu

    2014-02-01

    This study was aimed to investigate the distribution of compact bone mesenchymal stem cells(MSC) marked with lentiviral plasmid pGC FU-RFP-LV in lung tissue and bone marrow of mouse. The MSC were infected by lentivirus with infection efficiency 78%, the infected MSC were injected into BALB/c mice via tail veins in concentration of 1×10(6) /mouse. The mice were randomly divided into 4 group according to 4 time points as 1, 2, 5 and 7 days. The lung tissue and bone marrow were taken and made of frozen sections and smears respectively in order to observed the distributions of MSC. The results indicated that the lentiviral infected MSC displayed phenotypes and biological characteristics which conformed to MSC by immunophenotyping analysis and induction differentiation detection. After the MSC were infected with optimal viral titer MOI = 50, the cell growth no significantly changed; the fluorescent microscopy revealed that the distributions of MSC in bone marrow on day 1, 2, 5 and 7 were 0.50 ± 0.20, 0.67 ± 0.23, 0.53 ± 0.14, 0.33 ± 0.16; those in lung tissue were 0.55 ± 0.15, 0.47 ± 0.13, 0.29 ± 0.13, 0.26 ± 0.08. It is concluded that the distribution of MSC in lung tissue reaches a peak on day 1, while distribution of MSC in bone marrow reaches a peak on day 2. The distribution of mouse MSC relates with RFP gene expression and implantation of MSC in lung tissue and bone marrow.

  12. Effect of Ankaferd Blood Stopper on Early Bone Tissue Healing in ...

    African Journals Online (AJOL)

    on bone healing; in fact, ABS increases inflammation in vivo. Keywords: Ankaferd blood stopper, Wound healing, Mineralized bone tissue, Inflammatory cell infiltration, Osteoid tissue, Tooth ... rodent diet ad libitum. All procedures were.

  13. In vivo cyclic loading as a potent stimulatory signal for bone formation inside tissue engineering scaffold

    Directory of Open Access Journals (Sweden)

    A Roshan-Ghias

    2010-02-01

    Full Text Available In clinical situations, bone defects are often located at load bearing sites. Tissue engineering scaffolds are future bone substitutes and hence they will be subjected to mechanical stimulation. The goal of this study was to test if cyclic loading can be used as stimulatory signal for bone formation in a bone scaffold. Poly(L-lactic acid (PLA/ 5% beta-tricalcium phosphate (beta-TCP scaffolds were implanted in both distal femoral epiphyses of eight rats. Right knees were stimulated (10N, 4Hz, 5 min five times, every two days, starting from the third day after surgery while left knees served as control. Finite element study of the in vivo model showed that the strain applied to the scaffold is similar to physiological strains. Using micro-computed tomography (CT, all knees were scanned five times after the surgery and the related bone parameters of the newly formed bone were quantified. Statistical modeling was used to estimate the evolution of these parameters as a function of time and loading. The results showed that mechanical stimulation had two effects on bone volume (BV: an initial decrease in BV at week 2, and a long-term increase in the rate of bone formation by 28%. At week 13, the BV was then significantly higher in the loaded scaffolds.

  14. Multiscale Modeling of Bone

    Science.gov (United States)

    2014-12-01

    stiffnesses are in GPa. Location Femm Tibia Femur Femur Method illtrasound Mechanical illtrasound illtrasound Preferential Model Testing 95%EFM...0.2654 Femoral Neck [103] 0.2067 0.172 Femoral Head [104] 0.27 0.2 Distal Femm [105] 0.27 0.19 Proximal Femur [105] 0.105 Greater Trochanter [103...stiffer in compression than tension for all models. Additionally, the distal and proximal femm is stiffer than both the femoral neck and head. This is

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

    Science.gov (United States)

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

    2014-09-01

    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.

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

    Science.gov (United States)

    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.

  17. Ionic Colloidal Molding as a Biomimetic Scaffolding Strategy for Uniform Bone Tissue Regeneration.

    Science.gov (United States)

    Zhang, Jian; Jia, Jinpeng; Kim, Jimin P; Shen, Hong; Yang, Fei; Zhang, Qiang; Xu, Meng; Bi, Wenzhi; Wang, Xing; Yang, Jian; Wu, Decheng

    2017-02-21

    Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro. Based on this biomimetic approach, it is herein demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. Lastly, better controlled biomaterial degradation significantly improved osteointegration, translating to highly regular bone formation with minimal fibrous tissue and increased bone density in rabbit radial defect models. Ionic colloidal molding is a simple yet effective approach of achieving materials homogeneity and modulating crystal nucleation, serving as an excellent biomimetic scaffolding strategy to rebuild natural bone integrity.

  18. A MULTI-SITE SHEEP MODEL FOR CANCELLOUS BONE HEALING

    Directory of Open Access Journals (Sweden)

    Angad eMalhotra

    2014-09-01

    Full Text Available Appropriate, well characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14mm of fixed depth (25mm were compared in both skeletally immature (18 month old and aged sheep (5 year old. In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bilaterally. Animals were euthanized at four weeks post-operatively to assess early healing and any biological response. Defect sites were graded radiographically, and new bone formation quantified using µCT and histomorphometry. Fibrous tissue was found within the central region in most of the defects, with woven bone normally forming near the periphery of the defect. Bone volume fraction (BV/TV significantly decreased with an increasing defect diameter. Actual bone volume (BV, however, increased with defect diameter. Bone ingrowth was lower for all defect diameters in the aged group. This pilot study proposes that the surgical creation of 11mm diameter defects in the proximal tibial and distal femoral epiphyses of aged sheep is a suitable large animal model to study early healing of cancellous bone defects. The refined model allows for the placement of four separate bone defects per animal, and encourages a reduction in animal numbers required for preclinical research.

  19. Preparation of laponite bioceramics for potential bone tissue engineering applications.

    Directory of Open Access Journals (Sweden)

    Chuanshun Wang

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

  20. Preparation of laponite bioceramics for potential bone tissue engineering applications.

    Science.gov (United States)

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

    2014-01-01

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

  1. Massive osteoradionecrosis of facial bones and soft tissues.

    Science.gov (United States)

    Benlier, E; Alicioglu, B; Kocak, Z; Yurdakul-Sikar, E; Top, H

    2009-01-01

    Osteoradionecrosis (ORN) is one of the most serious and uncommon complications in head and neck irradiation for cancer. It is defined as a combination of necrotic soft tissue and bone not being able to heal spontaneously, it demonstrates a general resistance to antibiotics and requires conservative surgical management. Even with modern radiation therapy, its incidence is highly unpredictable and varies between 4-30%. We report on a patient with a huge open cavitation in the cheek, communicating with the mouth and extending to contralateral periodontal gingival and temporal fossa. He had been treated with radiation therapy for nasopharyngeal cancer 5 years ago and presented with restriction of the opening of the mouth. Osteonecrosis complicated with osteomyelitis was evident in bilateral mandible and maxillary bones and the temporal bone. The ramus of the mandible and zygomatic arc were resected, subtotal maxillectomy was performed and the defect was repaired by a free double island flap from the scapular and parascapular osteocutaneous latissimus dorsi muscle flap supplied by subscapular artery. To our knowledge, this is the most extensive bone and soft tissue destruction due to radiation reported in the literature.

  2. Biodegradable Materials for Bone Repair and Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh

    2015-08-01

    Full Text Available This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results.

  3. Novel Scaffolds Fabricated Using Oleuropein for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hui Fan

    2014-01-01

    Full Text Available We investigated the feasibility of oleuropein as a cross-linking agent for fabricating three-dimensional (3D porous composite scaffolds for bone tissue engineering. Human-like collagen (HLC and nanohydroxyapatite (n-HAp were used to fabricate the composite scaffold by way of cross-linking. The mechanical tests revealed superior properties for the cross-linked scaffolds compared to the uncross-linked scaffolds. The as-obtained composite scaffold had a 3D porous structure with pores ranging from 120 to 300 μm and a porosity of 73.6±2.3%. The cross-linked scaffolds were seeded with MC3T3-E1 Subclone 14 mouse osteoblasts. Fluorescence staining, the Cell Counting Kit-8 (CCK-8 assay, and scanning electron microscopy (SEM indicated that the scaffolds enhanced cell adhesion and proliferation. Our results indicate the potential of these scaffolds for bone tissue engineering.

  4. METABOLIC CHANGES OF CONNECTIVE TISSUE IN CHILDREN WITH BONE CYST

    Directory of Open Access Journals (Sweden)

    O. M. Magomedov

    2013-10-01

    Full Text Available The results of the study of diagnostically important metabolism parameters in patients with bone cysts in different stages of the disease are presented. It is shown that an increase activity of protein banding collagenase, alkaline phosphatase and also of hydroxyproline, glycosaminoglycans contents due to lower levels of calcium and inorganic phosphate levels increase in blood serum are expressed in a stage osteolysis than the step of separating. Decreasing the amount of glycosaminoglycans and collagen in bone indicates an intensification of catabolic processes in the connective tissue matrix. Diagnostically important indicators of the degree of disturbance of bone metabolism are the level of collagen, proteoglycans and activity of marker enzymes — collagenase and alkaline phosphatase. Based on the evaluation of sensitivity, specificity and diagnostic efficiency of the obtained results, we can recommend the threshold values of the investigated parameters of basic organic components and mineral metabolism of bone for the differential diagnosis of stages of bone cysts in children, which will serve as a basis for the development of appropriate diagnostic tests.

  5. The Pathology of Bone Tissue during Peri-Implantitis

    OpenAIRE

    Schminke, B.; vom Orde, F.; Gruber, R.; H Schliephake; Bürgers, R; Miosge, N

    2015-01-01

    Dental implants are one of the most frequently used treatment options for tooth replacement. Approximately 30% of patients with dental implants develop peri-implantitis, which is an oral inflammatory disease that leads to loss of the supporting tissues, predominately the bone. For the development of future therapeutic strategies, it is essential to understand the molecular pathophysiology of human dental peri-implant infections. Here, we describe the gene and protein expression patterns of pe...

  6. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    Science.gov (United States)

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    There is an ongoing need to understand the mechanisms of bone marrow-based allograft tolerance. This is important in clarifying the diverse variables influencing the ultimate outcome of the solid organ and composite tissue transplants. To establish bone marrow transplantation as a routine clinical application, further experimental studies should be conducted to overcome the obstacles related to the bone marrow transplantation. These obstacles include graft versus host disease, immunocompetence, and toxicity of the conditioning regimens. For these purposes, novel experimental models are needed. In an attempt to provide a reliable research tool for bone marrow-based tolerance induction studies, we introduced different experimental models of modified vascularized skin/bone marrow (VSBM) transplantation technique for tolerance induction, monitoring, and maintenance studies. In this skin/bone transplantation model, the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants was investigated. Isograft transplantations were performed between genetically identical Lewis (LEW, RT1) rats. Five different experimental designs in 5 groups of 5 animals each were studied. Group I: Bilateral vascularized skin (VS) transplantation; group II: bilateral vascularized skin/bone transplantation; group III: vascularized skin transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group IV: vascularized bone transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group V: vascularized bone transplantation on one side and vascularized skin transplantation on the contralateral side. Successful transplantations were performed in all groups. The survival of the isograft transplants was evaluated clinically and histologically. All skin flaps remained pink and pliable and grew new

  7. Exercise and Regulation of Bone and Collagen Tissue Biology

    DEFF Research Database (Denmark)

    Kjær, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja Maria

    2015-01-01

    , and tolerable load within weeks, to a degree (30-40%) that mimics that of contractile skeletal musculature. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity......The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle......, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular...

  8. Thallium-201 scintigraphy for bone and soft tissue tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tokuumi, Yuji; Tsuchiya, Hiroyuki; Sunayama, Chiaki; Matsuda, Eizo; Asada, Naohiro; Taki, Junichi; Sumiya, Hisashi; Miyauchi, Tsutomu; Tomita, Katsuro [Kanazawa Univ. (Japan). School of Medicine

    1995-05-01

    This study was undertaken to assess the usefulness of thallium-201 scintigraphy in bone and soft tissue tumors. Pre-therapy scintigraphy was undertaken in a total of 136 patients with histologically confirmed diagnosis, consisting of 74 with malignant bone and soft tissue tumors, 39 with benign ones, 12 with diseases analogous to tumors, and 11 others. Thallium activity was graded on a scale of 0-4: 0=background activity, 1=equivocal activity, 2=definitive activity, but less than myocardium, 3=definite activity equal to myocardium, and 4=activity greater than myocardium. In the group of malignant tumors, thallium-201 uptake was found in 80%, although it was low for chondrosarcoma (2/8) and malignant Schwannoma (one/3). The group of benign tumors, however, showed it in only 41%, being restricted to those with giant cell tumors, chondroblastoma, fibromatosis, and osteoid osteoma. Thallium-201 uptake was also found in all 8 patients with metastatic tumors. In 23 patients undergoing thallium imaging before and after chemotherapy, scintigraphic findings revealed a high correlation with histopathological findings. Thus, thallium-201 scintigraphy may be potentially used to distinguish malignant from benign bone and soft tissue tumors, except for a few histopathological cases, as well as to determine loco-regional metastases and response to chemotherapy. (N.K.).

  9. [Project to enhance bone bank tissue storage and distribution procedures].

    Science.gov (United States)

    Huang, Jui-Chen; Wu, Chiung-Lan; Chen, Chun-Chuan; Chen, Shu-Hua

    2011-10-01

    Organ and tissue transplantation are now commonly preformed procedures. Improper organ bank handling procedures may increase infection risks. Execution accuracy in terms of tissue storage and distribution at our bone bank was 80%. We thus proposed an execution improvement project to enhance procedures in order to fulfill the intent of donors and ensure recipient safety. This project was designed to raise nurse professionalism, and ensure patient safety through enhanced tissue storage and distribution procedures. Education programs developed for this project focus on teaching standard operating procedures for bone and ligament storage and distribution, bone bank facility maintenance, trouble shooting and solutions, and periodic inspection systems. Cognition of proper storage and distribution procedures rose from 81% to 100%; Execution accuracy also rose from 80% to 100%. The project successfully conveyed concepts essential to the correct execution of organ storage and distribution procedures and proper organ bank facility management. Achieving and maintaining procedural and management standards is crucial to continued organ donations and the recipient safety.

  10. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    Science.gov (United States)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  11. 3D bone tissue growth in hollow fibre membrane bioreactor: implications of various process parameters on tissue nutrition.

    Science.gov (United States)

    Abdullah, N S; Das, D B; Ye, H; Cui, Z F

    2006-09-01

    New experimental evidence shows that hollow fibre membrane bioreactor (HFMB) may be applied to grow bulky bone tissues which may then be implanted into patients to repair skeletal defects. To design effective bone tissue engineering protocols, it is necessary to determine the quantitative relationships between the cell environment and tissue behaviour in HFMBs and their relationship with nutrient supply. It is also necessary to determine under what conditions nutritional limitations may occur and, hence, may cause cell death. These require that the appropriate bioreactor conditions for generating neotissues, and the nutrient transfer behaviour and chemical reaction during cell growth and extracellular matrix formation are studied thoroughly. In this paper, we aim to use an existing mathematical framework to analyse the influence of various relevant parameters on nutrient supply for bone tissue growth in HFMB. We adopt the well-known Krogh cylinder approximation of the HFMB. The model parameters (e.g., cell metabolic rates) and operating conditions for the mathematical model have been obtained from, or correspond to, in-house experiments with the exception of a few variables which have been taken from the literature. The framework is then used to study oxygen and glucose transport behaviour in the HFMB. Influence of a number of important process parameters, e.g., reaction kinetics, cell density, inlet concentration of nutrients, etc, on the nutrient distributions have been systematically analysed. The work presented in this paper provides insights on unfavourable system designs and specifications which may be avoided to prevent mass transfer limitations for growing bone tissues in HFMB.

  12. Quality Indices Of Jaw Bone Tissue In Screening Diagnostics Of Parodontal Diseases

    Directory of Open Access Journals (Sweden)

    V.P. Konev

    2009-12-01

    Full Text Available The objective of the work is to develop and motivate screening methods of the estimation of paradontal tissues by digital X-ray study. The used methods are X-ray digital scene with estimation of bone tissue density in program Trophy 2000, clinically anatomical parallels of bone tissue density and their qualitative indices. Parallels between qualitative indices of bones of mandibular alveolar process and bone tissue density of these areas have been revealed. It is reasonable to carry out the estimation of bone tissue density indices for revealing early stages of parodontal pathology

  13. Assessment of bone tissue during treatment dentoalveolar anomalies in children with scoliosis

    Directory of Open Access Journals (Sweden)

    Samoilenko A.V.

    2012-01-01

    Full Text Available The purpose of the study was to develop a rational method of treatment dentoalveolar anomalies aimed at reducing relapses dentoalveolar anomalies, duration of treatment, depending on bone density in patients with scoliosis. Scoliosis is often associated with osteopenia and impaired metabolism of connective tissue that manifested reduced bone mineral density and changes in metabolic status, impaired synthesis of the major structural components of connective tissue, resulting integral reaction to a combination of two abnormal situations - osteopenia and scoliotic deformity. Prevalence dentoalveolar anomalies abnormalities among patients with scoliosis reaches 81.6%, in most cases accompanied by gingivitis. Therefore, the need for orthodontic treatment in these patients is quite high. When scoliosis orthodontic treatment has an impact on pathologically changed bone, so the retention period of orthodontic treatment need prescriptions that enhance the adaptive capacity of the body and promote reparative bone formation and development of pathogenetically substantiated complex preventive measures aimed at improving the effectiveness of treatment and prevention of dentoalveolar anomalies recurrence. A biometric study of control and diagnostic models of the jaws, biochemical oral fluid, determining bone density by ultrasonic osteography, the timing of orthodontic treatment in patients, with jaw abnormalities suffering from scoliosis and various sites of varying severity. We have developed medical centers showed high efficiency, which showed an increase density and improve bone metabolism.

  14. First cosmic-ray images of bone and soft tissue

    Science.gov (United States)

    Mrdja, Dusan; Bikit, Istvan; Bikit, Kristina; Slivka, Jaroslav; Hansman, Jan; Oláh, László; Varga, Dezső

    2016-11-01

    More than 120 years after Roentgen's first X-ray image, the first cosmic-ray muon images of bone and soft tissue are created. The pictures, shown in the present paper, represent the first radiographies of structures of organic origin ever recorded by cosmic rays. This result is achieved by a uniquely designed, simple and versatile cosmic-ray muon-imaging system, which consists of four plastic scintillation detectors and a muon tracker. This system does not use scattering or absorption of muons in order to deduct image information, but takes advantage of the production rate of secondaries in the target materials, detected in coincidence with muons. The 2D image slices of cow femur bone are obtained at several depths along the bone axis, together with the corresponding 3D image. Real organic soft tissue, polymethyl methacrylate and water, never seen before by any other muon imaging techniques, are also registered in the images. Thus, similar imaging systems, placed around structures of organic or inorganic origin, can be used for tomographic imaging using only the omnipresent cosmic radiation.

  15. Osteogenesis for postoperative temporal bone defects using human ear adipose-derived stromal cells and tissue engineering: an animal model study.

    Science.gov (United States)

    Kim, Yeon Ju; Park, Seung Gu; Shin, Beomyong; Kim, Jangho; Kim, Seung Won; Choo, Oak-Sung; Yin, Xiang Yun; Min, Byoung Hyun; Choung, Yun-Hoon

    2017-09-05

    Mastoidectomy, the removal of infected mastoid bones, is a common surgical procedure for the treatment of chronic otitis media. Persistent and recurrent otorrhea and accumulation of keratin debris following open cavity mastoidectomy are still bothersome issues for both patients and otologists. In this study, we used human ear adipose-derived stromal cells (hEASCs) in combination with polycaprolactone (PCL) scaffolds and osteogenic differentiation medium (ODM) to regenerate temporal bone defects. The hEASCs showed stem cell phenotypes, and these characteristics were maintained up to passage 5. Mastoid bulla and cranial bone defects were induced in Sprague-Dawley rats using AgNO3 and burr hole drilling, respectively, and the rats were then divided into five groups: (1) control, (2) hEASCs, (3) hEASCs + ODM, (4) hEASCs + PCL scaffolds, and (5) hEASCs + PCL scaffolds + ODM. Osteogenesis was evaluated by micro-computed tomography and histology. Compared with the control group, the groups transplanted with hEASCs and PCL scaffolds had significantly higher bone formation along the periphery of the mastoid bulla area. Moreover, ODM synergistically enhanced bone formation in mastoid bulla defects. Our results suggest that combining hEASCs with PCL scaffolds represents a promising method for anatomical and functional reconstruction of postoperative temporal bone defects following mastoidectomy. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.

  16. Adipose mesenchymal stem cells in the field of bone tissue engineering.

    Science.gov (United States)

    Romagnoli, Cecilia; Brandi, Maria Luisa

    2014-04-26

    Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians. Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility, biodegradability and osteoinductivity. Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells (MSCs). In particular, a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue. These adipose stem cells (ASCs) can be obtained in large quantities with little donor site morbidity or patient discomfort, in contrast to the invasive and painful isolation of bone marrow MSCs. The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models, with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients. Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration, the lack of standardization in applied techniques makes the comparison between studies difficult. Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns, which must be resolved to permit application in regenerative medicine.

  17. Nerve Tissue Prefabrication Inside the Rat Femoral Bone: Does It Work?

    Science.gov (United States)

    Ozbek, Zuhtu; Kocman, Atacan Emre; Ozatik, Orhan; Soztutar, Erdem; Ozkara, Emre; Kose, Aydan; Arslantas, Ali; Cetin, Cengiz

    2017-01-01

    To investigate whether nerve regeneration can be induced in the tubular bone between distal and proximal cut nerve ends. Twenty adult Wistar rats were used for the study. Rats were divided into three groups; femoral bone conduit group, nerve transection group, sham group. The sciatic nerve was surgically cut and from both ends inserted into the adjacent femoral bone tunnel in the femoral bone conduit group. The sciatic nerve was cut transversely in the nerve transection group. In the Sham group, only sciatic nerve exploration was performed, without a nerve cut. The groups were evaluated functionally and morphologically. All results showed that axonal growth existed through the osseous canal. To the best of our knowledge, this is the first study to evaluate neural regeneration inside the bone. We can speculate that the bone marrow provides a convenient microenvironment for peripheral nerve regeneration. In addition to prefabricating peripheral nerves, this novel model may help to establish further strategies for engineering of other tissues in the bone marrow.

  18. 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.

    Science.gov (United States)

    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.

  19. The evolution of simulation techniques for dynamic bone tissue engineering in bioreactors.

    Science.gov (United States)

    Vetsch, Jolanda Rita; Müller, Ralph; Hofmann, Sandra

    2015-08-01

    Bone tissue engineering aims to overcome the drawbacks of current bone regeneration techniques in orthopaedics. Bioreactors are widely used in the field of bone tissue engineering, as they help support efficient nutrition of cultured cells with the possible combination of applying mechanical stimuli. Beneficial influencing parameters of in vitro cultures are difficult to find and are mostly determined by trial and error, which is associated with significant time and money spent. Mathematical simulations can support the finding of optimal parameters. Simulations have evolved over the last 20 years from simple analytical models to complex and detailed computational models. They allow researchers to simulate the mechanical as well as the biological environment experienced by cells seeded on scaffolds in a bioreactor. Based on the simulation results, it is possible to give recommendations about specific parameters for bone bioreactor cultures, such as scaffold geometries, scaffold mechanical properties, the level of applied mechanical loading or nutrient concentrations. This article reviews the evolution in simulating various aspects of dynamic bone culture in bioreactors and reveals future research directions.

  20. 3D conductive nanocomposite scaffold for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Shahini A

    2013-12-01

    Full Text Available Aref Shahini,1 Mostafa Yazdimamaghani,2 Kenneth J Walker,2 Margaret A Eastman,3 Hamed Hatami-Marbini,4 Brenda J Smith,5 John L Ricci,6 Sundar V Madihally,2 Daryoosh Vashaee,1 Lobat Tayebi2,7 1School of Electrical and Computer Engineering, Helmerich Advanced Technology Research Center, 2School of Chemical Engineering, 3Department of Chemistry, 4School of Mechanical and Aerospace Engineering, 5Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA; 6Department of Biomaterials and Biomimetics, New York University, New York, NY; 7School of Material Science and Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK, USA Abstract: Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene poly(4-styrene sulfonate (PEDOT:PSS, in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent

  1. Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

    Directory of Open Access Journals (Sweden)

    Dirk Henrich

    2015-01-01

    Full Text Available Bone marrow mononuclear cells (BMCs are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma, demineralized bone matrix (DBM, and bovine cancellous bone (BS were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo.

  2. Comparative study of cryopreserved bone tissue and tissue preserved in a 98% glycerol solution

    OpenAIRE

    GIOVANI, Arlete Mazzini Miranda; Croci, Alberto Tesconi; Oliveira,Cláudia Regina GCM; Filippi,Renée Zon; Santos, Luiz Augusto U.; Maragni,Graziela G; Albhy,Thays Moreira

    2006-01-01

    OBJECTIVE: To compare the bone graft cryopreservation method (at -80ºC) with a preservation method using a 98% glycerol solution at room temperature (10ºC-35ºC), by testing the antibacterial and fungal effects of 98% glycerol and comparatively analyzing the observed histological changes resulting from the use of both methods. METHOD: This study was of 30 samples of trabecular bone tissue from 10 patients undergoing total hip arthroplasty. Each femoral head provided 3 samples that were randomi...

  3. Links between cyclosporin exposure in tissues and graft-versus-host disease in pediatric bone marrow transplantation: analysis by a PBPK model.

    Science.gov (United States)

    Gérard, Cécile; Bleyzac, Nathalie; Girard, Pascal; Freyer, Gilles; Bertrand, Yves; Tod, Michel

    2011-03-01

    In hematopoietic stem cell transplantation (HSCT), cyclosporin is used to prevent graft-versus-host disease (GVHD). However, cyclosporin distribution in tissues is not linear, resulting in uncertainty regarding optimal dosing and monitoring. The objective of this study was to link the probability and severity of acute GVHD to cyclosporin exposure in blood, GVHD target organs, and lymphoid organs. A physiologically based pharmacokinetic model of cyclosporin disposition and logistic regression models were used. Sixty-one pediatric patients undergoing HSCT were studied. Cyclosporin was administered by intermittent (n = 31) or continuous infusion (n = 30). At steady state (1 day before acute GVHD), exposures in all organs were related with the probability and severity of acute GVHD. Average cyclosporin concentration or, equivalently, its area under the curve (AUC) was the pharmacokinetic index best correlated with the anti-GVHD effect. Cyclosporin AUC in interstitial fluid of lymphoid organs was a superior index than that in blood, but marginally. Hence, AUC in blood maybe used as an index of cyclosporin efficacy. Using our model, target AUCs in blood could be defined for malignant and non-malignant diseases, as well as the equivalent target values for C(2) and C(0) concentrations.

  4. Effect of the "protein diet" and bone tissue

    OpenAIRE

    Zoraide Nascimento da Silva; Vanessa Azevedo de Jesuz; Eduardo de Salvo Castro; Carlos Alberto Soares da Costa; Gilson Teles Boaventura; Vilma Blondet de Azeredo

    2014-01-01

    The aim of this study is to evaluate the effect of the hyperproteic diet consumption on bone tissue. Methods: The study was conducted during sixty days. Twenty eight Wistar albinus rats, adults, originated from Laboratory of Experimental Nutrition were divided in four groups: (n = 7); Control 1 (C1), Control 2 (C2), Hyperproteic 1 (HP1) e Hyperproteic 2 (HP2). The C2 and HP2 groups were submitted to 30% of food restriction. The hyperproteic diet was based on the Atkins diet and prepared to si...

  5. Effect of the gamma radiation and common antioxidants on some aspects of osteoblast differentiation during the formation of bone tissue in an in-vivo model; Efecto de la radiacion gamma y antioxidantes comunes sobre algunos aspectos de la diferenciacion de los osteoblastos durante la formacion de tejido oseo en un modelo in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Quinones O, M. G.

    2015-07-01

    Gamma radiation is the emission of energy through short electromagnetic waves to a higher level of frequency with respect to ultraviolet light. This type of energy in the medical application is used as a tool to kill cancer cells in humans, however, adverse damages to its exposure can produce secondary effects in the short and long term depending on the damage in cells and tissues nearby to the irradiation zone, the human body will present various injuries and conditions. In bone tissue, secondary effects that have been observed, is an alteration of the architecture and integrity of bone extracellular matrix of cortical and trabecular tissue, which causes loss of bone density. However, the reason that the bone tissue is affected is not clear, but is believed to be related to the formation of free radicals, which generate oxidative damage in biomolecules of the cells, damaging the tissue structure, organs and systems of the human body. The studies to identify the main reasons that will affect bone tissue as a result of radiotherapy have been carried out by models In-vitro and some In-vivo. In most studies in-vitro with cells with osteoblast phenotype, the results suggest alterations in proliferation and differentiation of these cells. However, the etiology and the role of these changes in disorders and bone injuries as adverse secondary effects of the radiotherapy are very poorly understood to date. In the present study an In-vivo model was used, that are ectopic bone plates which are developed by endochondral ossification, after having implanted demineralized bone particles at 16 days of development, at which time they are constituted by bone tissue. Ectopic bone plates were used with the aim of knowing as gamma radiation indirectly modifies to cellular level the osteoblast differentiation, cells that are involved in the formation and mineralization of bone extracellular matrix. One of the well known effects of gamma radiation is the generation of free radicals

  6. Mathematical Model of Bone Regeneration in a Porous Implant

    Science.gov (United States)

    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.

  7. Magnesium intake mediates the association between bone mineral density and lean soft tissue in elite swimmers.

    Science.gov (United States)

    Matias, Catarina N; Santos, Diana A; Monteiro, Cristina P; Vasco, Ana M; Baptista, Fátima; Sardinha, Luís B; Laires, Maria J; Silva, Analiza M

    2012-01-01

    Magnesium (Mg) deficiency has been associated with bone disorders. Physical activity is also crucial for bone mineralization. Bone mass loss has been observed to be accelerated in subjects with low Mg intake. We aim to understand if Mg intake mediates the association between bone mineral density (BMD) and lean soft tissue (LST) in elite swimmers. Seventeen elite swimmers (eight males; nine females) were evaluated. Bone mineral content, BMD, LST, and fat mass were assessed using dual energy X-ray absorptiometry. Energy and nutrient intake were assessed during a seven-day period and analyzed with Food Processor SQL. Males presented lower values than the normative data for BMD. Mg, phosphorus (P) and vitamin D intake were significantly lower than the recommended daily allowance. A linear regression model demonstrated a significant association between LST and BMD. When Mg intake was included, we observed that this was a significant, independent predictor of BMD, with a significant increase of 24% in the R(2) of the initial predictive model. When adjusted for energy, vitamin D, calcium, and P intake, Mg remained a significant predictor of BMD. In conclusion, young athletes engaged in low impact sports, should pay special attention to Mg intake, given its potential role in bone mineral mass acquisition during growth.

  8. Chitosan-Alginate Biocomposite Containing Fucoidan for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2014-01-01

    Full Text Available Over the last few years, significant research has been conducted in the construction of artificial bone scaffolds. In the present study, different types of polymer scaffolds, such as chitosan-alginate (Chi-Alg and chitosan-alginate with fucoidan (Chi-Alg-fucoidan, were developed by a freeze-drying method, and each was characterized as a bone graft substitute. The porosity, water uptake and retention ability of the prepared scaffolds showed similar efficacy. The pore size of the Chi-Alg and Chi-Alg-fucoidan scaffolds were measured from scanning electron microscopy and found to be 62–490 and 56–437 µm, respectively. In vitro studies using the MG-63 cell line revealed profound cytocompatibility, increased cell proliferation and enhanced alkaline phosphatase secretion in the Chi-Alg-fucoidan scaffold compared to the Chi-Alg scaffold. Further, protein adsorption and mineralization were about two times greater in the Chi-Alg-fucoidan scaffold than the Chi-Alg scaffold. Hence, we suggest that Chi-Alg-fucoidan will be a promising biomaterial for bone tissue regeneration.

  9. Fabrication of Bioceramic Bone Scaffolds for Tissue Engineering

    Science.gov (United States)

    Liu, Fwu-Hsing

    2014-10-01

    In this study, microhydroxyapatite and nanosilica sol were used as the raw materials for fabrication of bioceramic bone scaffold using selective laser sintering technology in a self-developed 3D Printing apparatus. When the fluidity of ceramic slurry is matched with suitable laser processing parameters, a controlled pore size of porous bone scaffold can be fabricated under a lower laser energy. Results shown that the fabricated scaffolds have a bending strength of 14.1 MPa, a compressive strength of 24 MPa, a surface roughness of 725 nm, a pore size of 750 μm, an apparent porosity of 32%, and a optical density of 1.8. Results indicate that the mechanical strength of the scaffold can be improved after heat treatment at 1200 °C for 2 h, while simultaneously increasing surface roughness conducive to osteoprogenitor cell adhesion. MTT method and SEM observations confirmed that bone scaffolds fabricated under the optimal manufacturing process possess suitable biocompatibility and mechanical properties, allowing smooth adhesion and proliferation of osteoblast-like cells. Therefore, they have great potential for development in the field of tissue engineering.

  10. Micro-distribution of uranium in bone after contamination: new insight into its mechanism of accumulation into bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Bourgeois, Damien [ICSM, LHYS, Bagnols-sur-Ceze (France); Burt-Pichat, Brigitte [INSERM, UMR 1033 Lyon (France); Lyon Univ. (France); Le Goff, Xavier [ICSM, L2ME, Bagnols-sur-Ceze (France)

    2015-09-15

    After internal contamination, uranium rapidly distributes in the body; up to 20 % of the initial dose is retained in the skeleton, where it remains for years. Several studies suggest that uranium has a deleterious effect on the bone cell system, but little is known regarding the mechanisms leading to accumulation of uranium in bone tissue. We have performed synchrotron radiation-based micro-X-ray fluorescence (SR μ-XRF) studies to assess the initial distribution of uranium within cortical and trabecular bones in contaminated rats' femurs at the micrometer scale. This sensitive technique with high spatial resolution is the only method available that can be successfully applied, given the small amount of uranium in bone tissue. Uranium was found preferentially located in calcifying zones in exposed rats and rapidly accumulates in the endosteal and periosteal area of femoral metaphyses, in calcifying cartilage and in recently formed bone tissue along trabecular bone. Furthermore, specific localized areas with high accumulation of uranium were observed in regions identified as micro-vessels and on bone trabeculae. These observations are of high importance in the study of the accumulation of uranium in bone tissue, as the generally proposed passive chemical sorption on the surface of the inorganic part (apatite) of bone tissue cannot account for these results. Our study opens original perspectives in the field of exogenous metal bio-mineralization.

  11. Biodegradable Magnesium Screws Accelerate Fibrous Tissue Mineralization at the Tendon-Bone Insertion in Anterior Cruciate Ligament Reconstruction Model of Rabbit

    Science.gov (United States)

    Wang, Jiali; Xu, Jiankun; Fu, Weimin; Cheng, Wenxiang; Chan, Kaiming; Yung, Patrick Shu-hang; Qin, Ling

    2017-01-01

    The incorporation of tendon graft into bone tunnel is one of the most challenging clinical issues in anterior cruciate ligament (ACL) reconstruction. As a biodegradable metal, Mg has appropriate mechanical strength and osteoinductive effects, thus may be a promising alternative to commercialized products used for graft fixation. Therefore, it was hypothesized that Mg based interference screws would promote tendon graft-bone junction healing when compared to Ti screws. Herein, we compared the effects of Mg and Ti screws on tendon graft healing in rabbits with ACL reconstruction via histological, HR-pQCT and mechanical analysis. The histological results indicated that Mg screws significantly improved the graft healing quality via promoting mineralization at the tendon graft enthesis. Besides, Mg screws significantly promoted bone formation in the peri-screw region at the early healing stage. Importantly, Mg screws exhibited excellent corrosion resistance and the degradation of Mg screws did not induce bone tunnel widening. In tensile testing, there were no significant differences in the load to failure, stress, stiffness and absorption energy between Mg and Ti groups due to the failure mode at the midsubstance. Our findings demonstrate that Mg screws can promote tendon graft healing after ACL reconstruction, implying a potential alternative to Ti screws for clinical applications. PMID:28071744

  12. The relationship between the mechanical anisotropy of human cortical bone tissue and its microstructure

    Science.gov (United States)

    Espinoza Orias, Alejandro A.

    Orthopedics research has made significant advances in the areas of biomechanics, bone implants and bone substitute materials. However, to date there is no definitive model to explain the structure-property relationships in bone as a material to enable better implant designs or to develop a true biomechanical analog of bone. The objective of this investigation was to establish a relationship between the elastic anisotropy of cortical bone tissue and its microstructure. Ultrasonic wave propagation was used to measure stiffness coefficients for specimens sectioned along the length of a human femur. The elastic constants were orthotropic and varied with anatomical location. Stiffness coefficients were generally largest at the midshaft and stiffness anisotropy ratios were largest at the distal and proximal ends. These tests were run on four additional human femurs to assess the influence of phenotypic variation, and in most cases, it was found that phenotypes do not exert a significant effect. Stiffness coefficients were shown to be correlated as a power law relation to apparent density, but anisotropy ratios were not. Texture analysis was performed on selected samples to measure the orientation distribution of the bone mineral crystals. Inverse pole figures showed that bone mineral crystals had a preferred crystallographic orientation, coincident with the long axis of the femur, which is its principal loading direction. The degree of preferred orientation was represented in Multiples of a Random Distribution (MRD), and correlated to the anisotropy ratios. Variation in elastic anisotropy was shown to be primarily due to the bone mineral orientation. The results found in this work can be used to incorporate anisotropy into structural analysis for bone as a material.

  13. Repair of segmental bone defect using Totally Vitalized tissue engineered bone graft by a combined perfusion seeding and culture system.

    Directory of Open Access Journals (Sweden)

    Lin Wang

    Full Text Available BACKGROUND: The basic strategy to construct tissue engineered bone graft (TEBG is to combine osteoblastic cells with three dimensional (3D scaffold. Based on this strategy, we proposed the "Totally Vitalized TEBG" (TV-TEBG which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. METHODS: In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP scaffold fabricated by Rapid Prototyping (RP technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC method, static seeding and perfusion culture (SSPC method, and static seeding and static culture (SSSC method for their in vitro performance and bone defect healing efficacy with a rabbit model. RESULTS: Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. CONCLUSION: This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and

  14. Osteocalcin/fibronectin-functionalized collagen matrices for bone tissue engineering.

    Science.gov (United States)

    Kim, S G; Lee, D S; Lee, S; Jang, J-H

    2015-06-01

    Collagen is the most abundant protein found in the extracellular matrix and is widely used to build scaffolds for biomedical applications which are the result of its biocompatibility and biodegradability. In the present study, we constructed a rhOCN/FNIII9-10 fusion protein and rhOCN/FNIII9-10-functionalized collagen matrices and investigated the potential value for bone tissue engineering. In vitro studies carried out with preosteoblastic MC3T3-E1 cells showed that rhOCN/FNIII9-10 fusion protein promoted cell adhesion and the mRNA levels of osteogenic markers including osteocalcin, runt-related transcription factor 2, alkaline phosphatase (ALP), and collagen type I. In addition, rhOCN/FNIII9-10-functionalized collagen matrices showed significant induction of the ALP activity more than rhFNIII9-10-functionalized collagen matrices or collagen matrices alone. These results suggested that rhOCN/FNIII9-10-functionalized collagen matrices have potential for bone tissue engineering.

  15. Organotypic culture of human bone marrow adipose tissue.

    Science.gov (United States)

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  16. Peculiarities of the bone tissue resorption under microgravity conditions

    Science.gov (United States)

    Rodionova, N.; Oganov, V.; Polkovenko, O.; Nitsevich, T.

    The actual problem - peculiarities of resorptive processes in the spongiose of thingbones - we studied with the use of tranmissive electron microscopy in experiments on rats (American space station SLS-2) and on monkeys Macaca mulatt? (BION-11). Animals were onboard during 2 weeks. There was established, that the resorption happen with osteoclasts participation. They can create groups of cells. In the osteoclasts population we indicated not typical for the control (ground experiment) "giant" cells, which have on ultrathin sections 5-6 nuclei, many lysosomes, well developed "light" zone and "brush-border". The destruction of minera lized matrix in bone lacunas also happens by the way of osteolytic activity of osteocytes. Lysosome ferments of osteocytes are secreted by the eczocytosis. The osteocytic osteolysis, as well as the osteoclastic one can be seen as a physiological, gormon-dependent mechanism of resorption. The presence of a considerable number of neutrophiles, which enter in some zones of resorption is also typical. When these neutrophiles destruct, they release lysosomic ferments that dissolve the bone matrix. In some zones of resorption we noted the presence of the row from collagen fibrils, which loosed crystals , on mineralized matrix borders. The cell detritus is noted in zones of surface dissolving among crystallic conglomerates. It certificates the processes of osteogenic cells destruction that happen here. So, under the microgravity conditions in zones of adaptive remodeling of the spongiose the processes of the bone tissue resorption happen by some ways, namely: by the functional activization of osteoclasts; by the osteocytic osteolysis increasing; as a result of hydrolytic activity of neutrophiles, entering in these zones, and also by the local demineralization and further destruction of bone matrix surface zones.

  17. Tissue engineered humanized bone supports human hematopoiesis in vivo.

    Science.gov (United States)

    Holzapfel, Boris M; Hutmacher, Dietmar W; Nowlan, Bianca; Barbier, Valerie; Thibaudeau, Laure; Theodoropoulos, Christina; Hooper, John D; Loessner, Daniela; Clements, Judith A; Russell, Pamela J; Pettit, Allison R; Winkler, Ingrid G; Levesque, Jean-Pierre

    2015-08-01

    Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  18. Comparative study of cryopreserved bone tissue and tissue preserved in a 98% glycerol solution.

    Science.gov (United States)

    Giovani, Arlete Mazzini Miranda; Croci, Alberto Tesconi; Oliveira, Cláudia Regina G C M; Filippi, Renée Zon; Santos, Luiz Augusto U; Maragni, Graziela G; Albhy, Thays Moreira

    2006-12-01

    To compare the bone graft cryopreservation method (at -80 degrees C) with a preservation method using a 98% glycerol solution at room temperature (10 degrees C-35 degrees C), by testing the antibacterial and fungal effects of 98% glycerol and comparatively analyzing the observed histological changes resulting from the use of both methods. This study was of 30 samples of trabecular bone tissue from 10 patients undergoing total hip arthroplasty. Each femoral head provided 3 samples that were randomized into 3 groups, namely, the control group, the cryopreserved group, and the group preserved in a 98% glycerol at room temperature for 1 year. The samples were submitted to histomorphologic, cell feasibility, and microbiologic analyses. The results were statistically analyzed using the McNemar test, with a statistical significance index of 0.05. Values obtained using the McNemar test to compare probability distributions of histomorphologic variables (mature or lamellar bone, immature bone, and necrosis) and cell feasibility (osteoblasts and osteoclasts) indicated that there is no difference between the distributions of variables under the 3 experimental conditions. Microbiological analysis of the 98% glycerol solution and bone fragments from samples stored for 1 year at room temperature did not show bacterial or fungal growth. The histological and microbiological investigation were performed at 2 different time points: immediately after the sample processing and after 1 year. The method used to preserve bone grafts kept in 98% glycerol at room temperature (10 degrees C-35 degrees C) was similar to cryopreservation in terms of bone matrix preservation; no bacteria or fungi were found in the samples.

  19. 3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering.

    Science.gov (United States)

    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.

  20. Comparison of manual and automated cultures of bone marrow stromal cells for bone tissue engineering.

    Science.gov (United States)

    Akiyama, Hirokazu; Kobayashi, Asako; Ichimura, Masaki; Tone, Hiroshi; Nakatani, Masaru; Inoue, Minoru; Tojo, Arinobu; Kagami, Hideaki

    2015-11-01

    The development of an automated cell culture system would allow stable and economical cell processing for wider clinical applications in the field of regenerative medicine. However, it is crucial to determine whether the cells obtained by automated culture are comparable to those generated by manual culture. In the present study, we focused on the primary culture process of bone marrow stromal cells (BMSCs) for bone tissue engineering and investigated the feasibility of its automation using a commercially available automated cell culture system in a clinical setting. A comparison of the harvested BMSCs from manual and automated cultures using clinically acceptable protocols showed no differences in cell yields, viabilities, surface marker expression profiles, and in vivo osteogenic abilities. Cells cultured with this system also did not show malignant transformation and the automated process was revealed to be safe in terms of microbial contamination. Taken together, the automated procedure described in this report provides an approach to clinical bone tissue engineering. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Comparative study on seeding methods of human bone marrow stromal cells in bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    齐欣; 刘建国; 常颖; 徐莘香

    2004-01-01

    Background In general the traditional static seeding method has its limitation while the dynamic seeding method reveals its advantages over traditional static method. We compared static and dynamic seeding method for human bone marrow stromal cells (hBMSCs) in bone tissue engineering.Methods DNA assay was used for detecting the maximal initial seeding concentration for static seeding. Dynamic and static seeding methods were compared, when scaffolds were loaded with hBMSCs at this maximal initial cell seeding concentration. Histology and scanning electron microscope (SEM) were examined to evaluate the distribution of cells inside the constructs. Markers encoding osteogenic genes were measured by fluorescent RT-PCR. The protocol for dynamic seeding of hBMSCs was also investigated.Results DNA assay showed that the static maximal initial seeding concentration was lower than that in dynamic seeding. Histology and SEM showed even distribution and spread of cells in the dynamically seeded constructs, while their statically seeded counterparts showed cell aggregation.Fluorescent RT-PCR again showed stronger osteogenic potential of dynamically seeded constructs.Conclusion dynamic seeding of hBMSCs is a promising technique in bone tissue engineering.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    2015-12-01

    and an “outer” layer (thicker, fibrous, mechanically robust, and less vascular. Samples for cell and CTP analysis are minced and digested in...Sternum autograft cancellous bone graft (ACBG) histology A scoring system for ACBG histology has been developed to define areas of hematopoietic marrow...D’Alleyrand) Dr. D’Alleyrand had continued his interaction with Drs. Pluhar and Muschler and the veterinary staff at Cleveland Clinic during the animal

  4. Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    2014-10-01

    Subjacent to this narrow zone, the tissue is composed of granulation tissue that extends to the outermost margin of the section. All samples...the epidermal growth factor family. VWF Encodes a glycoprotein which functions as an antihemophilic factor carrier and a platelet -vessel wall mediator...in the blood coagulation system. It is crucial to the hemostasis process. PDGFB Protein encoded by this gene is a member of the platelet -derived

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. Early tissue responses to zoledronate, locally delivered by bone screw, into a compromised cancellous bone site: a pilot study

    National Research Council Canada - National Science Library

    Arnoldi, Joerg; Alves, Antoine; Procter, Philip

    2014-01-01

    ...) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described...

  10. Low temperature setting polymer-ceramic composites for bone tissue engineering

    Science.gov (United States)

    Sethuraman, Swaminathan

    Tissue engineering is defined as "the application of biological, chemical and engineering principles towards the repair, restoration or regeneration of tissues using scaffolds, cells, factors alone or in combination". The hypothesis of this thesis is that a matrix made of a synthetic biocompatible, biodegradable composite can be designed to mimic the properties of bone, which itself is a composite. The overall goal was to design and develop biodegradable, biocompatible polymer-ceramic composites that will be a practical alternative to current bone repair materials. The first specific aim was to develop and evaluate the osteocompatibility of low temperature self setting calcium deficient apatites for bone tissue engineering. The four different calcium deficient hydroxyapatites evaluated were osteocompatible and expressed the characteristic genes for osteoblast proliferation, maturation, and differentiation. Our next objective was to develop and evaluate the osteocompatibility of biodegradable amino acid ester polyphosphazene in vitro as candidates for forming composites with low temperature apatites. We determined the structure-property relationship, the cellular adhesion, proliferation, and differentiation of primary rat osteoblast cells on two dimensional amino acid ester based polyphosphazene films. Our next goal was to evaluate the amino acid ester based polyphosphazenes in a subcutaneous rat model and our results demonstrated that the polyphosphazenes evaluated in the study were biocompatible. The physio-chemical property characterization, cellular response and gene expression on the composite surfaces were evaluated. The results demonstrated that the precursors formed calcium deficient hydroxyapatite in the presence of biodegradable polyphosphazenes. In addition, cells on the surface of the composites expressed normal phenotype and characteristic genes such as type I collagen, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein. The in vivo

  11. Brazilian minipig as a large-animal model for basic research and stem cell-based tissue engineering. Characterization and in vitro differentiation of bone marrow-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Roberta Targa STRAMANDINOLI-ZANICOTTI

    2014-06-01

    Full Text Available Stem cell-based regenerative medicine is one of the most intensively researched medical issues. Pre-clinical studies in a large-animal model, especially in swine or miniature pigs, are highly relevant to human applications. Mesenchymal stem cells (MSCs have been isolated and expanded from different sources. Objective: This study aimed at isolating and characterizing, for the first time, bone marrow-derived MSCs (BM-MSCs from a Brazilian minipig (BR1. Also, this aimed to validate a new large-animal model for stem cell-based tissue engineering. Material and Methods: Bone marrow (BM was aspirated from the posterior iliac crest of twelve adult male BR1 under general anesthesia. MSCs were selected by plastic-adherence as originally described by Friedenstein. Cell morphology, surface marker expression, and cellular differentiation were examined. The immunophenotypic profile was determined by flow cytometry. The differentiation potential was assessed by cytological staining and by RT-PCR. Results: MSCs were present in all minipig BM samples. These cells showed fibroblastic morphology and were positive for the surface markers CD90 (88.6%, CD29 (89.8%, CD44 (86.9% and negative for CD34 (1.61%, CD45 (1.83%, CD14 (1.77% and MHC-II (2.69%. MSCs were differentiated into adipocytes, osteoblasts, and chondroblasts as demonstrated by the presence of lipidic-rich vacuoles, the mineralized extracellular matrix, and the great presence of glycosaminoglycans, respectively. The higher gene expression of adipocyte fatty-acid binding protein (AP2, alkaline phosphatase (ALP and collagen type 2 (COLII also confirmed the trilineage differentiation (p<0.001, p<0.001, p=0.031; respectively. Conclusions: The isolation, cultivation, and differentiation of BM-MSCs from BR1 makes this animal eligible as a useful large-animal model for stem cell-based studies in Brazil.

  12. Calcium Phosphate Scaffolds Combined with Bone Morphogenetic Proteins or Mesenchymal Stem Cells in Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Han Sun

    2015-01-01

    Full Text Available Objective: The purpose of this study was to review the current status of calcium phosphate (CaP scaffolds combined with bone morphogenetic proteins (BMPs or mesenchymal stem cells (MSCs in the field of bone tissue engineering (BTE. Date Sources: Data cited in this review were obtained primarily from PubMed and Medline in publications from 1979 to 2014, with highly regarded older publications also included. The terms BTE, CaP, BMPs, and MSC were used for the literature search. Study Selection: Reviews focused on relevant aspects and original articles reporting in vitro and/or in vivo results concerning the efficiency of CaP/BMPs or CaP/MSCs composites were retrieved, reviewed, analyzed, and summarized. Results: An ideal BTE product contains three elements: Scaffold, growth factors, and stem cells. CaP-based scaffolds are popular because of their outstanding biocompatibility, bioactivity, and osteoconductivity. However, they lack stiffness and osteoinductivity. To solve this problem, composite scaffolds of CaP with BMPs have been developed. New bone formation by CaP/BMP composites can reach levels similar to those of autografts. CaP scaffolds are compatible with MSCs and CaP/MSC composites exhibit excellent osteogenesis and stiffness. In addition, a CaP/MSC/BMP scaffold can repair bone defects more effectively than an autograft. Conclusions: Novel BTE products possess remarkable osteoconduction and osteoinduction capacities, and exhibit balanced degradation with osteogenesis. Further work should yield safe, viable, and efficient materials for the repair of bone lesions.

  13. Calcium Phosphate Scaffolds Combined with Bone Morphogenetic Proteins or Mesenchymal Stem Cells in Bone Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Han Sun; Hui-Lin Yang

    2015-01-01

    Objective:The purpose of this study was to review the current status of calcium phosphate (CaP) scaffolds combined with bone morphogenetic proteins (BMPs) or mesenchymal stem cells (MSCs) in the field of bone tissue engineering (BTE).Date Sources:Data cited in this review were obtained primarily from PubMed and Medline in publications from 1979 to 2014,with highly regarded older publications also included.The terms BTE,CaP,BMPs,and MSC were used for the literature search.Study Selection:Reviews focused on relevant aspects and original articles reporting in vitro and/or in vivo results concerning the efficiency of CaP/BMPs or CaP/MSCs composites were retrieved,reviewed,analyzed,and summarized.Results:An ideal BTE product contains three elements:Scaffold,growth factors,and stem cells.CaP-based scaffolds are popular because of their outstanding biocompatibility,bioactivity,and osteoconductivity.However,they lack stiffness and osteoinductivity.To solve this problem,composite scaffolds of CaP with BMPs have been developed.New bone formation by CaP/BMP composites can reach levels similar to those of autografts.CaP scaffolds are compatible with MSCs and CaP/MSC composites exhibit excellent osteogenesis and stiffness.In addition,a CaP/MSC/BMP scaffold can repair bone defects more effectively than an autograft.Conclusions:Novel BTE products possess remarkable osteoconduction and osteoinduction capacities,and exhibit balanced degradation with osteogenesis.Further work should yield safe,viable,and efficient materials for the repair of bone lesions.

  14. Statistical shape and appearance models of bones.

    Science.gov (United States)

    Sarkalkan, Nazli; Weinans, Harrie; Zadpoor, Amir A

    2014-03-01

    When applied to bones, statistical shape models (SSM) and statistical appearance models (SAM) respectively describe the mean shape and mean density distribution of bones within a certain population as well as the main modes of variations of shape and density distribution from their mean values. The availability of this quantitative information regarding the detailed anatomy of bones provides new opportunities for diagnosis, evaluation, and treatment of skeletal diseases. The potential of SSM and SAM has been recently recognized within the bone research community. For example, these models have been applied for studying the effects of bone shape on the etiology of osteoarthritis, improving the accuracy of clinical osteoporotic fracture prediction techniques, design of orthopedic implants, and surgery planning. This paper reviews the main concepts, methods, and applications of SSM and SAM as applied to bone.

  15. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia.

    Science.gov (United States)

    Bonetto, Andrea; Kays, Joshua K; Parker, Valorie A; Matthews, Ryan R; Barreto, Rafael; Puppa, Melissa J; Kang, Kyung S; Carson, James A; Guise, Theresa A; Mohammad, Khalid S; Robling, Alexander G; Couch, Marion E; Koniaris, Leonidas G; Zimmers, Teresa A

    2016-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and Apc(Min/+). The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the Apc(Min/+) mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia.

  16. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia

    Science.gov (United States)

    Bonetto, Andrea; Kays, Joshua K.; Parker, Valorie A.; Matthews, Ryan R.; Barreto, Rafael; Puppa, Melissa J.; Kang, Kyung S.; Carson, James A.; Guise, Theresa A.; Mohammad, Khalid S.; Robling, Alexander G.; Couch, Marion E.; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2017-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia. PMID:28123369

  17. Computational modeling of epithelial tissues.

    Science.gov (United States)

    Smallwood, Rod

    2009-01-01

    There is an extensive literature on the computational modeling of epithelial tissues at all levels from subcellular to whole tissue. This review concentrates on behavior at the individual cell to whole tissue level, and particularly on organizational aspects, and provides an indication of where information from other areas, such as the modeling of angiogenesis, is relevant. The skin, and the lining of all of the body cavities (lung, gut, cervix, bladder etc) are epithelial tissues, which in a topological sense are the boundary between inside and outside the body. They are thin sheets of cells (usually of the order of 0.5 mm thick) without extracellular matrix, have a relatively simple structure, and contain few types of cells. They have important barrier, secretory and transport functions, which are essential for the maintenance of life, so homeostasis and wound healing are important aspects of the behavior of epithelial tissues. Carcinomas originate in epithelial tissues.There are essentially two approaches to modeling tissues--to start at the level of the tissue (i.e., a length scale of the order of 1 mm) and develop generalized equations for behavior (a continuum approach); or to start at the level of the cell (i.e., a length scale of the order of 10 µm) and develop tissue behavior as an emergent property of cellular behavior (an individual-based approach). As will be seen, these are not mutually exclusive approaches, and they come in a variety of flavors.

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

    Directory of Open Access Journals (Sweden)

    Antonio Boccaccio

    Full Text Available 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

  19. Single walled carbon nanotube composites for bone tissue engineering.

    Science.gov (United States)

    Gupta, Ashim; Woods, Mia D; Illingworth, Kenneth David; Niemeier, Ryan; Schafer, Isaac; Cady, Craig; Filip, Peter; El-Amin, Saadiq F

    2013-09-01

    The purpose of this study was to develop single walled carbon nanotubes (SWCNT) and poly lactic-co-glycolic acid (PLAGA) composites for orthopedic applications and to evaluate the interaction of human stem cells (hBMSCs) and osteoblasts (MC3T3-E1 cells) via cell growth, proliferation, gene expression, extracellular matrix production and mineralization. PLAGA and SWCNT/PLAGA composites were fabricated with various amounts of SWCNT (5, 10, 20, 40, and 100 mg), characterized and degradation studies were performed. Cells were seeded and cell adhesion/morphology, growth/survival, proliferation and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated uniform incorporation of SWCNT into the PLAGA matrix and addition of SWCNT did not affect the degradation rate. Imaging studies revealed that MC3T3-E1 and hBMSCs cells exhibited normal, non-stressed morphology on the composites and all were biocompatible. Composites with 10 mg SWCNT resulted in highest rate of cell proliferation (p composites. Gene expression of alkaline phosphatase, collagen I, osteocalcin, osteopontin, Runx-2, and Bone Sialoprotein was observed on all composites. In conclusion, SWCNT/PLAGA composites imparted beneficial cellular growth capabilities and gene expression, and mineralization abilities were well established. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration and bone tissue engineering (BTE) and are promising for orthopedic applications.

  20. Bone and soft tissue tumors of hip and pelvis

    Energy Technology Data Exchange (ETDEWEB)

    Bloem, Johan L., E-mail: j.l.bloem@lumc.nl [Leiden University Medical Center, Department of Radiology, PO Box 9600, 2300 RC Leiden (Netherlands); Reidsma, Inge I., E-mail: i.i.reidsma@lumc.nl [Leiden University Medical Center, Department of Radiology, PO Box 9600, 2300 RC Leiden (Netherlands)

    2012-12-15

    Objective is to identify epidemiologic and radiologic criteria allowing specific diagnoses of tumors and tumor-like lesions in the hip region and pelvis, and to optimize pre-operative staging. Patients with pelvic tumors are usually older, and their tumors are larger relative to patients with tumors in extremities. The majority of tumors in the pelvis are malignant (metastases, myeloma, chondrosarcoma, Ewing-, osteo-, and MFH/fibrosarcoma), while those in the proximal femur are in majority benign (fibrous dysplasia, solitary bone cyst, and osteoid osteoma). Soft tissue masses in the thigh in the elderly are typically sarcomas without tumor specific signs. Common tumor-like lesions occurring in the hip and pelvis that can mimic neoplasm are: infections (including tuberculosis), insufficiency/avulsion fractures, cysts, fibrous dysplasia, aneurysmal bone cyst, Langerhans cell histiocytosis, and Paget's disease. Local MR staging is based on the compartmental anatomy. The psoas and gluteal muscles are easily invaded by sarcoma originating in the ileum. The pectineus muscle protects the neurovascular bundle at the level of the hip. The thigh is separated into three compartments, some structures (Sartorius muscle) cross borders between compartments. Immobile joints (SI-joints, osteoarthritic hip) are relatively easily crossed by sarcoma and giant cell tumor.

  1. Cobalt doped proangiogenic hydroxyapatite for bone tissue engineering application.

    Science.gov (United States)

    Kulanthaivel, Senthilguru; Roy, Bibhas; Agarwal, Tarun; Giri, Supratim; Pramanik, Krishna; Pal, Kunal; Ray, Sirsendu S; Maiti, Tapas K; Banerjee, Indranil

    2016-01-01

    The present study delineates the synthesis and characterization of cobalt doped proangiogenic-osteogenic hydroxyapatite. Hydroxyapatite samples, doped with varying concentrations of bivalent cobalt (Co(2+)) were prepared by the ammoniacal precipitation method and the extent of doping was measured by ICP-OES. The crystalline structure of the doped hydroxyapatite samples was confirmed by XRD and FTIR studies. Analysis pertaining to the effect of doped hydroxyapatite on cell cycle progression and proliferation of MG-63 cells revealed that the doping of cobalt supported the cell viability and proliferation up to a threshold limit. Furthermore, such level of doping also induced differentiation of the bone cells, which was evident from the higher expression of differentiation markers (Runx2 and Osterix) and better nodule formation (SEM study). Western blot analysis in conjugation with ELISA study confirmed that the doped HAp samples significantly increased the expression of HIF-1α and VEGF in MG-63 cells. The analysis described here confirms the proangiogenic-osteogenic properties of the cobalt doped hydroxyapatite and indicates its potential application in bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Meshless methods in biomechanics bone tissue remodelling analysis

    CERN Document Server

    Belinha, Jorge

    2014-01-01

    This book presents the complete formulation of a new advanced discretization meshless technique: the Natural Neighbour Radial Point Interpolation Method (NNRPIM). In addition, two of the most popular meshless methods, the EFGM and the RPIM, are fully presented. Being a truly meshless method, the major advantages of the NNRPIM over the FEM, and other meshless methods, are the remeshing flexibility and the higher accuracy of the obtained variable field. Using the natural neighbour concept, the NNRPIM permits to determine organically the influence-domain, resembling the cellulae natural behaviour. This innovation permits the analysis of convex boundaries and extremely irregular meshes, which is an advantage in the biomechanical analysis, with no extra computational effort associated.   This volume shows how to extend the NNRPIM to the bone tissue remodelling analysis, expecting to contribute with new numerical tools and strategies in order to permit a more efficient numerical biomechanical analysis.

  3. Rapid prototyping for tissue-engineered bone scaffold by 3D printing and biocompatibility study.

    Science.gov (United States)

    He, Hui-Yu; Zhang, Jia-Yu; Mi, Xue; Hu, Yang; Gu, Xiao-Yu

    2015-01-01

    The prototyping of tissue-engineered bone scaffold (calcined goat spongy bone-biphasic ceramic composite/PVA gel) by 3D printing was performed, and the biocompatibility of the fabricated bone scaffold was studied. Pre-designed STL file was imported into the GXYZ303010-XYLE 3D printing system, and the tissue-engineered bone scaffold was fabricated by 3D printing using gel extrusion. Rabbit bone marrow stromal cells (BMSCs) were cultured in vitro and then inoculated to the sterilized bone scaffold obtained by 3D printing. The growth of rabbit BMSCs on the bone scaffold was observed under the scanning electron microscope (SEM). The effect of the tissue-engineered bone scaffold on the proliferation and differentiation of rabbit BMSCs using MTT assay. Universal testing machine was adopted to test the tensile strength of the bone scaffold. The leachate of the bone scaffold was prepared and injected into the New Zealand rabbits. Cytotoxicity test, acute toxicity test, pyrogenic test and intracutaneous stimulation test were performed to assess the biocompatibility of the bone scaffold. Bone scaffold manufactured by 3D printing had uniform pore size with the porosity of about 68.3%. The pores were well interconnected, and the bone scaffold showed excellent mechanical property. Rabbit BMSCs grew and proliferated on the surface of the bone scaffold after adherence. MTT assay indicated that the proliferation and differentiation of rabbit BMSCs on the bone scaffold did not differ significantly from that of the cells in the control. In vivo experiments proved that the bone scaffold fabricated by 3D printing had no acute toxicity, pyrogenic reaction or stimulation. Bone scaffold manufactured by 3D printing allows the rabbit BMSCs to adhere, grow and proliferate and exhibits excellent biomechanical property and high biocompatibility. 3D printing has a good application prospect in the prototyping of tissue-engineered bone scaffold.

  4. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    Science.gov (United States)

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  5. Brazilian minipig as a large-animal model for basic research and stem cell-based tissue engineering. Characterization and in vitro differentiation of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Stramandinoli-Zanicotti, Roberta Targa; Carvalho, André Lopes; Rebelatto, Carmen Lúcia Kuniyoshi; Sassi, Laurindo Moacir; Torres, Maria Fernanda; Senegaglia, Alexandra Cristina; Boldrinileite, Lidiane Maria; Correa-Dominguez, Alejandro; Kuligovsky, Crisciele; Brofman, Paulo Roberto Slud

    2014-06-01

    Stem cell-based regenerative medicine is one of the most intensively researched medical issues. Pre-clinical studies in a large-animal model, especially in swine or miniature pigs, are highly relevant to human applications. Mesenchymal stem cells (MSCs) have been isolated and expanded from different sources. This study aimed at isolating and characterizing, for the first time, bone marrow-derived MSCs (BM-MSCs) from a Brazilian minipig (BR1). Also, this aimed to validate a new large-animal model for stem cell-based tissue engineering. Bone marrow (BM) was aspirated from the posterior iliac crest of twelve adult male BR1 under general anesthesia. MSCs were selected by plastic-adherence as originally described by Friedenstein. Cell morphology, surface marker expression, and cellular differentiation were examined. The immunophenotypic profile was determined by flow cytometry. The differentiation potential was assessed by cytological staining and by RT-PCR. MSCs were present in all minipig BM samples. These cells showed fibroblastic morphology and were positive for the surface markers CD90 (88.6%), CD29 (89.8%), CD44 (86.9%) and negative for CD34 (1.61%), CD45 (1.83%), CD14 (1.77%) and MHC-II (2.69%). MSCs were differentiated into adipocytes, osteoblasts, and chondroblasts as demonstrated by the presence of lipidic-rich vacuoles, the mineralized extracellular matrix, and the great presence of glycosaminoglycans, respectively. The higher gene expression of adipocyte fatty-acid binding protein (AP2), alkaline phosphatase (ALP) and collagen type 2 (COLII) also confirmed the trilineage differentiation (pcell-based studies in Brazil.

  6. Computational Modeling in Tissue Engineering

    CERN Document Server

    2013-01-01

    One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in:  (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each...

  7. A sugar-based phase-transitioning delivery system for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    TL Cheng

    2013-10-01

    Full Text Available Bone tissue engineering approaches commonly involve the delivery of recombinant human bone morphogenetic proteins (rhBMPs. However, there are limitations associated with the currently used carriers, including the need for surgical implantation and the associated increase in infection risk. As an alternative to traditional porous collagen sponge, we have adopted a solution of the injectable sucrose acetate isobutyrate (SAIB as a carrier for rhBMP-2. The ability to deliver rhBMP-2 and other agents by injection reduces the infection risk and lesion size whilst in surgery, with the potential to avoid open surgery altogether in some indications.The primary methodology used for this in vivo study was a C57BL6/J mouse ectopic bone formation model. Specimens were examined by x-ray, microCT, and histology at 3 weeks. SAIB was delivered non-invasively and produced up to 3-fold greater bone volume compared to collagen. To further refine and improve upon the formulation, SAIB containing rhBMP-2 was admixed with candidate compounds including ceramic microparticles, anti-resorptives, and cell signalling inhibitors and further tested in vivo. The formulation combining SAIB/rhBMP-2, the bisphosphonate zoledronic acid (ZA, and hydroxyapatite (HA microparticles yielded a 10-fold greater bone volume than SAIB/rhBMP-2 alone. To investigate the mechanism underlying the synergy between ZA and HA, we used in vitro binding assays and in vivo fluorescent biodistribution studies to demonstrate that ceramic particles could bind and sequester the bisphosphonate. These data show the utility of SAIB as a non-invasive rhBMP delivery system as well as describing an optimised formulation for bone tissue engineering.

  8. Osteogenic Effects of Dedifferentiated Fat Cell Transplantation in Rabbit Models of Bone Defect and Ovariectomy-Induced Osteoporosis

    OpenAIRE

    Kikuta, Shinsuke; Tanaka, Nobuaki; Kazama, Tomohiko; Kazama, Minako; Kano, Koichiro; Ryu, Junnosuke; Tokuhashi, Yasuaki; Matsumoto, Taro

    2013-01-01

    We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was obser...

  9. An update on the Application of Nanotechnology in Bone Tissue Engineering

    Science.gov (United States)

    Griffin, MF; Kalaskar, DM; Seifalian, A.; Butler, PE

    2016-01-01

    Background: 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. Methods: 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. Results: 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. Conclusion: Future studies to improve the application of nanomaterials for bone tissue engineering are needed. PMID:28217209

  10. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

    Directory of Open Access Journals (Sweden)

    Quarto Rodolfo

    2010-01-01

    Full Text Available Abstract Background Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. Methods We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. Results At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. Conclusions We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

  11. Clinical application of human mesenchymal stromal cells for bone tissue engineering

    NARCIS (Netherlands)

    Ganguly, Anindita; Meijer, Gert; van Blitterswijk, Clemens; de Boer, Jan

    2010-01-01

    The gold standard in the repair of bony defects is autologous bone grafting, even though it has drawbacks in terms of availability and morbidity at the harvesting site. Bone-tissue engineering, in which osteogenic cells and scaffolds are combined, is considered as a potential bone graft substitute

  12. Routine bone scintigraphy in primary staging of soft tissue sarcoma - Is it worthwhile?

    NARCIS (Netherlands)

    Jager, PL; Hoekstra, HJ; Leeuw, JA; van der Graaf, WTA; de Vries, EGE; Piers, DA

    2000-01-01

    BACKGROUND. The incidence of bone metastases in soft tissue sarcoma (STS) patients seems to be low but has not been studied separately. In this study, the authors aimed to determine the value of routine radionuclide bone scanning in preoperative staging of STS patients. METHODS. Preoperative bone

  13. Routine bone scintigraphy in primary staging of soft tissue sarcoma - Is it worthwhile?

    NARCIS (Netherlands)

    Jager, PL; Hoekstra, HJ; Leeuw, JA; van der Graaf, WTA; de Vries, EGE; Piers, DA

    2000-01-01

    BACKGROUND. The incidence of bone metastases in soft tissue sarcoma (STS) patients seems to be low but has not been studied separately. In this study, the authors aimed to determine the value of routine radionuclide bone scanning in preoperative staging of STS patients. METHODS. Preoperative bone sc

  14. Hybrid Matrix Grafts to Favor Tissue Regeneration in Rabbit Femur Bone Lesions

    Science.gov (United States)

    Goy, Dante Pascual; Gorosito, Emmanuel; Costa, Hermes S; Mortarino, Pablo; Pedemonte, Noelia Acosta; Toledo, Javier; Mansur, Herman S; Pereira, Marivalda M; Battaglino, Ricardo; Feldman, Sara

    2012-01-01

    At present, typical approaches employed to repair fractures and other bone lesions tend to use matrix grafts to promote tissue regeneration. These grafts act as templates, which promote cellular adhesion, growth and proliferation, osteoconduction, and even osteoinduction, which commonly results in de novo osteogenesis. The present work aimed to study the bone-repairing ability of hybrid matrixes (HM) prepared with polyvinyl alcohol (PVA) and bioactive glass in an experimental rabbit model. The HM were prepared by combining 30% bioactive glass (nominal composition of 58% SiO2 -33 % CaO - 9% P2O5) and 70% PVA. New Zealand rabbits were randomly divided into the control group (C group) and two groups with bone lesions, in which one received a matrix implant HM (Implant group), while the other did not (no Implant group). Clinical monitoring showed no altered parameters from either the Implant or the no Implant groups as compared to the control group, for the variables of diet grades, day and night temperatures and hemograms. In the Implant group, radiologic and tomographic studies showed implanted areas with clean edges in femoral non-articular direction, and radio-dense images that suggest incipient integration. Minimum signs of phlogosis could be observed, whereas no signs of rejection at this imaging level could be identified. Histological analysis showed evidence of osteo-integration, with the formation of a trabecular bone within the implant. Together, these results show that implants of hybrid matrixes of bioactive glass are capable of promoting bone regeneration. PMID:22848334

  15. Changes in the population of perivascular cells in the bone tissue remodeling zones under microgravity

    Science.gov (United States)

    Katkova, Olena; Rodionova, Natalia; Shevel, Ivan

    2016-07-01

    Microgravity and long-term hypokinesia induce reduction both in bone mass and mineral saturation, which can lead to the development of osteoporosis and osteopenia. (Oganov, 2003). Reorganizations and adaptive remodeling processes in the skeleton bones occur in the topographical interconnection with blood capillaries and perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel, Fee, 1980; Rodionova, 1989, 2006) have shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic. Hence the study of populations of perivascular stromal cells in areas of destructive changes is actual. Perivascular cells from metaphysis of the rat femoral bones under conditions of modeling microgravity were studied using electron microscopy and cytochemistry (hindlimb unloading, 28 days duration) and biosatellite «Bion-M1» (duration of flight from April 19 till May 19, 2013 on C57, black mice). It was revealed that both control and test groups populations of the perivascular cells are not homogeneous in remodeling adaptive zones. These populations comprise of adjacent to endothelium poorly differentiated forms and isolated cells with signs of differentiation (specific increased volume of rough endoplasmic reticulum in cytoplasm). Majority of the perivascular cells in the control group (modeling microgravity) reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In poorly differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of experimental animals reaction to the alkaline phosphatase is registered not in all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. Under microgravity some poorly differentiated perivascular

  16. Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

    Science.gov (United States)

    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.

  17. Evaluation of minimal disseminated disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients.

    Science.gov (United States)

    Dolmans, M M; Iwahara, Y; Donnez, J; Soares, M; Vaerman, J L; Amorim, C A; Poirel, H

    2016-10-01

    What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? Minimal disseminated disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented

  18. Graphene and its nanostructure derivatives for use in bone tissue engineering: Recent advances.

    Science.gov (United States)

    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.

  19. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  20. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  1. The correlation between mineralization degree and bone tissue stiffness in the porcine mandibular condyle

    NARCIS (Netherlands)

    Willems, N.M.B.K.; Mulder, L.; den Toonder, J.M.J.; Zentner, A.; Langenbach, G.E.J.

    2014-01-01

    The aim of this study was to correlate the local tissue mineral density (TMD) with the bone tissue stiffness. It was hypothesized that these variables are positively correlated. Cancellous and cortical bone samples were derived from ten mandibular condyles taken from 5 young and 5 adult female pigs.

  2. Electrospun Hydroxyapatite-Containing Chitosan Nanofibers Crosslinked with Genipin for Bone Tissue Engineering

    OpenAIRE

    Frohbergh, Michael E.; Katsman, Anna; Botta, Gregory P.; Lazarovici, Phillip; Schauer, Caroline L.; Wegst, Ulrike G.K.; Lelkes, Peter I

    2012-01-01

    Reconstruction of large bone defects remains problematic in orthopedic and craniofacial clinical practice. Autografts are limited in supply and are associated with donor site morbidity while other materials show poor integration with the host’s own bone. This lack of integration is often due to the absence of periosteum, the outer layer of bone that contains osteoprogenitor cells and is critical for the growth and remodeling of bone tissue. In this study we developed a one-step platform to el...

  3. Biomineralization of a Self-Assembled Extracellular Matrix for Bone Tissue Engineering

    OpenAIRE

    Meng, Yizhi; Qin, Yi-Xian; DiMasi, Elaine; Ba, Xiaolan; Rafailovich, Miriam; Pernodet, Nadine

    2008-01-01

    Understanding how biomineralization occurs in the extracellular matrix (ECM) of bone cells is crucial to the understanding of bone formation and the development of a successfully engineered bone tissue scaffold. It is still unclear how ECM mechanical properties affect protein-mineral interactions in early stages of bone mineralization. We investigated the longitudinal mineralization properties of MC3T3-E1 cells and the elastic modulus of their ECM using shear modulation force microscopy, sync...

  4. Biomimetic coatings for bone tissue engineering of critical-sized defects

    OpenAIRE

    2010-01-01

    The repair of critical-sized bone defects is still challenging in the fields of implantology, maxillofacial surgery and orthopaedics. Current therapies such as autografts and allografts are associated with various limitations. Cytokine-based bone tissue engineering has been attracting increasing attention. Bone-inducing agents have been locally injected to stimulate the native bone-formation activity, but without much success. The reason is that these drugs must be delivered slowly and at a l...

  5. Vibration acceleration promotes bone formation in rodent models

    Science.gov (United States)

    Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

    2017-01-01

    All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the

  6. [Current status of bone/cartilage tissue engineering towards clinical applications].

    Science.gov (United States)

    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.

  7. Cobalt doped proangiogenic hydroxyapatite for bone tissue engineering application

    Energy Technology Data Exchange (ETDEWEB)

    Kulanthaivel, Senthilguru [Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769008 (India); Roy, Bibhas [Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302 (India); Agarwal, Tarun [Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769008 (India); Giri, Supratim [Department of Chemistry, National Institute of Technology, Rourkela, Odisha 769008 (India); Pramanik, Krishna; Pal, Kunal; Ray, Sirsendu S. [Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769008 (India); Maiti, Tapas K. [Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302 (India); Banerjee, Indranil, E-mail: indraniliit@gmail.com [Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769008 (India)

    2016-01-01

    ABSTRACT: The present study delineates the synthesis and characterization of cobalt doped proangiogenic–osteogenic hydroxyapatite. Hydroxyapatite samples, doped with varying concentrations of bivalent cobalt (Co{sup 2+}) were prepared by the ammoniacal precipitation method and the extent of doping was measured by ICP–OES. The crystalline structure of the doped hydroxyapatite samples was confirmed by XRD and FTIR studies. Analysis pertaining to the effect of doped hydroxyapatite on cell cycle progression and proliferation of MG-63 cells revealed that the doping of cobalt supported the cell viability and proliferation up to a threshold limit. Furthermore, such level of doping also induced differentiation of the bone cells, which was evident from the higher expression of differentiation markers (Runx2 and Osterix) and better nodule formation (SEM study). Western blot analysis in conjugation with ELISA study confirmed that the doped HAp samples significantly increased the expression of HIF-1α and VEGF in MG-63 cells. The analysis described here confirms the proangiogenic–osteogenic properties of the cobalt doped hydroxyapatite and indicates its potential application in bone tissue engineering. - Highlights: • Cobalt (Co{sup +2}) doped hydroxyapatite (Co-HAp) can be prepared by the wet chemical method. • The concentration of Co{sup +2} influences the physico-chemical properties of HAp. • Co-HAp was found to be biocompatible and osteogenic. • Co-HAp enhanced cellular VEGF secretion through HIF-1α stabilization. • The optimum biological performance of Co-HAp was achieved for 0.33% (w/w) Co{sup +2} doping.

  8. Microscale Material Properties of Bone and the Mineralized Tissues of the Intervertebral Disc-Vertebral Body Interface

    Science.gov (United States)

    Paietta, Rachel C.

    The objective of this dissertation is to understand the influences of material structure on the properties, function and failure of biological connective tissues. Biological interfaces are becoming an increasingly studied system within mechanics and tissue engineering as a model for attaching dissimilar materials. The elastic modulus of bone (≈ 20 GPa) and cartilage (≈ 0.1-1 MPa) differ over orders of magnitude, which should intuitively create high stress concentrations and failure at the interface. Yet, these natural interface systems rarely fail in vivo, and the mechanism by which loads are transferred between tissues has not yet been established. Tissue quality is one major contributor to the mechanical behavior of bone and cartilage, and is defined by properties such as collagen orientation, mineral volume fraction, porosity and tissue geometry. These properties have yet to be established at the bone-cartilage interface in the spine, and the lack of quantitative data on material microstructure and behavior limits treatments and tissue engineering construct design. In this dissertation, second harmonic generation imaging, quantitative backscattered scanning electron imaging and nanoindentation are combined to characterize micrometer scale tissue quality and modulus in both bone and calcified cartilage. These techniques are utilized to: 1) determine the hierarchical micrometer to millimeter scale properties of lamellar bone, 2) quantify changes throughout development and aging at the human intervertebral disc-vertebral body junction, and 3) explore compressive fractures at this interface. This work is the first to provide quantitative data on the mineral volume fraction, collagen orientation and modulus from the same, undecalcified sections of tissue to corroborate tissue structure and mineralization and describe quantitative parameters of the interface. The principal findings from this work indicate that the underlying matrix, or collagen, organization in

  9. Growth hormone stimulates bone healing in a critical-sized bone defect model

    NARCIS (Netherlands)

    Theyse, L. F. H.; Oosterlaken-Dijksterhuis, M. A.; van Doorn, J.; Dhert, W. J. A.; Hazewinkel, H. A. W.

    2006-01-01

    Growth hormone plays an important role in bone metabolism. Treating bone deficits is a major topic in orthopaedic surgery. Our hypothesis was that local continuous growth hormone administration stimulates bone healing in a canine critical-sized bone defect model. Bone formation in the defects was qu

  10. Use of osteoplastic material to guide bone tissue regeneration deffect.

    Science.gov (United States)

    Machavariani, A; Mazmishvili, K; Grdzelidze, T; Menabde, G; Amiranashvili, I

    2011-12-01

    The goal of research was study of restoration processes in jaw-teeth bone defects by application of osteoplastic materials in the experiment. The experiment was performed over 32 white (6-12 month old) rats; the animals were divided into 2 groups; 16 animals were enrolled in the first group; the section was performed in the edge of lower jaw; the lower jaw body was revealed. Under the effect of the dental drilling machine and the # 1 cooling mean by the fissure bohrium (distilled water) the defect of the dimension of 2x2 mm was created; the defect was washed by 0/9% saline to remove the bone sawdust; the wound was sutured tightly, in layers. The second group of the experiment was staffed with 16 animals (main group); the similar bone defect of the size 2 x 2mm was created on the rat's jaw's body. After washing of modeled defect we inserted osteopathic materials PORESORB-TCP crystals with the size of 0,6-1.0 mm the wound was sutured tightly, in layers. After the 3-rd, 15-th, 30-th and 90-th days from the date of operation there was performed X-ray and morphological examination over the animals in the control as well as the main group. The analysis of the examination performed over the experimental materials showed that in the control group in samples taken at 90th day the defects were not completely restored. In the test group in samples taken at 90th day reparative regeneration is confirmed. This is stimulated by the factor that within the main group's animals the defect regeneration process is supported with the osteoplastic material PORESORB-TCP.

  11. 3D Tissue Scaffold Printing On Custom Artificial Bone Applications

    OpenAIRE

    Betül ALDEMİR; DİKİCİ, Serkan; ÖZTÜRK, Şükrü; KAHRAMAN, Ozan; Aylin ŞENDEMİR ÜRKMEZ; Oflaz, Hakan, 1980-

    2015-01-01

    Production of defect-matching scaffolds is the most critical step in custom artificial bone applications. Three dimensional printing (3DP) is one of the best techniques particularly for custom designs on artificial bone applications because of the high controllability and design independency. Our long-term aim is to implant an artificial custom bone that is cultured with patient's own mesenchymal stem cells after determining defect architecture on patient's bone by using CT-scan and printing ...

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

    Science.gov (United States)

    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.

  13. Bone tissue in different parts of the edentulous maxilla and mandible.

    Science.gov (United States)

    Lindhe, Jan; Bressan, Eriberto; Cecchinato, Denis; Corrá, Enrico; Toia, Marco; Liljenberg, Birgitta

    2013-04-01

    The composition of the fully healed edentulous ridge of the posterior maxilla was recently examined and was found to contain about 50% mineralized bone and 16% bone marrow. The objective was to examine the composition of the tissue of the fully healed ridge in different portions of the maxilla and the mandible in partially dentate subjects. Eighty-seven healthy subjects were included. A trephine drill was used to harvest hard tissue specimens. The biopsies were decalcified, embedded in paraffin, sectioned, stained, and examined using a point-counting procedure. The marginal portion of the jaws almost consistently contained a cortical cap that was significantly wider in the mandible than in the maxilla and twice as wide in the anterior as in the posterior segments of the mandible. Lamellar bone and bone marrow were the dominating tissue elements. Lamellar bone occupied about 63% of the tissue in the mandible and 46% in the maxilla. The maxilla contained about 23% bone marrow as compared to 16% in the mandible. In the mandible, 70% (anterior) and 57% (posterior) were made up of lamellar bone. In the maxilla, the proportion of lamellar bone in the anterior and posterior segments was similar (about 45%). Bone marrow occupied close to 40% of the anterior maxilla, while in the posterior maxilla and the anterior and posterior mandible marrow comprised between 13 and 18%. Marked differences existed with respect to tissue composition of the edentulous ridge between the maxilla and the mandible. The cortical crest was wider in the mandible than in the maxilla, and widest in the symphysis region of the mandible. The proportion of bone marrow was greater in the maxilla than in the mandible. The maxillary front tooth region was poor in lamellar bone but rich in bone marrow, while the anterior mandible contained large amounts of mineralized bone but small amounts of bone marrow. © 2012 John Wiley & Sons A/S.

  14. Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

    Directory of Open Access Journals (Sweden)

    D Gothard

    2014-10-01

    Full Text Available There is a growing socio-economic need for effective strategies to repair damaged bone resulting from disease, trauma and surgical intervention. Bone tissue engineering has received substantial investment over the last few decades as a result. A multitude of studies have sought to examine the efficacy of multiple growth factors, delivery systems and biomaterials within in vivo animal models for the repair of critical-sized bone defects. Defect repair requires recapitulation of in vivo signalling cascades, including osteogenesis, chondrogenesis and angiogenesis, in an orchestrated spatiotemporal manner. Strategies to drive parallel, synergistic and consecutive signalling of factors including BMP-2, BMP-7/OP-1, FGF, PDGF, PTH, PTHrP, TGF-β3, VEGF and Wnts have demonstrated improved bone healing within animal models. Enhanced bone repair has also been demonstrated in the clinic following European Medicines Agency and Food and Drug Administration approval of BMP-2, BMP-7/OP-1, PDGF, PTH and PTHrP. The current review assesses the in vivo and clinical data surrounding the application of growth factors for bone regeneration. This review has examined data published between 1965 and 2013. All bone tissue engineering studies investigating in vivo response of the growth factors listed above, or combinations thereof, utilising animal models or human trials were included. All studies were compiled from PubMed-NCBI using search terms including ‘growth factor name’, ‘in vivo’, ‘model/animal’, ‘human’, and ‘bone tissue engineering’. Focus is drawn to the in vivo success of osteoinductive growth factors incorporated within material implants both in animals and humans, and identifies the unmet challenges within the skeletal regenerative area.

  15. Cortical bone tissue resists fatigue fracture by deceleration and arrest of microcrack growth.

    Science.gov (United States)

    Akkus, O; Rimnac, C M

    2001-06-01

    Knowledge of kinetics of fatigue crack growth of microcracks is important so as to understand the dynamics of bone adaptation, remodeling, and the etiology of fatigue-based failures of cortical bone tissue. In this respect, theoretical models (Taylor, J. Biomech., 31 (1998) 587-592; Taylor and Prendergast, Proc. Instn. Mech. Engrs. Part H 211 (1997) 369-375) of microcrack growth in cortical bone have predicted a decreasing microcrack growth rate with increasing microcrack length. However, these predictions have not been observed directly. This study investigated microcrack growth and arrest through observations of surface microcracks during cyclic loading (R=0.1, 50-80MPa) of human femoral cortical bone (male, n=4, age range: 37-40yr) utilizing a video microscopy system. The change in crack length and orientation of eight surface microcracks were measured with the number of fatigue cycles from four specimens. At the applied cyclic stresses, the microcracks propagated and arrested in generally less than 10,000 cycles. The fatigue crack growth rate of all microcracks decreased with increasing crack length following initial identification, consistent with theoretical predictions. The growth rate of the microcracks was observed to be in the range of 5x10(-5) to 5x10(-7)mmcycle(-1). In addition, many of the microcracks were observed not to grow beyond 150 microm and a cyclic stress intensity factor of 0.5MNm(-3/2). The results of this study suggest that cortical bone tissue may resist fracture at the microscale by deceleration of fatigue crack growth and arrest of microcracks.

  16. Preparation and characterization of bionic bone structure chitosan/hydroxyapatite scaffold for bone tissue engineering.

    Science.gov (United States)

    Zhang, Jiazhen; Nie, Jingyi; Zhang, Qirong; Li, Youliang; Wang, Zhengke; Hu, Qiaoling

    2014-01-01

    Three-dimensional oriented chitosan (CS)/hydroxyapatite (HA) scaffolds were prepared via in situ precipitation method in this research. Scanning electron microscopy (SEM) images indicated that the scaffolds with acicular nano-HA had the spoke-like, multilayer and porous structure. The SEM of osteoblasts which were polygonal or spindle-shaped on the composite scaffolds after seven-day cell culture showed that the cells grew, adhered, and spread well. The results of X-ray powder diffractometer and Fourier transform infrared spectrometer showed that the mineral particles deposited in the scaffold had phase structure similar to natural bone and confirmed that particles were exactly HA. In vitro biocompatibility evaluation indicated the composite scaffolds showed a higher degree of proliferation of MC3T3-E1 cell compared with the pure CS scaffolds and the CS/HA10 scaffold was the highest one. The CS/HA scaffold also had a higher ratio of adhesion and alkaline phosphate activity value of osteoblasts compared with the pure CS scaffold, and the ratio increased with the increase of HA content. The ALP activity value of composite scaffolds was at least six times of the pure CS scaffolds. The results suggested that the composite scaffolds possessed good biocompatibility. The compressive strength of CS/HA15 increased by 33.07% compared with the pure CS scaffold. This novel porous scaffold with three-dimensional oriented structure might have a potential application in bone tissue engineering.

  17. Controlled multiple growth factor delivery from bone tissue engineering scaffolds via designed affinity.

    Science.gov (United States)

    Suárez-González, Darilis; Lee, Jae Sung; Diggs, Alisha; Lu, Yan; Nemke, Brett; Markel, Mark; Hollister, Scott J; Murphy, William L

    2014-08-01

    It is known that angiogenesis plays an important role in bone regeneration and that release of angiogenic and osteogenic growth factors can enhance bone formation. Multiple growth factors play key roles in processes that lead to tissue formation/regeneration during natural tissue development and repair. Therefore, treatments aiming to mimic tissue regeneration can benefit from multiple growth factor release, and there remains a need for simple clinically relevant approaches for dual growth factor release. We hypothesized that mineral coatings could be used as a platform for controlled incorporation and release of multiple growth factors. Specifically, mineral-coated scaffolds were "dip coated" in multiple growth factor solutions, and growth factor binding and release were dictated by the growth factor-mineral binding affinity. Beta tricalcium phosphate (β-TCP) scaffolds were fabricated using indirect solid-free form fabrication techniques and coated with a thin conformal mineral layer. Mineral-coated β-TCP scaffolds were sequentially dipped in recombinant human vascular endothelial growth factor (rhVEGF) and a modular bone morphogenetic peptide, a mineral-binding version of bone morphogenetic protein 2 (BMP2), solutions to allow for the incorporation of each growth factor. The dual release profile showed sustained release of both growth factors for over more than 60 days. Scaffolds releasing either rhVEGF alone or the combination of growth factors showed an increase in blood vessel ingrowth in a dose-dependent manner in a sheep intramuscular implantation model. This approach demonstrates a "modular design" approach, in which a controllable biologics carrier is integrated into a structural scaffold as a thin surface coating.

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

    Science.gov (United States)

    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.

  19. Tissue-engineered bone grafts for osteoplasty in patients with cleft alveolus.

    Science.gov (United States)

    Pradel, Winnie; Lauer, Günter

    2012-11-01

    Alveolar bone grafting is an integral part of the treatment concept in cleft palate patients. As an alternative to autogenous bone, tissue-engineered grafts have found some clinical application. The aim of the present study has been to compare ossification in the cleft area using tissue-engineered grafts in a case series of patients with ossification after transplantation of autogenous spongious bone as the gold standard in alveoloplasty. Eight children with complete cleft lips and cleft palates were included in the study. In four children (group A), the cleft defect was filled with tissue-engineered bone (autogenous osteoblasts cultured on demineralized bone matrix Osteovit(®)); as control in another 4 children (group B), the alveoloplasty was performed using spongious iliac bone. Preoperative and 6 months postoperative cone-beam computed tomography was performed, and volumes of the remaining cleft defects were calculated using 3D navigation software. Wound healing was uneventful in both groups. Six months postoperatively the mean volume of the cleft was 0.55±0.24cm(3) after grafting of tissue-engineered bone (group A) and 0.59±0.23cm(3) after transplantation of autogenous spongiosa. In group A, 40.9% of the cleft defect was ossified; in the control group (group B), 36.6%. Tissue-engineered bone is a promising alternative in alveolar bone grafting and no disadvantages were observed in comparison to the gold standard. Copyright © 2012 Elsevier GmbH. All rights reserved.

  20. Ovalbumin-BasedPorous Scaffolds for Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Gabrielle Farrar

    2010-01-01

    Full Text Available Cell differentiation on glutaraldehyde cross-linked ovalbumin scaffolds was the main focus of this research. Salt leaching and freeze drying were used to create a three-dimensional porous structure. Average pore size was 147.84±40.36 μm and 111.79±30.71 μm for surface and cross sectional area, respectively. Wet compressive strength and elastic modulus were 6.8±3.6 kPa. Average glass transition temperature was 320.1±1.4°C. Scaffolds were sterilized with ethylene oxide prior to seeding MC3T3-E1 cells. Cells were stained with DAPI and Texas red to determine morphology and proliferation. Average cell numbers increased between 4-hour- and 96-hour-cultured scaffolds. Alkaline phosphatase and osteocalcin levels were measured at 3, 7, 14, and 21 days. Differentiation studies showed an increase in osteocalcin at 21 days and alkaline phosphatase levels at 14 days, both indicating differentiation occurred. This work demonstrated the use of ovalbumin scaffolds for a bone tissue engineering application.

  1. Aligned and random nanofibrous nanocomposite scaffolds for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Amir Doustgani

    2013-01-01

    Full Text Available Abstract  Aligned and random nanocomposite nanofibrous scaffolds were electrospun from polycaprolactone (PCL, poly (vinyl alcohol (PVA and hydroxyapatite nanoparticles (nHA. The morphology and mechanical characteristics of the nanofibers were evaluated using scanning electron microscopy and tensile testing, respectively. Scanning electron microscopy revealed fibers with an average diameter of 123 ± 32 nm and 339 ± 107 nm for aligned and random nanofibers, respectively. The mechanical data indicated the higher tensile strength and elastic modulus of aligned nanofibers. The in vitro biocompatibility of aligned and random nanofibrous scaffolds was also assessed by growing mesenchymal stem cells (MSCs, and investigating the proliferation and alkaline phosphatase activity (ALP on different nanofibrous scaffolds. Our  findings  showed  that  the  alignment  orientation  of  nanofibers  enhanced  the osteogenic differentiation of stem cells. The in vitro results showed that the aligned biocomposite nanofibrous scaffolds of PCL/nHA/PVA could be a potential substrate for tissue engineering applications, especially in the field of artificial bone implant.

  2. Smart scaffolds in bone tissue engineering: A systematicreview of literature

    Institute of Scientific and Technical Information of China (English)

    Saeed Reza Motamedian; Sepanta Hosseinpour; Mitra Ghazizadeh Ahsaie; Arash Khojasteh

    2015-01-01

    AIM To improve osteogenic differentiation and attachmentof cells.METHODS: An electronic search was conducted inPubMed from January 2004 to December 2013. Studieswhich performed smart modifications on conventionalbone scaffold materials were included. Scaffoldswith controlled release or encapsulation of bioactivemolecules were not included. Experiments which did notinvestigate response of cells toward the scaffold (cellattachment, proliferation or osteoblastic differentiation)were excluded.RESULTS: Among 1458 studies, 38 met the inclusion andexclusion criteria. The main scaffold varied extensivelyamong the included studies. Smart modificationsincluded addition of growth factors (group Ⅰ-11 studies),extracellular matrix-like molecules (group Ⅱ-13 studies)and nanoparticles (nano-HA) (group Ⅲ-17 studies). In allgroups, surface coating was the most commonly appliedapproach for smart modification of scaffolds. In group I,bone morphogenetic proteins were mainly used as growthfactor stabilized on polycaprolactone (PCL). In groupⅡ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequentscaffolds used. In the third group, nano-HA with PCL andchitosan were used the most. As variable methods wereused, a thorough and comprehensible compare betweenthe results and approaches was unattainable.CONCLUSION: Regarding the variability in methodologyof these in vitro studies it was demonstrated that smartmodification of scaffolds can improve tissue properties.

  3. Preparation of hybrid biomaterials for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Vilma Conceição Costa

    2007-03-01

    Full Text Available Tissue engineering has evolved from the use of biomaterials for bone substitution that fulfill the clinical demands of biocompatibility, biodegradability, non-immunogeneity, structural strength and porosity. Porous scaffolds have been developed in many forms and materials, but few reached the need of adequate physical, biological and mechanical properties. In the present paper we report the preparation of hybrid porous polyvinyl alcohol (PVA/bioactive glass through the sol-gel route, using partially and fully hydrolyzed polyvinyl alcohol, and perform structural characterization. Hybrids containing PVA and bioactive glass with composition 58SiO2-33CaO-9P2O5 were synthesized by foaming a mixture of polymer solution and bioactive glass sol-gel precursor solution. Sol-gel solution was prepared from mixing tetraethoxysilane (TEOS, triethylphosphate (TEP, and calcium chloride as chemical precursors. The hybrid composites obtained after aging and drying at low temperature were chemically and morphologically characterized through infrared spectroscopy and scanning electron microscopy. The degree of hydrolysis of PVA, concentration of PVA solution and different PVA-bioglass composition ratios affect the synthesis procedure. Synthesis parameters must be very well combined in order to allow foaming and gelation. The hybrid scaffolds obtained exhibited macroporous structure with pore size varying from 50 to 600 µm.

  4. Fabrication of polylactide nanocomposite scaffolds for bone tissue engineering applications

    Energy Technology Data Exchange (ETDEWEB)

    Mkhabela, Vuyiswa J.; Ray, Suprakas Sinha [Department of Applied Chemistry, University of Johannesburg, Doornfontein 2028 (South Africa); DST/CSIR National Centre for Nanostructured Materials, Council for Scientific and Industrial Research, Pretoria 0001 (South Africa)

    2015-05-22

    Highly porous three-dimensional polylactide (PLA) scaffolds were obtained from PLA incorporated with different amounts of chitosan-modified montmorillonite (CS-MMT), through solvent casting and particulate leaching method. The processed scaffolds were tested in vitro for their possible application in bone tissue engineering. Scaffolds were characterized by Focused Ion Beam Scanning Electron Microscopy (FIB SEM), Fourier Transform Infra-Red (FTIR), and X-Ray Diffraction (XRD) to study their structure and intermolecular interactions. Bioresorbability tests in simulated body fluid (pH 7.4) were conducted to assess the response of the scaffolds in a simulated physiological condition. The FIB SEM images of the scaffolds showed a porous architecture with gradual change in morphology with increasing CS-MMT concentration. FTIR analysis revealed the presence of both PLA and CS-MMT particles on the surface of the scaffolds. XRD showed that the crystalline unit cell type was the same for all the scaffolds, and crystallinity decreased with an increase in CS-MMT concentration. The scaffolds were found to be bioresorbable, with rapid bioresorbability on the scaffolds with a high CS-MMT concentration.

  5. Fabrication of polylactide nanocomposite scaffolds for bone tissue engineering applications

    Science.gov (United States)

    Mkhabela, Vuyiswa J.; Ray, Suprakas Sinha

    2015-05-01

    Highly porous three-dimensional polylactide (PLA) scaffolds were obtained from PLA incorporated with different amounts of chitosan-modified montmorillonite (CS-MMT), through solvent casting and particulate leaching method. The processed scaffolds were tested in vitro for their possible application in bone tissue engineering. Scaffolds were characterized by Focused Ion Beam Scanning Electron Microscopy (FIB SEM), Fourier Transform Infra-Red (FTIR), and X-Ray Diffraction (XRD) to study their structure and intermolecular interactions. Bioresorbability tests in simulated body fluid (pH 7.4) were conducted to assess the response of the scaffolds in a simulated physiological condition. The FIB SEM images of the scaffolds showed a porous architecture with gradual change in morphology with increasing CS-MMT concentration. FTIR analysis revealed the presence of both PLA and CS-MMT particles on the surface of the scaffolds. XRD showed that the crystalline unit cell type was the same for all the scaffolds, and crystallinity decreased with an increase in CS-MMT concentration. The scaffolds were found to be bioresorbable, with rapid bioresorbability on the scaffolds with a high CS-MMT concentration.

  6. In vitro osteoinductive potential of porous monetite for bone tissue engineering

    OpenAIRE

    2014-01-01

    Tissue engineering–based bone grafts are emerging as a viable alternative treatment modality to repair and regenerate tissues damaged as a result of disease or injury. The choice of the biomaterial component is a critical determinant of the success of the graft or scaffold; essentially, it must induce and allow native tissue integration, and most importantly mimic the hierarchical structure of the native bone. Calcium ...

  7. Soft Tissue Biomechanical Modeling for Computer Assisted Surgery

    CERN Document Server

    2012-01-01

      This volume focuses on the biomechanical modeling of biological tissues in the context of Computer Assisted Surgery (CAS). More specifically, deformable soft tissues are addressed since they are the subject of the most recent developments in this field. The pioneering works on this CAS topic date from the 1980's, with applications in orthopaedics and biomechanical models of bones. More recently, however, biomechanical models of soft tissues have been proposed since most of the human body is made of soft organs that can be deformed by the surgical gesture. Such models are much more complicated to handle since the tissues can be subject to large deformations (non-linear geometrical framework) as well as complex stress/strain relationships (non-linear mechanical framework). Part 1 of the volume presents biomechanical models that have been developed in a CAS context and used during surgery. This is particularly new since most of the soft tissues models already proposed concern Computer Assisted Planning, with ...

  8. The Digital Astronaut Project Bone Remodeling Model

    Science.gov (United States)

    Pennline, James A.; Mulugeta, Lealem; Lewandowski, Beth E.; Thompson, William K.; Sibonga, Jean D.

    2014-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur: (1) The most commonly used countermeasure against bone loss has been prescribed exercise, (2) However, current exercise countermeasures do not completely eliminate bone loss in long duration, 4 to 6 months, spaceflight, (3,4) leaving the astronaut susceptible to early onset osteoporosis and a greater risk of fracture later in their lives. The introduction of the Advanced Resistive Exercise Device, coupled with improved nutrition, has further minimized the 4 to 6 month bone loss. But further work is needed to implement optimal exercise prescriptions, and (5) In this light, NASA's Digital Astronaut Project (DAP) is working with NASA physiologists to implement well-validated computational models that can help understand the mechanisms of bone demineralization in microgravity, and enhance exercise countermeasure development.

  9. Impact of dental implant insertion method on the peri-implant bone tissue: Experimental study

    Directory of Open Access Journals (Sweden)

    Stamatović Novak

    2013-01-01

    Full Text Available Background/Aim. The function of dental implants depends on their stability in bone tissue over extended period of time, i.e. on osseointegration. The process through which osseointegration is achieved depends on several factors, surgical insertion method being one of them. The aim of this study was to histopathologically compare the impact of the surgical method of implant insertion on the peri-implant bone tissue. Methods. The experiment was performed on 9 dogs. Eight weeks following the extraction of lower premolars implants were inserted using the one-stage method on the right mandibular side and two-stage method on the left side. Three months after implantation the animals were sacrificed. Three distinct regions of bone tissue were histopathologically analyzed, the results were scored and compared. Results. In the specimens of one-stage implants increased amount of collagen fibers was found in 5 specimens where tissue necrosis was also observed. Only moderate osteoblastic activity was found in 3 sections. The analysis of bone-to-implant contact region revealed statistically significantly better results regarding the amount of collagen tissue fibers for the implants inserted in the two-stage method (Wa = 59 105, α = 0.05. No necrosis and osteoblastic activity were observed. Conclusion. Better results were achieved by the two-stage method in bone-to-implant contact region regarding the amount of collagen tissue, while the results were identical regarding the osteoblastic activity and bone tissue necrosis. There was no difference between the methods in the bone-implant interface region. In the bone tissue adjacent to the implant the results were identical regarding the amount of collagen tissue, osteoblastic reaction and bone tissue necrosis, while better results were achieved by the two-stage method regarding the number of osteocytes.

  10. From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges.

    Science.gov (United States)

    Baroli, Biancamaria

    2009-04-01

    Tissue engineering is an emerging multidisciplinary field of investigation focused on the regeneration of diseased or injured tissues through the delivery of appropriate molecular and mechanical signals. Therefore, bone tissue engineering covers all the attempts to reestablish a normal physiology or to speed up healing of bone in all musculoskeletal disorders and injuries that are lashing modern societies. This article attempts to give a pharmaceutical perspective on the production of engineered man-made bone grafts that are described as implantable tissue engineering therapeutics, and to highlight the importance of understanding bone composition and structure, as well as osteogenesis and bone healing processes, to improve the design and development of such implants. In addition, special emphasis is given to pharmaceutical aspects that are frequently minimized, but that, instead, may be useful for formulation developments and in vitro/in vivo correlations.

  11. Unusual endosteally formed bone tissue in a patagonian basal sauropodomorph dinosaur.

    Science.gov (United States)

    Cerda, Ignacio A; Chinsamy, Anusuya; Pol, Diego

    2014-08-01

    Mussaurus patagonicus (Dinosauria: Sauropodomorpha) is a basal sauropodomorph from the Late Triassic of southern Argentina that is known from a large number of individuals, including juveniles, subadults, and adults. Here, we report on the occurrence of an unusual bone tissue in an individual of M. patagonicus. The rather atypical bone tissue is located within the femoral medullary cavity and also occurs within several erosion cavities of the midinner part of the cortex. This tissue is well vascularized and is composed of a matrix that consists of abundant and densely packed osteocyte lacunae. Although some features of this tissue resembles avian medullary bone, the histological features are distinctive and share more features with the pathological, reactive bone produced in extant birds in response to a retrovirus-induced disease (avian osteopetrosis). Here, we also discuss and provide histological features to effectively differentiate endosteally formed medullary bone from pathological avian osteopetrosis.

  12. Multilayer Nanoscale Encapsulation of Biofunctional Peptides to Enhance Bone Tissue Regeneration In Vivo.

    Science.gov (United States)

    Gentile, Piergiorgio; Ferreira, Ana Marina; Callaghan, Jill T; Miller, Cheryl A; Atkinson, Joss; Freeman, Christine; Hatton, Paul V

    2017-02-07

    Bone tissue healing is a dynamic process that is initiated by the recruitment of osteoprogenitor cells followed by their migration, proliferation, differentiation, and development of a mineralizing extracellular matrix. The work aims to manufacture a functionalized porous membrane that stimulates early events in bone healing for initiating a regenerative cascade. Layer-by-layer (LbL) assembly is proposed to modify the surface of osteoconductive electrospun meshes, based on poly(lactic-co-glycolic acid) and nanohydroxyapatite, by using poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) as polyelectrolytes. Molecular cues are incorporated by grafting peptide fragments into the discrete nanolayers. KRSR (lysine-arginine-serine-arginine) sequence is grafted to enhance cell adhesion and proliferation, NSPVNSKIPKACCVPTELSAI to guide bone marrow mesenchymal stem cells differentiation in osteoblasts, and FHRRIKA (phenylalanine-histidine-arginine-arginine-isoleucine-lysine-alanine) to improve mineralization matrix formation. Scanning electron microscopy, infrared spectroscopy, and X-ray photoelectron spectroscopy demonstrate the successful surface functionalization. Furthermore, the peptide incorporation enhances cellular processes, with good viability and significant increase of alkaline phosphatase activity, osteopontin, and osteocalcin. The functionalized membrane induces a favorable in vivo response after implantation for four weeks in nonhealing rat calvarial defect model. It is concluded that the multilayer nanoencapsulation of biofunctional peptides using LbL approach has significant potential as innovative manufacturing technique to improve bone regeneration in orthopedic and craniofacial medical devices.

  13. Fabrication and characterization of electrospun osteon mimicking scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Andric, T. [Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Sampson, A.C. [Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Freeman, J.W., E-mail: jwfreeman@vt.edu [Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States)

    2011-01-01

    Skeletal loss and bone deficiencies are a major worldwide problem with over 600,000 procedures performed in the US alone annually, making bone one of the most transplanted tissues, second to blood only. Bone is a composite tissue composed of organic matrix, inorganic bone mineral, and water. Structurally bone is organized into two distinct types: trabecular (or cancellous) and cortical (or compact) bones. Trabecular bone is characterized by an extensive interconnected network of pores. Cortical bone is composed of tightly packed units, called osteons, oriented parallel along to the axis of the bone. While the majority of scaffolds attempt to replicate the structure of the trabecular bone, fewer attempts have been made to create scaffolds to mimic the structure of cortical bone. The aim of this study was to develop a technique to fabricate scaffolds that mimic the organization of an osteon, the structural unit of cortical bone. We successfully built a rotating stage for PGA fibers and utilized it for collecting electrospun nanofibers and creating scaffolds. Resulting scaffolds consisted of concentric layers of electrospun PLLA or gelatin/PLLA nanofibers wrapped around PGA microfiber core with diameters that ranged from 200 to 600 {mu}m. Scaffolds were mineralized by incubation in 10x simulated body fluid, and scaffolds composed of 10%gelatin/PLLA had significantly higher amounts of calcium phosphate. The electrospun scaffolds also supported cellular attachment and proliferation of MC3T3 cells over the period of 28 days.

  14. Biomimetic composite scaffolds containing bioceramics and collagen/gelatin for bone tissue engineering - A mini review.

    Science.gov (United States)

    Kuttappan, Shruthy; Mathew, Dennis; Nair, Manitha B

    2016-12-01

    Bone is a natural composite material consisting of an organic phase (collagen) and a mineral phase (calcium phosphate, especially hydroxyapatite). The strength of bone is attributed to the apatite, while the collagen fibrils are responsible for the toughness and visco-elasticity. The challenge in bone tissue engineering is to develop such biomimetic composite scaffolds, having a balance between biological and biomechanical properties. This review summarizes the current state of the field by outlining composite scaffolds made of gelatin/collagen in combination with bioactive ceramics for bone tissue engineering application.

  15. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues

    OpenAIRE

    Zhang, Gong; Yuan, Hai; Chen, Xianshuai; Wang, Weijun; Chen, Jianyu; Liang, Jimin; Zhang, Peng

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque...

  16. Effects of gas produced by degradation of Mg–Zn–Zr Alloy on cancellous bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jingbo; Jiang, Hongfeng [Tianjin Hospital, 300211 Tianjin (China); Bi, Yanze; Sun, Jin e; Chen, Minfang; Liu, Debao [School of Materials Science and Engineering, Tianjin University of Technology, 300384 Tianjin (China)

    2015-10-01

    Mg–Zn–Zr alloy cylinders were implanted into the femoral condyles of Japanese big-ear white rabbits. X-ray showed that by 12 weeks following implantation the implant became obscure, around which the low-density area appeared and enlarged. By 24 weeks, the implant was more obscure and the density of the surrounding cancellous bone increased. Scanning electron microscopy examination showed bone tissue on the surface of the alloy attached by living fibers at 12 weeks. Micro-CT confirmed that new bone tissue on the surface of the residual alloy implant increased from 12 weeks to 24 weeks. By 12 weeks, many cavities in the cancellous bone tissue around the implant were noted with a CT value, similar to gas value, and increasing by 24 weeks (P < 0.01). Histological examination of hard tissue slices showed that bone tissue was visibly attached to the alloy in the femoral condyle at 12 weeks. The trabecular bone tissues became more intact and dense, and the cavities were filled with soft tissue at 24 weeks. In general, gas produced by the degradation of the Mg–Zn–Zr alloy can cause cavitation within cancellous bone, which does not affect osteogenesis of Mg alloy. - Highlights: • The degradation of Mg alloy in cancellous bone causes cavitation around the alloy. • At first, the CT value of the cavities is similar to the gas value. • The area of the cavities enlarges gradually by 12 weeks. • The cavities are filled with bone tissue and soft tissue gradually.

  17. Recent progresses in gene delivery-based bone tissue engineering.

    Science.gov (United States)

    Lu, Chia-Hsin; Chang, Yu-Han; Lin, Shih-Yeh; Li, Kuei-Chang; Hu, Yu-Chen

    2013-12-01

    Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches.

  18. Ultrasonic tissue characterization for monitoring nanostructured TiO{sub 2}-induced bone growth

    Energy Technology Data Exchange (ETDEWEB)

    Rus, G [Department of Structural Mechanics, University of Granada, Politecnico de Fuentenueva, 18071 Granada (Spain); Garcia-MartInez, J [Department of Inorganic Chemistry, University of Alicante, E-03690 Alicante (Spain)

    2007-07-21

    The use of bioactive nanostructured TiO{sub 2} has recently been proposed for improving orthopaedic implant adhesion due to its improved biocompatibility with bone, since it induces: (i) osteoblast function, (ii) apatite nucleation and (iii) protein adsorption. The present work focuses on a non-ionizing radiation emitting technique for quantifying in real time the improvement in terms of mechanical properties of the surrounding bone due to the presence of the nanostructured TiO{sub 2} prepared by controlled precipitation and acid ageing. The mechanical strength is the ultimate goal of a bone implant and is directly related to the elastic moduli. Ultrasonics are high frequency mechanical waves and are therefore suited for characterizing elastic moduli. As opposed to echographic techniques, which are not correlated to elastic properties and are not able to penetrate bone, a low frequency ultrasonic transmission test is proposed, in which a P-wave is transmitted through the specimen and recorded. The problem is posed as an inverse problem, in which the unknown is a set of parameters that describe the mechanical constants of the sequence of layers. A finite element numerical model that depends on these parameters is used to predict the transformation of the waveform and compare to the measurement. The parameters that best describe the real tissue are obtained by minimizing the discrepancy between the real and numerically predicted waveforms. A sensitivity study to the uncertainties of the model is performed for establishing the feasibility of using this technique to investigate the macroscopic effect on bone growth of nanostructured TiO{sub 2} and its beneficial effect on implant adhesion.

  19. Instrumental and laboratory assessment of stressful remodelling processes in bone tissue at total hip replacement

    Directory of Open Access Journals (Sweden)

    E.V. Karjakina

    2010-06-01

    Full Text Available Research objective is to estimate stressful remodelling features of bone tissue according to the densitometry data and to the level of biochemical markers of bone resorption and formation in total hip replacement (THR. Bone tissue mineral density (BTMD, condition of calcium-phosphoric metabolism and biochemical markers of bone formation (osteocalcin and bone isoenzyme of alkaline phosphatase and resorption (С-terminal bodypeptide of the I type collagen have been determined in 52 patients with coxarthrosis of ll-lll stages with marked joint dysfunction before and after THR. The control group included 24 donors. The data were considered to be reliable when the probability index was р<0,05. The reliable (р<0,05 change of BTMD was determined only in 3-6 months after the operation, whereas the change of biochemical markers of remodeling had already been done after 1,5-3 months, allowing to define the group of patients with obvious negative bone balance: strong predominance of resorption processes without compensation of the subsequent adequate osteogenesis, that subsequently could lead to significant bone tissue deficiency in the area adjacent to the endoprosthesis. Changes of indices of calcium-phosphoric metabolism were not certain during the investigation term. ln conclusion it is to state that biochemical markers of remodeling in comparison with BTMD allow to estimate objectively features of adaptive bone tissue remodeling after THR in earlier periods and to define group of patients with sharp intensification of metabolism and obvious negative bone balance

  20. A TETRACYCLINE LABELING STUDY OF SUBCHONDRAL BONE TISSUES IN OSTEOARTHRITIC HIP JOINT

    Institute of Scientific and Technical Information of China (English)

    徐荣辉; 柴本甫

    1992-01-01

    Seven female patients (mean age of 56 years) with advanced hip joint osteoarthritis underwent total hip replacement. Four days before operation they were given oral tetracycline for two days. During operation specimens were taken from the white articular cartilage, the yellowish articular cartilage and the ivory bone together with their subchondral bone tissues. The undecalcified specimens were cut into 10 μm sections and observed under the fluorescence microscope. In all the specimens the following findings could be observed. 1. The osteoarthritic articular cartilage became thinner, with uneven surface and fissures. 2. The superficial and deep surfaces and the central part of the subchondral bone plate showed bright golden yellow fluorescence. It reflected extensive new bone formation. 3. The subchondral bone trabeculae also revealed bright golden yellow fluorescence on their peripheral borders, so trabeculae turned thicker obviously. 4. The marrow tissues between the bone trabeculae exhibited particulate or spherical bright golden yellow fluorescence, reflecting new bone formation in the marrow. The particulate and spherical bright golden yellow fluorescent materials might aggregate, enlarge and merge into large piece of new bone and they also fused with the neighbouring bone trabeculae. The aforementioned changes in the structure of the subchondral bone tissues increased greatly the mass in the osteoarthritic femoral head.

  1. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    Energy Technology Data Exchange (ETDEWEB)

    Campi, G.; Pezzotti, G. [Institute of Crystallography, CNR, via Salaria Km 29.300, I-00015, Monterotondo Roma (Italy); Fratini, M. [Centro Fermi -Museo Storico della Fisica e Centro Studi e Ricerche ' Enrico Fermi' , Roma (Italy); Ricci, A. [Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, D-22607 Hamburg (Germany); Burghammer, M. [European Synchrotron Radiation Facility, B. P. 220, F-38043 Grenoble Cedex (France); Cancedda, R.; Mastrogiacomo, M. [Istituto Nazionale per la Ricerca sul Cancro, and Dipartimento di Medicina Sperimentale dell' Università di Genova and AUO San Martino Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132, Genova (Italy); Bukreeva, I.; Cedola, A. [Institute for Chemical and Physical Process, CNR, c/o Physics Dep. at Sapienza University, P-le A. Moro 5, 00185, Roma (Italy)

    2013-12-16

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  2. Histological Features and Biocompatibility of Bone and Soft Tissue Substitutes in the Atrophic Alveolar Ridge Reconstruction

    Directory of Open Access Journals (Sweden)

    Carlo Maiorana

    2016-01-01

    Full Text Available The reconstruction of the atrophic alveolar ridges for implant placement is today a common procedure in dentistry daily practice. The surgical reconstruction provides for the optimization of the supporting bone for the implants and a restoration of the amount of keratinized gingiva for esthetic and functional reasons. In the past, tissue regeneration has been performed with autogenous bone and free gingival or connective tissue grafts. Nowadays, bone substitutes and specific collagen matrix allow for a complete restoration of the atrophic ridge without invasive harvesting procedures. A maxillary reconstruction of an atrophic ridge by means of tissue substitutes and its histological features are then presented.

  3. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

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    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  4. Effect of intervening tissues on ultrasonic backscatter measurements of bone: An in vitro study.

    Science.gov (United States)

    Hoffmeister, Brent K; Spinolo, P Luke; Sellers, Mark E; Marshall, Peyton L; Viano, Ann M; Lee, Sang-Rok

    2015-10-01

    Ultrasonic backscatter techniques are being developed to diagnose osteoporosis. Tissues that lie between the transducer and the ultrasonically interrogated region of bone may produce errors in backscatter measurements. The goal of this study is to investigate the effects of intervening tissues on ultrasonic backscatter measurements of bone. Measurements were performed on 24 cube shaped specimens of human cancellous bone using a 5 MHz transducer. Measurements were repeated after adding a 1 mm thick plate of cortical bone to simulate the bone cortex and a 3 cm thick phantom to simulate soft tissue at the hip. Signals were analyzed to determine three apparent backscatter parameters (apparent integrated backscatter, frequency slope of apparent backscatter, and frequency intercept of apparent backscatter) and three backscatter difference parameters [normalized mean backscatter difference (nMBD), normalized slope of the backscatter difference, and normalized intercept of the backscatter difference]. The apparent backscatter parameters were impacted significantly by the presence of intervening tissues. In contrast, the backscatter difference parameters were not affected by intervening tissues. However, only one backscatter difference parameter, nMBD, demonstrated a strong correlation with bone mineral density. Thus, among the six parameters tested, nMBD may be the best choice for in vivo backscatter measurements of bone when intervening tissues are present.

  5. Enhanced bone tissue regeneration using a 3D printed microstructure incorporated with a hybrid nano hydrogel.

    Science.gov (United States)

    Heo, Dong Nyoung; Castro, Nathan J; Lee, Se-Jun; Noh, Hanaul; Zhu, Wei; Zhang, Lijie Grace

    2017-04-20

    Three-dimensional (3D) functional constructs with biomimetic mechanical and chemical properties are ideal for various regenerative medicine applications. These properties of 3D fabricated constructs mainly depend on the intrinsic characteristics of the materials and fabrication method. In this respect, the current use of hydrogels for musculoskeletal tissue repair is not ideal due to the lack of suitable mechanical properties, as well as the high biomimetic requirement for success. To overcome this limitation, we developed a novel functionalized hydrogel with bioactive gold nanoparticles (GNPs), reinforcing a 3D printed microstructure via fused deposition modeling (FDM) for bone tissue regeneration. We used biodegradable thermoplastic polylactic acid (PLA) as the 3D printed microstructure in combination with photo-curable gelatin hydrogels as the encapsulation matrix for the incorporation of cyclic RGD conjugated GNPs (RGNP), and investigated their mechanical properties. In addition, human adipose-derived stem cells (ADSCs) were encapsulated within the gelatin hydrogel and examined for viability, morphology, and osteogenic differentiation in vitro. The results showed that the stiffness of the composite hydrogel on reinforcing a 3D printed microstructure can be readily modulated to simulate the stiffness of the human mandibular condyle. ADSCs encapsulated in the composite structures remained viable within the hydrogel and showed excellent spreading on the 3D printed PLA microstructure. More importantly, osteogenic differentiation with incorporated RGNPs promoted significantly higher gene expression of osteogenic specific factors. Therefore, reinforced composite hydrogels are suitable for stem cell differentiation control and bone tissue regeneration.

  6. Effect of Chemistry on Osteogenesis and Angiogenesis Towards Bone Tissue Engineering Using 3D Printed Scaffolds.

    Science.gov (United States)

    Bose, Susmita; Tarafder, Solaiman; Bandyopadhyay, Amit

    2017-01-01

    The functionality or survival of tissue engineering constructs depends on the adequate vascularization through oxygen transport and metabolic waste removal at the core. This study reports the presence of magnesium and silicon in direct three dimensional printed (3DP) tricalcium phosphate (TCP) scaffolds promotes in vivo osteogenesis and angiogenesis when tested in rat distal femoral defect model. Scaffolds with three different interconnected macro pore sizes were fabricated using direct three dimensional printing. In vitro ion release in phosphate buffer for 30 days showed sustained Mg(2+) and Si(4+) release from these scaffolds. Histolomorphology and histomorphometric analysis from the histology tissue sections revealed a significantly higher bone formation, between 14 and 20% for 4-16 weeks, and blood vessel formation, between 3 and 6% for 4-12 weeks, due to the presence of magnesium and silicon in TCP scaffolds compared to bare TCP scaffolds. The presence of magnesium in these 3DP TCP scaffolds also caused delayed TRAP activity. These results show that magnesium and silicon incorporated 3DP TCP scaffolds with multiscale porosity have huge potential for bone tissue repair and regeneration.

  7. The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls.

    Science.gov (United States)

    L Newton, Anna; J Hanks, Lynae; Davis, Michelle; Casazza, Krista

    2013-01-01

    Investigation of the physiologic relevance of bone marrow adipose tissue (BMAT) during growth may promote understanding of the bone-fat axis and confluence with metabolic factors. The objective of this pilot investigation was two-fold: (1) to evaluate the relationships among total body fat, bone mineral content (BMC) and femoral BMAT during childhood and underlying metabolic determinants and (2) to determine if the relationships differ by race. Participants included white and non-Hispanic black girls (n=59) ages 4-10 years. Femoral BMAT volume was measured by magnetic resonance imaging, BMC and body fat by dual-energy X-ray absorptiometry. Metabolic parameters were assessed in the fasted state. Total fat and BMC were positively associated with BMAT; however, simultaneous inclusion of BMC and body fat in the statistical model attenuated the association between BMC and BMAT. Differences in BMAT volume were observed, non-Hispanic black girls exhibiting marginally greater BMAT at age eight (P=0.05) and white girls exhibiting greater BMAT at age ten (PBMAT and leptin (P=0.02) and adiponectin (P=0.002) in white girls while BMAT and insulin were inversely related in non-Hispanic black girls (P=0.008). Our findings revealed a positive relationship between BMAT, body fat and BMC, although body fat, respective to leptin, contributed partly to the relationship between BMAT and BMC. Despite large differences in total fat between non-Hispanic black and white, the relationship between BMAT and BMC was similar to white girls. However, this relationship appeared to be impacted through different mechanisms according to race.

  8. Effects of gas produced by degradation of Mg-Zn-Zr Alloy on cancellous bone tissue.

    Science.gov (United States)

    Wang, Jingbo; Jiang, Hongfeng; Bi, Yanze; Sun, Jin e; Chen, Minfang; Liu, Debao

    2015-10-01

    Mg-Zn-Zr alloy cylinders were implanted into the femoral condyles of Japanese big-ear white rabbits. X-ray showed that by 12 weeks following implantation the implant became obscure, around which the low-density area appeared and enlarged. By 24 weeks, the implant was more obscure and the density of the surrounding cancellous bone increased. Scanning electron microscopy examination showed bone tissue on the surface of the alloy attached by living fibers at 12 weeks. Micro-CT confirmed that new bone tissue on the surface of the residual alloy implant increased from 12 weeks to 24 weeks. By 12 weeks, many cavities in the cancellous bone tissue around the implant were noted with a CT value, similar to gas value, and increasing by 24 weeks (PZr alloy can cause cavitation within cancellous bone, which does not affect osteogenesis of Mg alloy. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Bone And Soft Tissue Changes In Patients With Spinal Cord Injury And Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dionyssiotis Yannis

    2014-12-01

    Full Text Available In patients with spinal cord injury and multiple sclerosis, deterioration of body composition (changes in bone, fat and muscle mass is associated with increased risk for diseases such as coronary artery heart disease, non-insulin dependent diabetes mellitus, lipid metabolism abnormalities, and osteoporotic fractures in these patients. Immobility leads to a changing pattern of loading in the paralyzed areas, and secondary alteration in structure. However, bone and soft tissue changes in these patients are usually neglected. The purpose of this article is to update on the pathophysiological mechanisms leading to bone and soft tissue changes, and to increase the awareness of the treating physicians with respect to bone, muscle and fat loss and their consequences aiming to obtain measures to prevent bone and soft tissue loss in these patients.

  10. Osteoimmunology: the study of the relationship between the immune system and bone tissue.

    Science.gov (United States)

    Arboleya, Luis; Castañeda, Santos

    2013-01-01

    Bone tissue is a highly regulated structure, which plays an essential role in various physiological functions. Through autocrine and paracrine mechanisms, bone tissue is involved in hematopoiesis, influencing the fate of hematopoietic stem cells. There are a number of molecules shared by bone cells and immune system cells indicating that there are multiple connections between the immune system and bone tissue. In order to pool all the knowledge concerning both systems, a new discipline known under the term «osteoimmunology» has been developed. Their progress in recent years has been exponential and allowed us to connect and increase our knowledge in areas not seemingly related such as rheumatoid erosion, postmenopausal osteoporosis, bone metastases or periodontal disease. In this review, we have tried to summarize the most important advances that have occurred in the last decade, especially in those areas of interest related to rheumatology. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  11. Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering

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    Aldo R. Boccaccini

    2010-07-01

    Full Text Available Traditionally, bioactive glasses have been used to fill and restore bone defects. More recently, this category of biomaterials has become an emerging research field for bone tissue engineering applications. Here, we review and discuss current knowledge on porous bone tissue engineering scaffolds on the basis of melt-derived bioactive silicate glass compositions and relevant composite structures. Starting with an excerpt on the history of bioactive glasses, as well as on fundamental requirements for bone tissue engineering scaffolds, a detailed overview on recent developments of bioactive glass and glass-ceramic scaffolds will be given, including a summary of common fabrication methods and a discussion on the microstructural-mechanical properties of scaffolds in relation to human bone (structure-property and structure-function relationship. In addition, ion release effects of bioactive glasses concerning osteogenic and angiogenic responses are addressed. Finally, areas of future research are highlighted in this review.

  12. Magnesium substitution in brushite cements for enhanced bone tissue regeneration.

    Science.gov (United States)

    Cabrejos-Azama, Jatsue; Alkhraisat, Mohammad Hamdan; Rueda, Carmen; Torres, Jesús; Blanco, Luis; López-Cabarcos, Enrique

    2014-10-01

    We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p<0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations.

  13. Regeneration of damaged osteoporotic bone tissue with synthetic biomaterials

    Directory of Open Access Journals (Sweden)

    Petrović Nenad D.

    2014-01-01

    Full Text Available In some cases in oral and maxillofacial surgery, bone regeneration is required in large quantities. One of these cases is osteoporosis. This paper aims to show the new approach to solving this problem of impaired healing of bone defects in the jaw, as well as in other bones, with the use of synthetic biomaterials whose properties resemble the natural bone. Latest development in this area present an effort to create local drug-delivery systems for BMPs and growth factors, direct delivery of MSCs, as well as scaffolds for osteoconduction and also to utilize nanotechnology to synthesize composite biomaterials, predominantly based on HAp and polymers, that would mimic the natural bone nanocomposite architecture. There is also a tendency to create injectable biomaterials for simplified application.

  14. Quercetin inhibits inflammatory bone resorption in a mouse periodontitis model.

    Science.gov (United States)

    Napimoga, Marcelo H; Clemente-Napimoga, Juliana T; Macedo, Cristina G; Freitas, Fabiana F; Stipp, Rafael N; Pinho-Ribeiro, Felipe A; Casagrande, Rubia; Verri, Waldiceu A

    2013-12-27

    Periodontitis is a disease that leads to bone destruction and represents the main cause of tooth loss in adults. The development of aggressive periodontitis has been associated with increased inflammatory response that is induced by the presence of a subgingival biofilm containing Aggregatibacter actinomycetemcomitans. The flavonoid quercetin (1) is widespread in vegetables and fruits and exhibits many biological properties for possible medical and clinical applications such as its anti-inflamatory and antioxidant effects. Thus, in the present study, the properties of 1 have been evaluated in bone loss and inflammation using a mouse periodontitis model induced by A. actinomycetemcomitans infection. Subcutaneous treatment with 1 reduced A. actinomycetemcomitans-induced bone loss and IL-1β, TNF-α, IL-17, RANKL, and ICAM-1 production in the gingival tissue without affecting bacterial counts. These results demonstrated that quercetin exhibits protective effects in A. actinomycetemcomitans-induced periodontitis in mice by modulating cytokine and ICAM-1 production.

  15. Bone marrow–derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice

    Science.gov (United States)

    Koh, Young Jun; Kang, Shinae; Lee, Hyuek Jong; Choi, Tae-Saeng; Lee, Ho Sub; Cho, Chung-Hyun; Koh, Gou Young

    2007-01-01

    Little is known about whether bone marrow–derived circulating progenitor cells (BMDCPCs) can transdifferentiate into adipocytes in adipose tissues or play a role in expanding adipocyte number during adipose tissue growth. Using a mouse bone marrow transplantation model, we addressed whether BMDCPCs can transdifferentiate into adipocytes under standard conditions as well as in the settings of diet-induced obesity, rosiglitazone treatment, and exposure to G-CSF. We also addressed the possibility of transdifferentiation to adipocytes in a murine parabiosis model. In each of these settings, our findings indicated that BMDCPCs did not transdifferentiate into either unilocular or multilocular adipocytes in adipose tissues. Most BMDCPCs became resident and phagocytic macrophages in adipose tissues — which resembled transdifferentiated multilocular adipocytes by appearance, but displayed cell surface markers characteristic for macrophages — in the absence of adipocyte marker expression. When exposed to adipogenic medium in vitro, bone marrow cells differentiated into multilocular, but not unilocular, adipocytes, but transdifferentiation was not observed in vivo, even in the contexts of adipose tissue regrowth or dermal wound healing. Our results suggest that BMDCPCs do not transdifferentiate into adipocytes in vivo and play little, if any, role in expanding the number of adipocytes during the growth of adipose tissues. PMID:18060029

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

    Science.gov (United States)

    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.

  17. Modeling and experimentation of bone drilling forces.

    Science.gov (United States)

    Lee, JuEun; Gozen, B Arda; Ozdoganlar, O Burak

    2012-04-05

    Prediction and control of bone drilling forces are critical to the success of many orthopaedic operations. Uncontrolled and large forces can cause drill-bit breakage, drill breakthrough, excessive heat generation, and mechanical damage to the bone. This paper presents a mechanistic model for prediction of thrust forces and torques experienced during bone drilling. The model incorporates the radially varying drill-bit geometry and cutting conditions analytically, while capturing the material and friction properties empirically through a specific energy formulation. The forces from the chisel edge are modeled by considering the indentation process that occurs in the vicinity of the drill-bit axis. A procedure is outlined to calibrate the specific energies, where only a small number of calibration experiments are required for a wide range of drilling conditions and drill-bit geometry. The calibration parameters for the cortical portions of bovine tibia are identified through drilling tests. Subsequently, a series of validation tests are conducted under different feed rates and spindle speeds. The thrust forces and torques were observed to vary considerably between bones from different animals. The forces from the model were seen to match well with those from the experimentation within the inherent variations from the bone characteristics. The model can be used to select favorable drilling conditions, to assist in robotic surgeries, and to design optimal orthopaedic drill bits. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Human dental pulp stem cell is a promising autologous seed cell for bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    LI Jing-hui; LIU Da-yong; ZHANG Fang-ming; WANG Fan; ZHANG Wen-kui; ZHANG Zhen-ting

    2011-01-01

    Background The seed cell is a core problem in bone tissue engineering research.Recent research indicates that human dental pulp stem cells (hDPSCs) can differentiate into osteoblasts in vitro,which suggests that they may become a new kind of seed cells for bone tissue engineering.The aim of this study was to evaluate the osteogenic differentiation of hDPSCs in vitro and bone-like tissue formation when transplanted with three-dimensional gelatin scaffolds in vivo,and hDPSCs may become appropriate seed cells for bone tissue engineering.Methods We have utilized enzymatic digestion to obtain hDPSCs from dental pulp tissue extracted during orthodontic treatment.After culturing and expansion to three passages,the cells were seeded in 6-well plates or on three-dimensional gelatin scaffolds and cultured in osteogenic medium.After 14 days in culture,the three-dimensional gelatin scaffolds were implanted subcutaneously in nude mice for 4 weeks.In 6-well plate culture,osteogenesis was assessed by alkaline phosphatase staining,Von Kossa staining,and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the osteogenesis-specific genes type I collagen (COL l),bone sialoprotein (BSP),osteocalcin (OCN),RUNX2,and osterix (OSX).In three-dimensional gelatin scaffold culture,X-rays,hematoxylin/eosin staining,and immunohistochemical staining were used to examine bone formation.Results In vitro studies revealed that hDPSCs do possess osteogenic differentiation potential.In vivo studies revealed that hDPSCs seeded on gelatin scaffolds can form bone structures in heterotopic sites of nude mice.Conclusions These findings suggested that hDPSCs may be valuable as seed cells for bone tissue engineering.As a special stem cell source,hDPSCs may blaze a new path for bone tissue engineering.

  19. Self-assembled composite matrix in a hierarchical 3-D scaffold for bone tissue engineering

    DEFF Research Database (Denmark)

    Chen, Muwan; Le, Dang Quang Svend; Baatrup, Anette

    2011-01-01

    It is of high clinical relevance in bone tissue engineering that scaffolds promote a high seeding efficiency of cells capable of osteogenic differentiation, such as human bone marrow-derived mesenchymal stem cells (hMSCs). We evaluated the effects of a novel polycaprolactone (PCL) scaffold on h...

  20. Lamellar bone is an incremental tissue reconciling enamel rhythms, body size, and organismal life history.

    Science.gov (United States)

    Bromage, Timothy G; Lacruz, Rodrigo S; Hogg, Russell; Goldman, Haviva M; McFarlin, Shannon C; Warshaw, Johanna; Dirks, Wendy; Perez-Ochoa, Alejandro; Smolyar, Igor; Enlow, Donald H; Boyde, Alan

    2009-05-01

    Mammalian enamel formation is periodic, including fluctuations attributable to the daily biological clock as well as longer-period oscillations that enigmatically correlate with body mass. Because the scaling of bone mass to body mass is an axiom of vertebrate hard tissue biology, we consider that long-period enamel formation rhythms may reflect corresponding and heretofore unrecognized rhythms in bone growth. The principal aim of this study is to seek a rhythm in bone growth demonstrably related to enamel oscillatory development. Our analytical approach is based in morphology, using a variety of hard tissue microscopy techniques. We first ascertain the relationship among long-period enamel rhythms, the striae of Retzius, and body mass using a large sample of mammalian taxa. In addition, we test whether osteocyte lacuna density (a surrogate for rates of cell proliferation) in bone is correlated with mammalian body mass. Finally, using fluorescently labeled developing bone tissues, we investigate whether the bone lamella, a fundamental microanatomical unit of bone, relates to rhythmic enamel growth increments. Our results confirm a positive correlation between long-period enamel rhythms and body mass and a negative correlation between osteocyte density and body mass. We also confirm that lamellar bone is an incremental tissue, one lamella formed in the species-specific time dependency of striae of Retzius formation. We conclude by contextualizing our morphological research with a current understanding of autonomic regulatory control of the skeleton and body mass, suggesting a central contribution to the coordination of organismal life history and body mass.

  1. Mandibular Bone and Soft Tissues Necrosis Caused by an Arsenical Endodontic Preparation Treated with Piezoelectric Device

    Directory of Open Access Journals (Sweden)

    A. Giudice

    2013-01-01

    Full Text Available This paper describes a case of wide mandibular bone necrosis associated with significant soft tissues injury after using an arsenical endodontic preparation in the right lower second molar for endodontic purpose. Authors debate about the hazardous effects of the arsenic paste and the usefulness of piezosurgery for treatment of this drug related bone necrosis.

  2. Assessment of bone formation capacity using in vivo transplantation assays: procedure and tissue analysis

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ditzel, Nicholas; Kassem, Moustapha

    2008-01-01

    ) in immunodeficient mice is the standard method for in vivo assessment of bone formation capacity of a particular cell type. The method is easy to perform and provides reproducible results. Assessment of the donor origin of tissue formation is possible, especially in the case of human-to-mouse transplanta tion...... transplantation methods in testing bone formationpotential of human mesenchymal stem cells....

  3. A Systematic Review on Complications of Tissue Preservation Surgical Techniques in Percutaneous Bone Conduction Hearing Devices

    NARCIS (Netherlands)

    Verheij, Emmy; Bezdjian, Aren; Grolman, Wilko; Thomeer, Hans

    OBJECTIVE:: To investigate skin-related postoperative complications from tissue preservation approaches in percutaneous bone conduction device (BCD) implantations. DATA SOURCES:: PubMed, Embase, and Cochrane Library. STUDY SELECTION:: We identified studies on BCDs including the opted surgical

  4. Microhardness of Bone Tissue After Different Alloy Implantation

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    Nataliia Zaitseva

    2015-09-01

    Full Text Available Integral indicator of bone quality is microhardness, which depends both on the condition of the inorganic component and the quality of the extracellular organic matrix. There are a lot of researches indicated microhardness changes around the metal implants, but it is not clear how it change distant from injured place. The aim of our research was to determine the microhardness of the femoral bone at different terms after the implantation of metal alloys with different composition. 65 rabbits were random in 5 groups – intact, control (bone defect and 3 experimental. We used TiVT6 alloy with high elasticity module and β- (Ti-Zr alloy with low Young module for the experimental groups. All alloys were implanted in distal epiphysis of femur. Bone microhardness was detected in periimplanted zone as well as in middle of diaphysis and proximal epiphysis. Injury of bone leads to a decrease in the hardness in the zone of the defec as well as in distal zones, followed by recovery up to 6 month. Use the classic high-modulus alloy TiVT6 leads to a significant decrease in the microhardness of all sections of bone in the early and late postoperative period. Implantation of low modulus alloy β (Ti-Zr leads to a reduction of hardness just after 1 and 3 months after the injury, and the use of hydroxyapatite coating significantly reduces the loss of bone quality at all times after implantation.

  5. Bone tissue response to plasma-nitrided titanium implant surfaces

    Directory of Open Access Journals (Sweden)

    Emanuela Prado FERRAZ

    2015-02-01

    Full Text Available A current goal of dental implant research is the development of titanium (Ti surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration. Objective The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments. Material and Methods Surface treatments consisted of 20% N2 and 80% H2, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses. Results Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area. Conclusion Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces.

  6. Bone tissue response to plasma-nitrided titanium implant surfaces.

    Science.gov (United States)

    Ferraz, Emanuela Prado; Sverzut, Alexander Tadeu; Freitas, Gileade Pereira; Sá, Juliana Carvalho; Alves, Clodomiro; Beloti, Marcio Mateus; Rosa, Adalberto Luiz

    2015-01-01

    A current goal of dental implant research is the development of titanium (Ti) surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration. Objective The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments. Material and Methods Surface treatments consisted of 20% N2 and 80% H2, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses. Results Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area. Conclusion Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces.

  7. Magnesium substitution in brushite cements for enhanced bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cabrejos-Azama, Jatsue, E-mail: jacaza@farm.ucm.es [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); Alkhraisat, Mohammad Hamdan; Rueda, Carmen [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Torres, Jesús [Facultad de Ciencias de la salud URJC, Alcorcón, Madrid (Spain); Blanco, Luis [Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); López-Cabarcos, Enrique [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain)

    2014-10-01

    We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p < 0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations. - Highlights: • The Mg-CPCs promote higher new bone formation than the CPC. • The incorporation of magnesium ions in CPC improves osteoblasts proliferation. • Mg-CPC is a bone substitute with controllable biodegradable properties. • We suggest that the use of Mg ions could improve the clinical efficiency of CPCs.

  8. Fusion of intestinal epithelial cells with bone marrow derived cells is dispensable for tissue homeostasis.

    Science.gov (United States)

    de Jong, Joan H; Rodermond, Hans M; Zimberlin, Cheryl D; Lascano, Valeria; De Sousa E Melo, Felipe; Richel, Dick J; Medema, Jan Paul; Vermeulen, Louis

    2012-01-01

    The epithelial lining of the intestine is characterized by an immense cellular turn-over ascertaining an extensive regenerative capacity. Multiple reports suggest that besides the local intestinal stem cell pool, circulating cells of bone marrow origin (BMDCs) contribute to this process by fusing with the epithelial lineage. However, the functional relevance of these observations is unknown. In the present study we employ a model system in which we cannot only detect cell fusion but also examine the functional importance of this process in vivo. Our results indicate that fusion between BMDCs and intestinal epithelial cells is an extremely rare event under physiological conditions. More importantly, by employing a system in which fusion-derived cells can be specifically deleted after extensive tissue damage, we present evidence that cell fusion is not relevant for tissue regeneration. Our data decisively demonstrates that intestinal epithelial homeostasis and regeneration is not dependent on cell fusion involving BMDCs.

  9. Bioceramic-collagen scaffolds loaded with human adipose-tissue derived stem cells for bone tissue engineering.

    Science.gov (United States)

    Daei-Farshbaf, Neda; Ardeshirylajimi, Abdolreza; Seyedjafari, Ehsan; Piryaei, Abbas; Fadaei Fathabady, Fatemeh; Hedayati, Mehdi; Salehi, Mohammad; Soleimani, Masoud; Nazarian, Hamid; Moradi, Sadegh-Lotfalah; Norouzian, Mohsen

    2014-02-01

    The combination of bioceramics and stem cells has attracted the interest of research community for bone tissue engineering applications. In the present study, a combination of Bio-Oss(®) and type 1 collagen gel as scaffold were loaded with human adipose-tissue derived mesenchymal stem cells (AT-MSCs) after isolation and characterization, and the capacity of them for bone regeneration was investigated in rat critical size defects using digital mammography, multi-slice spiral computed tomography imaging and histological analysis. 8 weeks after implantation, no mortality or sign of inflammation was observed in the site of defect. According to the results of imaging analysis, a higher level of bone regeneration was observed in the rats receiving Bio-Oss(®)-Gel compared to untreated group. In addition, MSC-seeded Bio-Oss-Gel induced the highest bone reconstruction among all groups. Histological staining confirmed these findings and impressive osseointegration was observed in MSC-seeded Bio-Oss-Gel compared with Bio-Oss-Gel. On the whole, it was demonstrated that combination of AT-MSCs, Bio-Oss and Gel synergistically enhanced bone regeneration and reconstruction and also could serve as an appropriate structure to bone regenerative medicine and tissue engineering application.

  10. Transgenic Mouse Model for Reducing Oxidative Damage in Bone

    Science.gov (United States)

    Schreurs, A.-S.; Torres, S.; Truong, T.; Kumar, A.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

    2014-01-01

    Exposure to musculoskeletal disuse and radiation result in bone loss; we hypothesized that these catabolic treatments cause excess reactive oxygen species (ROS), and thereby alter the tight balance between bone resorption by osteoclasts and bone formation by osteoblasts, culminating in bone loss. To test this, we used transgenic mice which over-express the human gene for catalase, targeted to mitochondria (MCAT). Catalase is an anti-oxidant that converts the ROS hydrogen peroxide into water and oxygen. MCAT mice were shown previously to display reduced mitochondrial oxidative stress and radiosensitivity of the CNS compared to wild type controls (WT). As expected, MCAT mice expressed the transgene in skeletal tissue, and in marrow-derived osteoblasts and osteoclast precursors cultured ex vivo, and also showed greater catalase activity compared to wildtype (WT) mice (3-6 fold). Colony expansion in marrow cells cultured under osteoblastogenic conditions was 2-fold greater in the MCAT mice compared to WT mice, while the extent of mineralization was unaffected. MCAT mice had slightly longer tibiae than WT mice (2%, P less than 0.01), although cortical bone area was slightly lower in MCAT mice than WT mice (10%, p=0.09). To challenge the skeletal system, mice were treated by exposure to combined disuse (2 wk Hindlimb Unloading) and total body irradiation Cs(137) (2 Gy, 0.8 Gy/min), then bone parameters were analyzed by 2-factor ANOVA to detect possible interaction effects. Treatment caused a 2-fold increase (p=0.015) in malondialdehyde levels of bone tissue (ELISA) in WT mice, but had no effect in MCAT mice. These findings indicate that the transgene conferred protection from oxidative damage caused by treatment. Unexpected differences between WT and MCAT mice emerged in skeletal responses to treatment.. In WT mice, treatment did not alter osteoblastogenesis, cortical bone area, moment of inertia, or bone perimeter, whereas in MCAT mice, treatment increased these

  11. The ectopic study of tissue-engineered bone with hBMP-4 gene modified bone marrow stromal cells in rabbits

    Institute of Scientific and Technical Information of China (English)

    JIANG Xin-quan; CHEN Jian-guo; Sébastien Gittens; CHEN Chuan-jun; ZHANG Xiu-li; ZHANG Zhi-yuan

    2005-01-01

    Background Tissue-engineering techniques combined with gene therapy have been recently reported to improve osteogenesis. In this study, tissue-engineered bone constructed by human Bone Morphogenetic Protein 4 (hBMP-4) gene-modified bone marrow stromal cells (bMSCs) was explored in an ectopic bone formation model in rabbits.Methods A pEGFP-hBMP-4 mammalian plasmid (EGFP: Enhanced Green Fluorescent Protein) was constructed by subcloning techniques. bMSCs obtained from rabbits were cultured and transfected with either pEGFP-hBMP-4, pEGFP or left uninfected in vitro. Transfer efficiency was detected through the expression of EGFP. Transcription of the target gene was detected by RT-PCR. Alkaline phosphatase (ALP) and Von Kossa tests were also conducted to explore the phenotypes of osteoblasts. The autologous bMSCs of the 3 groups were then combined with Natural Non-organic Bone (NNB), a porous hydroxyapatite implant with a dimension of 6 mm×6 mm×3 mm, at a concentration of 5×107 cells/ml. They were subsequently implanted into 6 rabbits subcutaneously using NNB alone as a blank control (6 implants per group). Four weeks after surgery, the implants were evaluated with histological staining and computerized analysis of new bone formation.Results pEGFP-hBMP-4 expression plasmid was constructed. Under optimal conditions, gene transfer efficiency reached more than 30%. Target gene transfer could strengthen the transcription of BMP-4, and increase the expression of ALP as well as the number of calcium nodules. In the ectopic animal model, NNB alone could not induce new bone formation. The new bone area formed in the bMSCs group was (17.2±7.1)%, and pEGFP group was (14.7±6.1)%, while pEGFP-hBMP-4 group was (29.5±8.2)%, which was the highest among the groups (F=7.295, P<0.01). Conclusions The mammalian hBMP-4 expression plasmid was successfully constructed and a comparatively high transfer efficiency was achieved. The gene transfer technique enhanced the expression of BMP

  12. The regulation of bone turnover in ameloblastoma using an organotypic in vitro co-culture model

    Science.gov (United States)

    Eriksson, Tuula M; Day, Richard M; Fedele, Stefano; Salih, Vehid M

    2016-01-01

    Ameloblastoma is a rare, odontogenic neoplasm with benign histopathology, but extensive, local infiltrative capacity through the bone tissue it originates in. While the mechanisms of ameloblastoma invasion through the bone and bone absorption are largely unknown, recent investigations have indicated a role of the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand regulatory mechanisms. Here, we present results obtained using a novel in vitro organotypic tumour model, which we have developed using tissue engineering techniques. Using this model, we analysed the expression of genes involved in bone turnover and detected a 700-fold increase in receptor activator of nuclear factor kappa-B ligand levels in the co-culture models with ameloblastoma cells cultured with bone cells. The model described here can be used for gene expression studies, as a basis for drug testing or for a more tailored platform for testing of the behaviour of different ameloblastoma tumours in vitro.

  13. Impact of dental implant insertion method on the peri-implant bone tissue: Experimental study

    OpenAIRE

    Stamatović Novak; Matić Smiljana; Tatić Zoran; Petković-Ćurčin Aleksandra; Vojvodić Danilo; Rakić Mia

    2013-01-01

    Background/Aim. The function of dental implants depends on their stability in bone tissue over extended period of time, i.e. on osseointegration. The process through which osseointegration is achieved depends on several factors, surgical insertion method being one of them. The aim of this study was to histopathologically compare the impact of the surgical method of implant insertion on the peri-implant bone tissue. Methods. The experiment was performed on 9 dogs. Eight weeks following t...

  14. Bone Regeneration Based on Tissue Engineering Conceptions-A 21st Century Perspective

    Institute of Scientific and Technical Information of China (English)

    Jan Henkel; Maria A. Woodruff; Devakara R. Epari; Roland Steck; Vaida Glatt; Ian C. Dickinson; Peter FM Choong; Michael A. Schuetz; Dietmar W. Hutmacher

    2013-01-01

    The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteo-conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer-ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental“origin”require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.

  15. In-vitro analysis of the effect of gentamicin and polyhexanide on bone tissue.

    Science.gov (United States)

    Kock, Hans-Jürgen; Ernst, Dirk; Jethon, Frank; Fabry, Werner

    2013-04-01

    Though anti-infectives have been used for a long time in surgical procedures, the effect on bone tissue has not been determined for most antibiotics and antiseptics. In our in vitro study, 4x4x8 mm(3) blocks of rabbit cancellous bone tissue were incubated with Ringer's solution, gentamicin and Lavasorb(®) each for time intervals of 15 minutes, 30 minutes, one hour, four hours and eight hours. Samples were examined double blinded through optical and electron microscopy. Tissue degeneration was observed in all samples. It was low in Ringer's solution. Samples with Lavasorb showed a moderate degeneration after 15 and 30 minutes, which was accelerated after one hour. Gentamicin led to a moderate degeneration of bone tissue after 15 and 30 minutes and to a more accelerated degeneration after one hour. The effect of gentamicin on bone tissue was more pronounced than the effect of Lavasorb. This investigation showed that local application of Lavasorb or gentamicin on bone tissue should be restricted to 30 minutes, while Lavasorb showed a better tissue tolerability. This finding could have clinical implications for the management of wounds with open osseous tissue and should be further investigated by in vivo studies.

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

    Science.gov (United States)

    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.

  17. Nanocomposite scaffolds with tunable mechanical and degradation capabilities: co-delivery of bioactive agents for bone tissue engineering.

    Science.gov (United States)

    Cattalini, Juan P; Roether, Judith; Hoppe, Alexander; Pishbin, Fatemeh; Haro Durand, Luis; Gorustovich, Alejandro; Boccaccini, Aldo R; Lucangioli, Silvia; Mouriño, Viviana

    2016-10-21

    Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.

  18. Low intensity pulsed ultrasound increases the mechanical properties of the healing tissues at bone-tendon junction.

    Science.gov (United States)

    Lu, Min-Hua; Zheng, Yong-Ping; Huang, Qing-Hua; Lu, Hong-Bin; Qin, Ling

    2009-01-01

    The re-establishment of bone-tendon junction (BTJ) tissues is involved in many trauma and reconstructive surgeries. A direct BTJ repair requires a long period of immobilization which may be associated with a postoperative weak knee. In this study, we investigated if low-intensity pulsed ultrasound treatment increases the material properties of healing tissues at bone-tendon junction (BTJ) after partial patellectomy using rabbit models. Standard partial patellectomy was conducted on one knee of twenty four rabbits which were randomly divided into an ultrasound group and a control group. The bony changes of BTJ complexes around the BTJ healing interface were measured by anteroposterior x-ray radiographs; then the volumetric bone-mineral density (BMD) of the new bone was assessed using a peripheral computed tomography scanner (pQCT). The stiffness of patellar cartilage, fibrocartilage at the healing interface and the tendon were measured in situ using a novel noncontact ultrasound water jet indentation system. Not only significantly more newly formed bone at the BTJ healing interface but also increased stiffness of the junction tissues were found in the ultrasound group compared with the controls at week 18. In addition, the ultrasound group also showed significantly 44% higher BMD at week 6 than controls.

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

    Science.gov (United States)

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

    2017-03-07

    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.

  20. Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice

    DEFF Research Database (Denmark)

    Erikstrup, Lise Tornvig; Mosekilde, Leif; Justesen, J;

    2001-01-01

    proliferator activated receptor-gamma (PPARgamma). Histomorphometric analysis of proximal tibia was performed in order to quantitate the amount of trabecular bone volume per total volume (BV/TV %), adipose tissue volume per total volume (AV/TV %), and hematopoietic marrow volume per total volume (HV...

  1. Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium.

    Science.gov (United States)

    Wang, Ping; Liu, Xian; Zhao, Liang; Weir, Michael D; Sun, Jirun; Chen, Wenchuan; Man, Yi; Xu, Hockin H K

    2015-05-01

    Human induced pluripotent stem cells (hiPSCs) are an exciting cell source with great potential for tissue engineering. Human bone marrow mesenchymal stem cells (hBMSCs) have been used in clinics but are limited by several disadvantages, hence alternative sources of MSCs such as umbilical cord MSCs (hUCMSCs) are being investigated. However, there has been no report comparing hiPSCs, hUCMSCs and hBMSCs for bone regeneration. The objectives of this pilot study were to investigate hiPSCs, hUCMSCs and hBMSCs for bone tissue engineering, and compare their bone regeneration via seeding on biofunctionalized macroporous calcium phosphate cement (CPC) in rat cranial defects. For all three types of cells, approximately 90% of the cells remained alive on CPC scaffolds. Osteogenic genes were up-regulated, and mineral synthesis by cells increased with time in vitro for all three types of cells. The new bone area fractions at 12weeks (mean±sd; n=6) were (30.4±5.8)%, (27.4±9.7)% and (22.6±4.7)% in hiPSC-MSC-CPC, hUCMSC-CPC and hBMSC-CPC respectively, compared to (11.0±6.3)% for control (pcells (p>0.1). New blood vessel density was higher in cell-seeded groups than control (pcells was confirmed via immunohistochemical staining. In conclusion, (1) hiPSCs, hUCMSCs and hBMSCs greatly enhanced bone regeneration, more than doubling the new bone amount of cell-free CPC control; (2) hiPSC-MSCs and hUCMSCs represented viable alternatives to hBMSCs; (3) biofunctionalized macroporous CPC-stem cell constructs had a robust capacity for bone regeneration. Published by Elsevier Ltd.

  2. Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

    Science.gov (United States)

    Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni

    2014-01-01

    Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.

  3. Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model

    Science.gov (United States)

    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

  4. [Reaction of bone tissue elements on synthetic bioresorbable materials based on lactic and glycolic acids].

    Science.gov (United States)

    Kulakov, A A; Grigor'ian, A S

    2014-01-01

    The aim of the study was to evaluate the adverse effects of synthetic polymeric bioresorbable materials based on lactic and glycolic acids on the bone tissue. The study was carried-out on 40 Wister-line rats. Four types of bioresorbable polymeric materials were implanted: PolyLactide Glycolide Acid (PLGA), Poly-L-Lactide Acid (PLLA); Poly-96L/4D-Lactide Acid (96/4 PLDLA); Poly-70L/30D-Lactide Acid (70/30 PLDLA). The results showed connective tissue formation (fibrointegration) bordering bone adjacent to implanted materials. This proved the materials to cause pathogenic influence on the bone which mechanisms are described in the article.

  5. Guided tissue regeneration using a collagen barrier and bone swaging technique in noncontained infrabony defects.

    Science.gov (United States)

    Kodama, Toshiro; Minabe, Masato; Sugiyama, Takashi; Mitarai, Eiko; Fushimi, Hajime; Kitsugi, Daisuke; Tsutsumi, Kouji; Katsuki, Makiko

    2013-01-01

    This clinical study evaluated the effectiveness of guided tissue regeneration using a resorbable collagen membrane and bone swaging in noncontained infrabony defects by assessing changes in probing pocket depth, probing attachment level, and radiographic bone level after 6 months, 1 year, and 2 years. Postsurgical clinical and radiographic measurements were statistically significantly different from presurgical measurements. The rate of bone fill was positively associated with the baseline depth of the bone defect but not associated with the width. The noncontained infrabony defects treated with this combined regenerative method improved clinically and radiographically.

  6. Biodegradable hybrid tissue engineering scaffolds for reconstruction of large bone defects

    Science.gov (United States)

    Barati, Danial

    Complex skeletal injuries and large bone fractures are still a significant clinical problem in US. Approximately 1.5 million Americans (veterans, their families, and civilians) every year suffer from bone loss due to traumatic skeletal injuries, infection, and resection of primary tumors that require extensive grafting to bridge the gap. The US bone graft market is over $2.2 billion a year. Due to insufficient mechanical stability, lack of vascularity, and inadequate resorption of the graft, patients with traumatic large skeletal injuries undergo multiple costly operations followed by extensive recovery steps to maintain proper bone alignment and length. Current strategies for repairing damaged or diseased bones include autologous or allograft bone transplantations. However, limited availability of autografts and risk of disease transmission associated with allografts have necessitated the search for the development of new bone graft options and strategies. The overall goal of this project is to develop a much-needed bone-mimetic engineered graft as a substitute for current strategies providing required bone grafts for reconstruction of large bone defects. This project will use the structure of natural cortical bone as a guide to produce an engineered bone graft with balanced strength, osteogenesis, vascularization, and resorption. The outcome of this project will be a biodegradable hybrid scaffold system (similar to natural cortical bone) including a mechanically strong scaffold allowing for mechanical stability of the load-bearing defect site and a soft and highly porous structure such as a hydrogel phase which will allow for efficient cell and growth factor delivery into the defect implantation site, cell niche establishment and promotion of mineralization. Successful completion of this project will transform bone graft technology for regeneration of complex bone defects from a frozen or freeze-dried allograft to a safe, infection-free, mechanically

  7. The effect of osteoporosis treatments on fatigue properties of cortical bone tissue

    Directory of Open Access Journals (Sweden)

    Garry R. Brock

    2015-06-01

    Full Text Available Bisphosphonates are commonly prescribed for treatment of osteoporosis. Long-term use of bisphosphonates has been correlated to atypical femoral fractures (AFFs. AFFs arise from fatigue damage to bone tissue that cannot be repaired due to pharmacologic treatments. Despite fatigue being the primary damage mechanism of AFFs, the effects of osteoporosis treatments on fatigue properties of cortical bone are unknown. To examine if fatigue-life differences occur in bone tissue after different pharmacologic treatments for osteoporosis, we tested bone tissue from the femurs of sheep given a metabolic acidosis diet to induce osteoporosis, followed by treatment with a selective estrogen reception modulator (raloxifene, a bisphosphonate (alendronate or zoledronate, or parathyroid hormone (teriparatide, PTH. Beams of cortical bone tissue were created and tested in four-point bending fatigue to failure. Tissue treated with alendronate had reduced fatigue life and less modulus loss at failure compared with other treatments, while tissue treated with PTH had a prolonged fatigue life. No loss of fatigue life occurred with zoledronate treatment despite its greater binding affinity and potency compared with alendronate. Tissue mineralization measured by microCT did not explain the differences seen in fatigue behavior. Increased fatigue life with PTH suggests that current treatment methods for AFF could have beneficial effects for restoring fatigue life. These results indicate that fatigue life differs with each type of osteoporosis treatment.

  8. A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Qin; Ya-Nan Wang

    2012-01-01

    A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper.The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model.Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model),but also predict the realtime development pattern of BMC and BFE,as well as the dynamics of osteoblasts (OBA),osteoclasts (OCA),nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme,which can hardly be monitored through experiment.In conclusion,the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass.More importantly,this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated.The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies.Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

  9. Gene Expression Changes in Femoral Head Necrosis of Human Bone Tissue

    Directory of Open Access Journals (Sweden)

    Bernadett Balla

    2011-01-01

    Full Text Available Osteonecrosis of the femoral head (ONFH is the result of an interruption of the local circulation and the injury of vascular supply of bone. Multiple factors have been implicated in the development of the disease. However the mechanism of ischemia and necrosis in non-traumatic ONFH is not clear. The aim of our investigation was to identify genes that are differently expressed in ONFH vs. non-ONFH human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from ONFH male patients and 8 bone tissue samples from non-ONFH men were examined. The expression differences of selected 117 genes were analyzed by TaqMan probe-based quantitative real-time RT-PCR system. The significance test indicated marked differences in the expression of nine genes between ONFH and non-ONFH individuals. These altered genes code for collagen molecules, an extracellular matrix digesting metalloproteinase, a transcription factor, an adhesion molecule, and a growth factor. Canonical variates analysis demonstrated that ONFH and non-ONFH bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via canonical TGFB pathway as well as genes coding for extracellular matrix composing collagen type molecules. The markedly altered gene expression profile observed in the ONFH of human bone tissue may provide further insight into the pathogenetic process of osteonecrotic degeneration of bone.

  10. Bone tissue density modification in treatment of shin pseudoarthrosis by transosseous compressive osteosynthesis

    Directory of Open Access Journals (Sweden)

    Tishkov N.V.

    2011-12-01

    Full Text Available Objective is to detect bone mineral density along the shin according to «Esperanto» levels by Hounsfield's scale. Materials and methods. The analysis of density modification in 25 patients with pseudoarthrosis of tibia with predominant localization in a lower one-third of bone has been carried out. Results. By means of computed tomography it has been revealed that the bone tissue density of the tibia in the process of false joint union when using the compressive variant of combined transosseous osteosynthesis has changed according to the regularity reproducing phase character of the accumulation of mineral substances in the bone. Conclution. The growth of mineral density of the bone tissue during treatment spreads in the directions from proximal and distal metaepiphyses to the zone of pseudoarthrosis knitting

  11. A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue.

    Science.gov (United States)

    Takatori, T; Tomii, S; Terazawa, K; Nagao, M; Kanamori, M; Tomaru, Y

    1991-01-01

    The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860-0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples.

  12. An ectopic study of tissue-engineered bone with Nell-1 gene modified rat bone marrow stromal cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    HU Jing-zhou; ZHANG Zhi-yuan; ZHAO Jun; ZHANG Xiu-li; LIU Gen-tao; JIANG Xin-quan

    2009-01-01

    Background Tissue engineering techniques combined with gene therapy have been recently used to improve osteogenesis. NEL-like molecule-1 (Nell-1), a novel growth factor, has been reported to have specificity for osteochondral lineage. The study assessed the osteogenic differentiation of rat bone marrow stromal cells (bMSCs) after Nell-1 gene modification and examined its ectopic bone formation ability in a nude mice model with tissue engineering technique.Methods bMSCs obtained from Fischer 344 rats were transduced with either AdNell-1 (Nell-1 group) or Ad-β-galactosidase (AdLacZ, LacZ group) or left untransduced (untransduced group). The expression of Nell-1 protein was determined by Western blotting and transfer efficiency was assessed, mRNA expressions of osteopontin (OP), bone sialoprotein (BSP) and osteocalcin (OC) were assessed by real-time PCR 0, 3, 7, 14, and 21 days after gene transfer. Alkaline phosphatase (ALP) activity was measured and von Kossa test was also conducted. Finally, with a tissue engineering technique, gene transduced bMSCs, combining with β-tricalcium phosphate (β-TCP) at a concentration of 2×107 cells/ml, were implanted at subcutaneous sites on the back of nude mice. Four weeks after surgery, the implants were evaluated with histological staining and computerized analysis of new bone formation.Results Under current transduction conditions, gene transfer efficiency reached (57.9±6.8)%. Nell-1 protein was detected in Nell-1 group but not in untransduced group and LacZ group. Induced by Nell-1, BSPand OPexpression were increased at intermediate stage and OC expression was increased at later stage. ALP activity and the number of calcium nodules were highest in Nell-1 group. Four weeks after implanted into nude mice subcutaneously, the percentage of new bone area in Nell-1 group was (18.1±5.0)%, significantly higher than those of untransduced group (11.3±3.2)% and LacZ group (12.3±3.1)% (P<0.05).Conclusions This study has demonstrated

  13. (*) Central Growth Factor Loaded Depots in Bone Tissue Engineering Scaffolds for Enhanced Cell Attraction.

    Science.gov (United States)

    Quade, Mandy; Knaack, Sven; Akkineni, Ashwini Rahul; Gabrielyan, Anastasia; Lode, Anja; Rösen-Wolff, Angela; Gelinsky, Michael

    2017-08-01

    Tissue engineering, the application of stem and progenitor cells in combination with an engineered extracellular matrix, is a promising strategy for bone regeneration. However, its success is limited by the lack of vascularization after implantation. The concept of in situ tissue engineering envisages the recruitment of cells necessary for tissue regeneration from the host environment foregoing ex vivo cell seeding of the scaffold. In this study, we developed a novel scaffold system for enhanced cell attraction, which is based on biomimetic mineralized collagen scaffolds equipped with a central biopolymer depot loaded with chemotactic agents. In humid milieu, as after implantation, the signaling factors are expected to slowly diffuse out of the central depot forming a gradient that stimulates directed cell migration toward the scaffold center. Heparin, hyaluronic acid, and alginate have been shown to be capable of depot formation. By using vascular endothelial growth factor (VEGF) as model factor, it was demonstrated that the release kinetics can be adjusted by varying the depot composition. While alginate and hyaluronic acid are able to reduce the initial burst and prolong the release of VEGF, the addition of heparin led to a much stronger retention that resulted in an almost linear release over 28 days. The biological activity of released VEGF was proven for all variants using an endothelial cell proliferation assay. Furthermore, migration experiments with endothelial cells revealed a relationship between the degree of VEGF retention and migration distance: cells invaded deepest in scaffolds containing a heparin-based depot indicating that the formation of a steep gradient is crucial for cell attraction. In conclusion, this novel in situ tissue engineering approach, specifically designed to recruit and accommodate endogenous cells upon implantation, appeared highly promising to stimulate cell invasion, which in turn would promote vascularization and finally new

  14. Feasibility of endoscopic laser speckle imaging modality in the evaluation of auditory disorder: study in bone-tissue phantom

    Science.gov (United States)

    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.

  15. Bone tissue stiffness in the mandibular condyle is dependent on the direction and density of the cancellous structure.

    NARCIS (Netherlands)

    Eijden, T.M. van; Ruijven, L.J. van; Giesen, E.B.W.

    2004-01-01

    Variation in the apparent stiffness of cancellous bone is generally ascribed to variation in cancellous structure and density, while the bone tissue stiffness is assumed to be constant. The purpose of the present study was to examine whether the bone tissue stiffness is dependent on the direction an

  16. Determination of the relationship between collagen cross-links and the bone-tissue stiffness in the porcine mandibular condyle

    NARCIS (Netherlands)

    Willems, N.M.B.K.; Mulder, L.; Bank, R.A.; Grünheid, T.; Toonder, J.M.J. den; Zentner, A.; Langenbach, G.E.J.

    2011-01-01

    Although bone-tissue stiffness is closely related to the degree to which bone has been mineralized, other determinants are yet to be identified. We, therefore, examined the extent to which the mineralization degree, collagen, and its cross-links are related to bone-tissue stiffness. A total of 50 ca

  17. A histological investigation on tissue responses to titanium implants in cortical bone of the rat femur.

    Science.gov (United States)

    Ohtsu, A; Kusakari, H; Maeda, T; Takano, Y

    1997-03-01

    Implant materials are placed under various sites-including cortical bone, spongy bone, and bone marrow-at the same time according to the depth at implantation. Although cortical bone is an important site for the prognosis of implantation, detailed reports on tissue responses to implantation have been meager. The present study aims to reveal tissue responses to pure titanium implantation in rat femoris cortical bone. The rats received titanium bars surgically in their femurs and were sacrificed 1 day to 40 weeks post-implantation. The prepared tissue specimens were processed for light and transmission electron microscopy (TEM). Further histochemical detections were performed. One day post-implantation, empty osteocytic lacunae indicating degeneration of osteocytes were found in pre-existing cortical bone around the implant. Such pre-existing bone was replaced by new bone, but remained in part even 40 weeks post-implantation. Light microscopy showed that direct contact between the implant and new bone was identified 12 weeks post-implantation. Chronological and ultrastructural observation showed that new bone deposition appeared to proceed toward the implant, and that the intervening layer at the interface was derived from the degenerated debris of multinucleated giant cells and/or osteoblasts. Furthermore, it seemed that the width of intervening layer varied in relation to the distance from the blood vessels. The cells showing tartrate resistant acid phosphatase activity possessed cytological features of osteoclasts under TEM; they were frequently observed in perivascular sites near the implants even after osseointegration, suggesting that bone remodeling took place steadily around the implant.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ehler, E; Sterling, D; Higgins, P [University of Minnesota, Minneapolis, MN (United States)

    2015-06-15

    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 several 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.

  19. Constitutive Laws and Failure Models for Compact Bones Subjected to Dynamic Loading

    CERN Document Server

    Pithioux, M; Jean, M

    2002-01-01

    Many biological tissues, such as bones and ligaments, are fibrous. The geometrical structure of these tissues shows that they exhibit a similar hierarchy in their ultra-structure and macro-structure. The aim of this work is to develop a model to study the failure of fibrous structures subjected to dynamic loading. The important feature of this model is that it describes failure in terms of the loss of cohesion between fibres. We have developed a model based on the lamellar structure of compact bone with fibres oriented at 0 degrees, 45 degrees and 90 degrees to the longitudinal axis of the bone, and have studied the influence of the model parameters on the failure process. Bone porosity and joint stress force at failure were found to be the most significant parameters. Using least square resolution, we deduced a phenomenological model of the lamellar structure. Finally, experimental results were found to be comparable with our numerical model.

  20. Modelling the temperature evolution of bone under high intensity focused ultrasound.

    Science.gov (United States)

    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

    2016-02-21

    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

  1. Modelling the temperature evolution of bone under high intensity focused ultrasound

    Science.gov (United States)

    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

  2. Non-viral gene therapy for bone tissue engineering.

    Science.gov (United States)

    Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

    2013-01-01

    The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

  3. Advanced computational workflow for the multi-scale modeling of the bone metabolic processes.

    Science.gov (United States)

    Dao, Tien Tuan

    2017-06-01

    Multi-scale modeling of the musculoskeletal system plays an essential role in the deep understanding of complex mechanisms underlying the biological phenomena and processes such as bone metabolic processes. Current multi-scale models suffer from the isolation of sub-models at each anatomical scale. The objective of this present work was to develop a new fully integrated computational workflow for simulating bone metabolic processes at multi-scale levels. Organ-level model employs multi-body dynamics to estimate body boundary and loading conditions from body kinematics. Tissue-level model uses finite element method to estimate the tissue deformation and mechanical loading under body loading conditions. Finally, cell-level model includes bone remodeling mechanism through an agent-based simulation under tissue loading. A case study on the bone remodeling process located on the human jaw was performed and presented. The developed multi-scale model of the human jaw was validated using the literature-based data at each anatomical level. Simulation outcomes fall within the literature-based ranges of values for estimated muscle force, tissue loading and cell dynamics during bone remodeling process. This study opens perspectives for accurately simulating bone metabolic processes using a fully integrated computational workflow leading to a better understanding of the musculoskeletal system function from multiple length scales as well as to provide new informative data for clinical decision support and industrial applications.

  4. [Bone tissue engineering. Reconstruction of critical sized segmental bone defects in the ovine tibia].

    Science.gov (United States)

    Reichert, J C; Epari, D R; Wullschleger, M E; Berner, A; Saifzadeh, S; Nöth, U; Dickinson, I C; Schuetz, M A; Hutmacher, D W

    2012-04-01

    Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds.Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

  5. Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

    NARCIS (Netherlands)

    A. Grefhorst (Aldo); J.C. van den Beukel (Anneke); A.F. van Houten (A.); J. Steenbergen (Jacobie); J.A. Visser (Jenny); A.P.N. Themmen (Axel)

    2015-01-01

    textabstractBackground: In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed

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

    Science.gov (United States)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    1999-01-01

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

  8. EFFECT OF OXIDATIVE STRESS ON HISTOARCHITECTONICS AND ELEMENTAL COMPOSITION OF BONE TISSUE OF THE VERTEBRAL BODY RATS

    Directory of Open Access Journals (Sweden)

    S. N. Lukanina

    2015-01-01

    vertebra while modeling the oxidative stress and increasing the content of Ca, P, Cu, Fe, Zn in bone tissue in compare to data of intact animals.Conclusion. Polyfunctional S-containing antioxidant of new generation “Tiophan” is a prospective remedy of protecting cells and matrix of bone tissue against infraction caused by active oxygen metabolites during an oxidative stress. 

  9. Bone tissue phantoms for optical flowmeters at large interoptode spacing generated by 3D-stereolithography.

    Science.gov (United States)

    Binzoni, Tiziano; Torricelli, Alessandro; Giust, Remo; Sanguinetti, Bruno; Bernhard, Paul; Spinelli, Lorenzo

    2014-08-01

    A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption coefficient, reduced scattering coefficient and refractive index of the optical phantom have been measured to ensure that the optical parameters reasonably reproduce real human bone tissue in vivo. An experimental demonstration of a possible use of the optical phantom, utilizing a laser-Doppler flowmeter, is also presented.

  10. Giant cell tumor of bone and tenosynovial tissue : surgical outcome

    NARCIS (Netherlands)

    Heijden, Lizz van der

    2014-01-01

    Giant cell tumor of bone (GCTB) is an intermediate, locally aggressive but rarely metastasizing tumor. Radiologically, GCTB shows typical lytic lesions. MR imaging is required to evaluate extent of GCTB for surgical planning. Preferred treatment for GCTB is extended curettage with local adjuvants, w

  11. Changes in functional activity of bone tissue cells under space flight conditions.

    Science.gov (United States)

    Rodionova, Natalia; Nesterenko, Olga; Kabitskaya, Olga

    osteoclasts. Among them are typical osteoclasts with 3 to 4 nuclei on a section, as well as the "giant" cells with 5 to 6 nuclei and a highly developed zone 2, in which organelles and structures are concentrated, providing for specific functions (primary and secondary lysosomes, heterophagous vacuoles, fibrous layer and "brush border"). The availability of these functionally active osteoclasts testify to the intensification of resorptive processes in remodelling zones. To confirm the obtained electronmicroscopic findings, the experiments were conducted on albino rats under model microgravity conditions ("tail suspension" method) with the use of radionuclides. The experiments with 3H-glycine demonstrated a lower isotope uptake in the osteogenetic cells compared with the control. The autoradiographic studies employing 3H-thymidine, showed that hind limbs unloading leads to a significant acceleration of osteoclast formation in zones of spongy bone reconstruction. Considering the obtained results, the cell mechanisms of osteoclast - osteoblast remodelling and bone tissue loss under the action of space flight factors are discussed.

  12. Bilateral maxillary sinus floor augmentation with tissue-engineered autologous osteoblasts and demineralized freeze-dried bone

    Directory of Open Access Journals (Sweden)

    Aashish Deshmukh

    2015-01-01

    Full Text Available The pneumatization of the maxillary sinus often results in a lack of sufficient alveolar bone for implant placement. In the last decades, maxillary sinus lift has become a very popular procedure with predictable results. Sinus floor augmentation procedures are generally carried out using autologous bone grafts, bone substitutes, or composites of bone and bone substitutes. However, the inherent limitations associated with each of these, have directed the attention of investigators to new technologies like bone tissue engineering. Bone marrow stromal cells have been regarded as multi-potent cells residing in bone marrow. These cells can be harvested from a person, multiplied outside his body using bioengineering principles and technologies and later introduced into a tissue defect. We present a case where tissue-engineered autologous osteoblasts were used along with demineralized freeze-dried bone for sinus floor augmentation.

  13. TGF-β/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis.

    Science.gov (United States)

    Wang, Shuang; Meng, Xiao-Ming; Ng, Yee-Yung; Ma, Frank Y; Zhou, Shuang; Zhang, Yang; Yang, Chen; Huang, Xiao-Ru; Xiao, Jun; Wang, Ying-Ying; Ka, Shuk-Man; Tang, Yong-Jiang; Chung, Arthur C K; To, Ka-Fai; Nikolic-Paterson, David J; Lan, Hui-Yao

    2016-02-23

    Myofibroblasts are a main cell-type of collagen-producing cells during tissue fibrosis, but their origins remains controversial. While bone marrow-derived myofibroblasts in renal fibrosis has been reported, the cell origin and mechanisms regulating their transition into myofibroblasts remain undefined. In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction. The MMT cells were a major source of collagen-producing fibroblasts in the fibrosing kidney, accounting for more than 60% of α-SMA+ myofibroblasts. The MMT process occurred predominantly within M2-type macrophages and was regulated by TGF-β/Smad3 signalling as deletion of Smad3 in the bone marrow compartment of GFP+ chimeric mice prevented the M2 macrophage transition into the MMT cells and progressive renal fibrosis. In vitro studies in Smad3 null bone marrow macrophages also showed that Smad3 was required for TGF-β1-induced MMT and collagen production. In conclusion, we have demonstrated that bone marrow-derived fibroblasts originate from the monocyte/macrophage population via a process of MMT. This process contributes to progressive renal tissue fibrosis and is regulated by TGF-β/Smad3 signalling.

  14. Enhancement of albumin expression in bone tissues with healing rat fractures.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Igarashi, Aki; Misawa, Hiroyuki; Tsurusaki, Yoshinori

    2003-05-15

    The characterization of 66 kDa protein molecule, a major protein component which is produced from femoral-diaphyseal tissues with fracture healing (Igarashi and Yamaguchi [2002] Int. J. Mol. Med. 9:503-508), was investigated. Weaning rats were killed at 7 and 14 days after femoral fracture. When the femoral-diaphyseal tissues with fracture healing were cultured for 48 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein molecule of approximately 66 kDa was markedly increased in culture medium from bone tissues with fracture healing. N-terminal sequencing of 66 kDa protein indicated that its N-terminus was identical to that of rat albumin. Western blot analysis of medium 66 kDa protein showed expression of albumin. This expression was significantly enhanced by fracture healing. The expression of albumin was seen in the diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues of rat femur. When the femoral-diaphyseal tissues obtained at 7 days after femoral fracture were cultured in a serum-free medium containing either vehicle, parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or zinc acexamate (10(-4) M), medium albumin was significantly increased in the presence of those bone-stimulating factors. The addition of albumin (0.5 or 1.0 mg/ml of medium) caused a significant increase in calcium and deoxyribonucleic acid contents in the femoral-diaphyseal and -metaphyseal tissues obtained from normal rats in vitro. The present study demonstrates that fracture healing induces a remarkable production of albumin which is a major protein component produced from femoral-diaphyseal tissues of rats, and that albumin has an anabolic effect on bone components.

  15. Mineralization of human bone tissue under hypokinesia and physical exercise with calcium supplements

    Science.gov (United States)

    Zorbas, Yan G.; Verentsov, Grigori E.; Abratov, Nikolai I.

    It has been suggested that physical exercise and calcium supplements may be used to prevent demineralization of bone tissue under hypokinesia (diminished muscular activity). Thus, the aim of this study was to determine mineral content of bones of 12 physically healthy men aged 19-24 years under 90 days of hypokinesia and intensive physical exercise (PE) with calcium lactate (C) supplements. They were divided into experimental and control groups with 6 men in each. The experimental group of men were subjected to hypokinesia (HK) and intensive PE and took 650 mg C 6 times per day; the control group was placed under pure HK, i.e. without the use of any preventive measures. The mineral content of different bone tissues was measured with a densitometric X-ray method in milligrams of calcium per 1 mm 3 before and after exposure to HK. The level of bone density of the examined bone tissues decreased by 7-9% and 5-7% for the control and experimental groups of men, respectively. A statistical analysis revealed that the reduction of bone mineralization was significant with P human organisms, since the entire animal kingdom had been formed in an environment of high motor activity which left its imprint on the evolution, structure, function and behaviour of animals and men. The impossibility of the body tissues to retain optimum amounts of fluid and electrolytes is the dominant hypokinetic effect.

  16. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering.

    Science.gov (United States)

    Gao, Xiang; Zhang, Xiaohong; Song, Jinlin; Xu, Xiao; Xu, Anxiu; Wang, Mengke; Xie, Bingwu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2015-01-01

    The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.

  17. Low-intensity pulsed ultrasound prompts tissue-engineered bone formation after implantation surgery

    Institute of Scientific and Technical Information of China (English)

    Wang Juyong; Wang Juqiang; Asou Yoshinori; Paul Fu; Shen Huiliang; Chen Jiani; Sotome Shinichi

    2014-01-01

    Background A practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts.Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds,enhanced production of bone marrow cells,and improved tissue-engineered bone formation.The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells (BMSCs).Methods BMSCs/β-tricalcium phosphate (β-TCP) composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound (LIPUS) treatment group and a control group.These implants were harvested at 5,10,25,and 50 days after implantation.The samples were then biomechanically tested and analyzed for alkaline phosphate (ALP) activity and osteocalcin (OCN) content and were also observed by light microscopy.Results The levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group.Histomorphometric analysis revealed a greater degree of soft tissue repair,increased blood flow,better angiogenesis,and more extensive bone formation in the LIPUS groups than in the controls.No significant difference in the compressive strength was found between the two groups.Conclusion LIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β3-TCP composites.

  18. Methods for demonstration of enzyme activity in muscle fibres at the muscle/bone interface in demineralized tissue

    DEFF Research Database (Denmark)

    Kirkeby, S; Vilmann, H

    1981-01-01

    A method for demonstration of activity for ATPase and various oxidative enzymes (succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase) in muscle/bone sections of fixed and demineralized tissue has been developed. It was found that it is possible to preserve...... with the aid of a mapping of presence of phosphomonoesterases on bone surfaces, the method may be used to study possible biochemical interactions between bone and muscle tissue at the muscle/bone interface....

  19. Biphasic calcium phosphate–casein bone graft fortified with Cassia occidentalis for bone tissue engineering and regeneration

    Indian Academy of Sciences (India)

    B Santhosh Kumar; T Hemalatha; R Deepachitra; R Narasimha Raghavan; P Prabu; T P Sastry

    2015-02-01

    Research on traditional herbs is gaining momentum owing to their potent medical properties, among which Cassia occidentalis (CO) is a promising herb, with osteogenic potential. The study investigates the efficacy of CO extract incorporated biphasic calcium phosphate as an osteoinductive material. Prepared bone implants were characterized physico-chemically using FT-IR, TGA, XRD, SEM and EDX. The implants were analysed further for mechanical and biological properties. The results revealed that CO extract-incorporated bone implants possessed better compression strength and it was able to induce proliferation and enhance alkaline phosphatase activity in SaOS-2 cells. The implant proves to be promising for bone tissue engineering, and hence it demands further in vivo evaluation.

  20. Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

    Science.gov (United States)

    Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

    2017-10-02

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

  1. Optical detection of carotenoid antioxidants in human bone and surrounding tissue.

    Science.gov (United States)

    Ermakov, Igor V; Ermakova, Maia R; Rosenberg, Thomas D; Gellermann, Werner

    2013-11-01

    Carotenoids are known to play an important role in health and disease state of living human tissue based on their antioxidant and optical filtering functions. In this study, we show that carotenoids exist in human bone and surrounding fatty tissue both in significant and individually variable concentrations. Measurements of biopsied tissue samples with molecule-specific Raman spectroscopy and high-performance liquid chromatography reveal that all carotenoids that are known to exist in human skin are also present in human bone. This includes all carotenes, lycopene, β-cryptoxanthin, lutein, and zeaxanthin. We propose quantitative reflection imaging as a noncontact optical method suitable for the measurement of composite carotenoid levels in bone and surrounding tissue exposed during open surgeries such as total knee arthroplasty, and as a proof of concept, demonstrate carotenoid measurements in biopsied bone samples. This will allow one to establish potential correlations between internal tissue carotenoid levels and levels in skin and to potentially use already existing optical skin carotenoid tests as surrogate marker for bone carotenoid status.

  2. Bone Morphogenetic Protein-2 Nonviral Gene Therapy in a Goat Iliac Crest Model for Bone Formation

    NARCIS (Netherlands)

    Loozen, Loek D.; van der Helm, Yvonne J. M.; Oner, F. Cumhur; Dhert, W.J.A.; Kruyt, Moyo C.; Alblas, Jacqueline

    2015-01-01

    Treatment and reconstruction of large bone defects, delayed unions, and nonunions is challenging and has resulted in an ongoing search for novel tissue-engineered therapies. Bone morphogenetic protein-2 (BMP-2) gene therapy is a promising strategy to provide sustained production of BMP-2 locally. Al

  3. Ready to Use Tissue Construct for Military Bone & Cartilage Trauma

    Science.gov (United States)

    2014-10-01

    supplied cell- permeable green fluorescent dye (Ex/Em = 488/518 nm) and propidium iodide (PI), a cell non- permeable red fluorescent dye (Ex/Em = 488/615...fixation is commonly used for forearm bone fractures. For femur and tibia, intramedullary nailing is a common choice of internal fixation. For the...humerus, both plate and screws and intramedullary nailing are used. However, for skeletal defects following resection of malignant tumors, intramedullary

  4. Determination of the relationship between collagen cross-links and the bone-tissue stiffness in the porcine mandibular condyle.

    Science.gov (United States)

    Willems, Nop M B K; Mulder, Lars; Bank, Ruud A; Grünheid, Thorsten; den Toonder, Jaap M J; Zentner, Andrej; Langenbach, Geerling E J

    2011-04-07

    Although bone-tissue stiffness is closely related to the degree to which bone has been mineralized, other determinants are yet to be identified. We, therefore, examined the extent to which the mineralization degree, collagen, and its cross-links are related to bone-tissue stiffness. A total of 50 cancellous and cortical bone samples were derived from the right mandibular condyles of five young and five adult female pigs. The degree of mineralization of bone (DMB) was assessed using micro-computed tomography. Using high-performance liquid chromatography, we quantified the collagen content and the number of cross-links per collagen molecule of two enzymatic cross-links: hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), and one non-enzymatic cross-link: pentosidine (Pen). Nanoindentation was used to assess bone-tissue stiffness in three directions, and multiple linear regressions were used to calculate the correlation between collagen properties and bone-tissue stiffness, with the DMB as first predictor. Whereas the bone-tissue stiffness of cancellous bone did not differ between the three directions of nanoindentation, or between the two age groups, cortical bone-tissue stiffness was higher in the adult tissue. After correction for DMB, the cross-links studied did not increase the explained variance. In the young group, however, LP significantly improved the explained variance in bone-tissue stiffness. Approximately half of the variation in bone-tissue stiffness in cancellous and cortical bone was explained by the DMB and the LP cross-links and thus they cannot be considered the sole determinants of the bone-tissue stiffness.

  5. Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonggang, E-mail: chenzg@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Kang, Lingzhi [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Meng, Qing-Yuan [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, Huanye [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Wang, Zhaoliang [Jinan Military General Hospital of PLA, Jinan 250031 (China); Guo, Zhongwu, E-mail: zwguo@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Cui, Fu-Zhai, E-mail: cuifz@mail.tsinghua.edu.cn [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2014-12-01

    The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials.

  6. Multiple verification in computational modeling of bone pathologies

    CERN Document Server

    Liò, Pietro; Paoletti, Nicola; 10.4204/EPTCS.67.8

    2011-01-01

    We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the...

  7. Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

    Science.gov (United States)

    Hambli, Ridha

    2014-01-01

    Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone

  8. Correlation Between Bone and Soft Tissue Thickness in Maxillary Anterior Teeth

    Directory of Open Access Journals (Sweden)

    Nasrin Esfahanizadeh

    2016-12-01

    Full Text Available Objectives: The purpose of this study was to determine buccal bone and soft tissue thicknesses and their correlation in the maxillary anterior region using cone beam computed tomography (CBCT.Materials and Methods: In this cross sectional study, 330 sound maxillary incisors in 60 patients with a mean age of 37.5 years were assessed by CBCT scans. For better visualization of soft tissue, patients were asked to use plastic retractors in order to retract their lips and cheeks away from the gingival tissue before taking the scans. Measurements were made in three different positions: at the crest and at 2 and 5mm apical to the crest. The cementoenamel junction‒crest distance was measured. for data analyses, the Pearson’s correlation coefficient, ANOVA and intraclass correlation coefficient were used.Results: There were mildly significant linear associations between labial soft tissue and bone thickness in the canines and incisors (r<0.40, P<0.05, but no association was found for the lateral incisors. The mean thickness of buccal bone differed significantly in the maxillary anterior teeth, being greater for the lateral incisors (P<0.05. For soft tissue thickness, the results were the same, and the least thickness was recorded for the canines. There was a mild association between labial soft tissue and bone thickness in canines and incisors (r=0.2, P=0.3, but no such linear association was seen for the lateral incisors.Conclusions: The mean thickness of buccal bone and soft tissue in the anterior maxilla was <1mm and there was a mild linear correlation between them.Keywords: Facial Bones; Cone-Beam Computed Tomography; Maxilla; Esthetics, Dental

  9. Bone tissue incorporates in vitro gallium with a local structure similar to gallium-doped brushite.

    Science.gov (United States)

    Korbas, M; Rokita, E; Meyer-Klaucke, W; Ryczek, J

    2004-01-01

    During mineral growth in rat bone-marrow stromal cell cultures, gallium follows calcium pathways. The dominant phase of the cell culture mineral constitutes the poorly crystalline hydroxyapatite (HAP). This model system mimics bone mineralization in vivo. The structural characterization of the Ga environment was performed by X-ray absorption spectroscopy at the Ga K-edge. These data were compared with Ga-doped synthetic compounds (poorly crystalline hydroxyapatite, amorphous calcium phosphate and brushite) and with strontium-treated bone tissue, obtained from the same culture model. It was found that Sr(2+) substitutes for Ca(2+) in the HAP crystal lattice. In contrast, the replacement by Ga(3+) yielded a much more disordered local environment of the probe atom in all investigated cell culture samples. The coordination of Ga ions in the cell culture minerals was similar to that of Ga(3+), substituted for Ca(2+), in the Ga-doped synthetic brushite (Ga-DCPD). The Ga atoms in the Ga-DCPD were coordinated by four oxygen atoms (1.90 A) of the four phosphate groups and two oxygen atoms at 2.02 A. Interestingly, the local environment of Ga in the cell culture minerals was not dependent on the onset of Ga treatment, the Ga concentration in the medium or the age of the mineral. Thus, it was concluded that Ga ions were incorporated into the precursor phase to the HAP mineral. Substitution for Ca(2+ )with Ga(3+) distorted locally this brushite-like environment, which prevented the transformation of the initially deposited phase into the poorly crystalline HAP.

  10. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue.

    Science.gov (United States)

    Shi, Yan-Chuan; Baldock, Paul A

    2012-02-01

    Skeletal research is currently undergoing a period of marked expansion. The boundaries of "bone" research are being re-evaluated and with this, a growing recognition of a more complex and interconnected biology than previously considered. One aspect that has become the focus of particular attention is the relationship between bone and fat homeostasis. Evidence from a number of avenues indicates that bone and adipose regulation are both related and interdependent. This review examines the neuropeptide Y (NPY) system, known to exert powerful control over both bone and fat tissue. The actions of this system are characterized by signaling both within specific nuclei of the hypothalamus and also the target tissues, mediated predominantly through two G-protein coupled receptors (Y1 and Y2). In bone tissue, elevated NPY levels act consistently to repress osteoblast activity. Moreover, both central Y2 receptor and osteoblastic Y1 receptor signaling act similarly to repress bone formation. Conversely, loss of NPY expression or receptor signaling induces increased osteoblast activity and bone mass in both cortical and cancellous envelopes. In fat tissue, NPY action is more complex. Energy homeostasis is powerfully altered by elevations in hypothalamic NPY, resulting in increases in fat accretion and body-wide energy conservation, through the action of locally expressed Y1 receptors, while local Y2 receptors act to inhibit NPY-ergic tone. Loss of central NPY expression has a markedly reduced effect, consistent with a physiological drive to promote fat accretion. In fat tissue, NPY and Y1 receptors act to promote lipogenesis, consistent with their roles in the brain. Y2 receptors expressed in adipocytes also act in this manner, showing an opposing action to their role in the hypothalamus. While direct investigation of these processes has yet to be completed, these responses appear to be interrelated to some degree. The starvation-based signal of elevated central NPY inducing

  11. Imaging technologies for preclinical models of bone and joint disorders.

    Science.gov (United States)

    Tremoleda, Jordi L; Khalil, Magdy; Gompels, Luke L; Wylezinska-Arridge, Marzena; Vincent, Tonia; Gsell, Willy

    2011-07-29

    Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy.

  12. Effect of Chenopodium ambrosioides on the healing process of the in vivo bone tissue.

    Science.gov (United States)

    Penha, Elizandra Silva da; Lacerda-Santos, Rogério; Carvalho, Maria Goretti Freire de; Oliveira, Patrícia Teixeira de

    2017-07-25

    The focus of this double-blind randomized study was on evaluating the effect of an aqueous extract of Mastruz (Chenopodium ambrosioides L.) on the bone repair process in vivo. In total, 36 male Wistar rats were randomly selected for this study, and divided into 3 groups (n = 12): Group HS (Hemostatic Sponge), Group SM (Hemostatic Sponge with Mastruz) and Group BC (Blood Clot). In each animal, bone defects measuring 2 mm in diameter were performed in both tibias for placement of the substances. After 3 and 10 days, the animals were sacrificed, and the tissues were analyzed under an optical microscope relative to the following events: inflammatory infiltrate; necrosis; young fibroblasts; osteoclastic and osteoblastic activity; endosteal and periosteal bone formation; and bone repair. The results were assessed by using Kruskal-Wallis and Mann-Whitney tests (p < .05). Inflammatory infiltrate demonstrated difference between Groups SM and BC in the time interval of 3 days (p = .004); an event related to the presence of the fibrin sponge and liquid of the extract, which induced a foreign body initial reaction. The presence of young fibroblasts (p = .003), osteoclastic (p = .003), and osteoblastic (p = .020) activity was statistically significant between Groups HS and BC in the time interval of 10 days; performance was related to the presence of the sponge within bone. As regards injured bone tissue repair, Group SM demonstrated a higher level of regenerative capacity (p = 0.004), due to a larger quantities of endosteal and periosteal bone formation, demonstrated in Group SM. The aqueous extract of mastruz stimulated bone neoformation, presenting wound closure with bone tissue at the end of 10 days. © 2017 Wiley Periodicals, Inc.

  13. Augmentation of the rat jaw with autogeneic cortico-cancellous bone grafts and guided tissue regeneration.

    Science.gov (United States)

    Donos, Nikolaos; Kostopoulos, Lambros; Karring, Thorkild

    2002-04-01

    The aim of the present study was to evaluate the effect of augmenting the maxillary alveolar ridge and the lateral aspect of the mandible with onlay autogeneic cortico-cancellous bone grafts that were covered with e-PTFE membranes. The experiment was carried out in 51 rats. In 15 rats, the edentulous maxillary jaw between the incisor and the first molar was augmented by means of an autogeneic ischiac bone graft that was fixed with a gold-coated microimplant. In one side, the graft was covered with an e-PTFE membrane, while the other side, which served as control, was treated without a membrane. In the other 36 rats, the lateral aspect of the mandible was augmented in both sides by means of an autogeneic ischiac bone graft that was fixed with a gold-coated or a titanium microimplant. In one side, the augmented area was covered with an e-PTFE membrane, while the contralateral side was treated without a membrane. Histological analysis at 60, 120 and 180 days after augmentation of the maxilla showed that, in the case of the test sites (where most of the membranes were either exposed or lost), the bone grafts presented extensive resorption and there was a lack of bone continuity between the graft and the recipient site. Similar findings were made at the non-membrane-treated control sides. In the case of augmentation of the mandible with membranes, the bone grafts were not resorbed, but were integrated into newly formed bone at the recipient site. In the control sides, the grafts presented varying degrees of resorption and integration into the recipient bone. It is concluded that, in comparison to bone grafting alone, onlay ischiac bone grafting combined with guided tissue regeneration eliminates the risk of bone graft resorption and ensures integration of the graft into newly formed bone at the recipient site, provided that closure of the operated area can be maintained during healing.

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

    Science.gov (United States)

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2014-09-01

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

  15. Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

    Science.gov (United States)

    Chen, Guobao; Lv, Yonggang

    2015-01-01

    Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

  16. Development of a realistic in vivo bone metastasis model of human renal cell carcinoma.

    Science.gov (United States)

    Valta, Maija P; Zhao, Hongjuan; Ingels, Alexandre; Thong, Alan E; Nolley, Rosalie; Saar, Matthias; Peehl, Donna M

    2014-06-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.

  17. Fabrication of nanocrystalline hydroxyapatite doped degradable composite hollow fiber for guided and biomimetic bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Ning [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Nichols, Heather L. [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Tylor, Shila [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Wen Xuejun [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States)]. E-mail: xjwen@clemson.edu

    2007-04-15

    Natural bone tissue possesses a nanocomposite structure interwoven in a three-dimensional (3-D) matrix, which plays critical roles in conferring appropriate physical and biological properties to the bone tissue. Single type of material may not be sufficient to mimic the composition, structure and properties of native bone, therefore, composite materials consisting of both polymers, bioceramics, and other inorganic materials have to be designed. Among a variety of candidate materials, polymer-nanoparticle composites appear most promising for bone tissue engineering applications because of superior mechanical properties, improved durability, and surface bioactivity when compared with conventional polymers or composites. The long term objective of this project is to use highly aligned, bioactive, biodegradable scaffold mimicking natural histological structure of human long bone, and to engineer and regenerate human long bone both in vitro and in vivo. In this study, bioactive, degradable, and highly permeable composite hollow fiber membranes (HFMs) were fabricated using a wet phase phase-inversion approach. The structure of the hollow fiber membranes was examined using scanning electron microscopy (SEM); degradation behavior was examined using weigh loss assay, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC); and bioactivity was evaluated with the amount of calcium deposition from the culture media onto HFM surface. Doping PLGA HFMs with nanoHA results in a more bioactive and slower degrading HFM than pure PLGA HFMs.

  18. Experimental and numerical analysis of Izod impact test of cortical bone tissue

    Science.gov (United States)

    Abdel-Wahab, A. A.; Silberschmidt, V. V.

    2012-05-01

    Bones can only sustain loads until a certain limit, beyond which they fail. Usually, the reasons for bone fracture are traumatic falls, sports injuries, and engagement in transport or industrial accidents. A proper treatment of bones and prevention of their fracture can be supported by in-depth understanding of deformation and fracture behavior of this tissue in such dynamic events. In this paper, a combination of experimental and numerical analysis was carried out in order to comprehend the fracture behavior of cortical bone tissue. Experimental tests were performed to study the transient dynamic behavior of cortical bone tissue under impact bending loading. The variability of absorbed energy for different cortex positions and notch depths was studied using Izod impact tests. Also, Extended Finite-Element Method implemented into the commercial finite-element software Abaqus was used to simulate the crack initiation and growth processes in a cantilever beam of cortical bone exposed to impact loading using the Izod loading scheme. The simulation results show a good agreement with the experimental data.

  19. Mathematical Model for the Mineralization of Bone

    Science.gov (United States)

    Martin, Bruce

    1994-01-01

    A mathematical model is presented for the transport and precipitation of mineral in refilling osteons. One goal of this model was to explain calcification 'halos,' in which the bone near the haversian canal is more highly mineralized than the more peripheral lamellae, which have been mineralizing longer. It was assumed that the precipitation rate of mineral is proportional to the difference between the local concentration of calcium ions and an equilibrium concentration and that the transport of ions is by either diffusion or some other concentration gradient-dependent process. Transport of ions was assumed to be slowed by the accumulation of mineral in the matrix along the transport path. ne model also mimics bone apposition, slowing of apposition during refilling, and mineralization lag time. It was found that simple diffusion cannot account for the transport of calcium ions into mineralizing bone, because the diffusion coefficient is two orders of magnitude too low. If a more rapid concentration gradient-driven means of transport exists, the model demonstrates that osteonal geometry and variable rate of refilling work together to produce calcification halos, as well as the primary and secondary calcification effect reported in the literature.

  20. A predictive bone drilling force model for haptic rendering with experimental validation using fresh cadaveric bone.

    Science.gov (United States)

    Lin, Yanping; Chen, Huajiang; Yu, Dedong; Zhang, Ying; Yuan, Wen

    2017-01-01

    Bone drilling simulators with virtual and haptic feedback provide a safe, cost-effective and repeatable alternative to traditional surgical training methods. To develop such a simulator, accurate haptic rendering based on a force model is required to feedback bone drilling forces based on user input. Current predictive bone drilling force models based on bovine bones with various drilling conditions and parameters are not representative of the bone drilling process in bone surgery. The objective of this study was to provide a bone drilling force model for haptic rendering based on calibration and validation experiments in fresh cadaveric bones with different bone densities. Using a commonly used drill bit geometry (2 mm diameter), feed rates (20-60 mm/min) and spindle speeds (4000-6000 rpm) in orthognathic surgeries, the bone drilling forces of specimens from two groups were measured and the calibration coefficients of the specific normal and frictional pressures were determined. The comparison of the predicted forces and the measured forces from validation experiments with a large range of feed rates and spindle speeds demonstrates that the proposed bone drilling forces can predict the trends and average forces well. The presented bone drilling force model can be used for haptic rendering in surgical simulators.

  1. Profiling Osteogenic microRNAs For RNAi-Functionalization Of Scaffolds In Bone Tissue Engineering

    DEFF Research Database (Denmark)

    Chang, Chi-Chih (Clare); Chen, Li; Venø, Morten Trillingsgaard

    is limited and grafts are required to assist in bone repair. The use of allografts can cause immunological complications, whilst autografts subject the patient to two surgeries. Bone tissue engineering is a multidisciplinary field encompassing material science, medicine, chemistry and molecular biology aimed...... both miRNAs that have been reported previously and many novel miRNAs with potent osteogenic capabilities. For tissue engineering applications, we then functionalized scaffolds with the miRNAs we identified and observed an increase in osteogenic capabilities in our 3D cultures. Our findings depicted...... the miRNA expression landscape as mesenchymal stem cells underwent osteogenic differentiation. We also highlight the potency of miRNAs as biological therapeutics in bone tissue engineering....

  2. Cell-free scaffolds with different stiffness but same microstructure promote bone regeneration in rabbit large bone defect model.

    Science.gov (United States)

    Chen, Guobao; Yang, Li; Lv, Yonggang

    2016-04-01

    To promote bone healing, bone repair biomaterials are increasingly designed to incorporate growth factors. However, the impact of matrix mechanics of cell-free scaffold independent of microstructure on the osteogenic differentiation of endogenous osteoprogenitor cells orchestrating bone repair and regeneration remains not to be fully understood. In our recent study, three-dimensional (3D) scaffolds with different stiffness but same microstructure have been successfully fabricated by coating decellularized bone with collagen/hydroxyapatite (HA) mixture with different collagen rations. It has been demonstrated that the scaffold with optimal stiffness can induce the osteogenic differentiation of MSCs in vitro and in the subcutaneous tissue. The present in vivo study further investigated the repair efficiency of these scaffolds in a rabbit radius with a critical-sized segmental defect model and its potential mechanism. Micro-computed tomography (μ-CT), X-ray and histological analysis were carried out to evaluate the repair capacity of these scaffolds. The results demonstrated that the cell-free scaffold with optimal stiffness incorporation of endogenous osteoprogenitor cells significantly promoted the repair and reconstruction quality of mass bone defect. One of the crucial mechanisms was that hypoxia and stromal cell-derived factor-1α (SDF-1α) mediated mesenchymal stem cells (MSCs) migration by which matrix mechanics exerted influence on bone fracture healing. These findings suggested that only modulating the matrix stiffness of cell-free scaffold can be one of the most attractive strategies for promoting the progression of bone healing.

  3. Bone regeneration by octacalcium phosphate collagen composites in a dog alveolar cleft model.

    Science.gov (United States)

    Matsui, K; Matsui, A; Handa, T; Kawai, T; Suzuki, O; Kamakura, S; Echigo, S

    2010-12-01

    Octacalcium phosphate (OCP) and porcine atelocollagen sponge composites (OCP/Col) markedly enhanced bone regeneration in a rat cranial defect model. To assess clinical application, the authors examined whether OCP/Col would enhance bone regeneration in an alveolar cleft model in an adult dog, which was assumed to reflect patients with alveolar cleft. Disks of OCP/Col or collagen were implanted into the defect and bone regeneration by OCP/Col or collagen was investigated 4 months after implantation. Macroscopically, the OCP/Col-treated alveolus was obviously augmented and occupied by radio-opacity, and the border between the original bone and the defect was indistinguishable. Histological analysis revealed it was filled and bridged with newly formed bone; a small quantity of the remaining implanted OCP was observed. X-ray diffraction patterns of the area of implanted OCP/Col indicated no difference from those of dog bone. In the collagen-treated alveolus, the hollowed alveolus was mainly filled with fibrous connective tissue, and a small amount of new bone was observed at the defect margin. These results suggest that bone was obviously repaired when OCP/Col was implanted into the alveolar cleft model in a dog, and OCP/Col would be a significant bone regenerative material to substitute for autogeneous bone.

  4. Substituted Borosilicate Glasses with Improved Osteogenic Capacity for Bone Tissue Engineering.

    Science.gov (United States)

    Fernandes, João S; Gentile, Piergiorgio; Crawford, Aileen; Pires, Ricardo A; Hatton, Paul V; Reis, Rui L

    2017-03-27

    Borosilicate bioactive glasses (BBGs) have shown the capacity to promote higher formation of new bone when compared with silicate bioactive glasses. Herein, we assessed the capacity of BBGs to induce osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) as a function of their substituted divalent cations (Mg(2+), Ca(2+), Sr(2+)). To this purpose, we synthesized BBG particles by melt quenching. The cell viability, proliferation, and morphology (i.e., PrestoBlue(®), PicoGreen(®), and DAPI and Phalloidin stainings, respectively), as well as protein expression (i.e., alkaline phosphatase, ALP; osteopontin, OP; and osteocalcin, OC), of BM-MSCs in contact with BBGs were evaluated for 21 days. We observed an enhanced expression of bone-specific proteins (ALP, OP, and OC) and high mineralization of BM-MSCs under BBG-Mg and BBG-Sr-conditioned osteogenic media for concentrations of 20 and 50 mg/mL with low cytotoxic effects. Moreover, BBG-Sr, at a concentration of 50 mg/mL, was able to increase the mineralization and expression of the same bone-specific proteins even under basal medium conditions. These results indicated that the proposed BBGs improved osteogenic differentiation of BM-MSCs, therefore showing their potential as relevant biomaterials for bone tissue regeneration, not only by bonding to bone tissue but also by stimulating new bone formation.

  5. Systemic drug delivery systems for bone tissue regeneration- a mini review.

    Science.gov (United States)

    Xinluan, Wang; Yuxiao, Lai; Helena, Ng HueiLeng; Zhijun, Yang; Ling, Qin

    2015-01-01

    Musculoskeletal metabolic diseases such as osteoporosis have become the major public health problems worldwide in our aging society. Pharmaceutical therapy is one of the approaches to prevent and treat related medical conditions. Most of the clinically used anti-osteoporotic drugs are administered systemically and have demonstrated some side effects in non-skeletal tissues. One of the innovative approaches to prevent potential adverse effects is the development of bone-targeting drug delivery technologies that not only minimizes the systemic toxicity but also improves the pharmacokinetic profile and therapeutic efficacy of chemical drugs. This paper reviews the currently available bone targeting drug delivery systems with emphasis as bone-targeting moieties, including the bonesurface- site-specific (bone formation dominant or bone resorption dominant) and cell-specific moieties. In addition, the connections of drug-bone-targeting moieties-carrier are also summarized, and the newly developed liposomes and nanoparticles are discussed for their potential use and main challenges in delivering therapeutic agents to bone tissue. As a rapid-developing biotechnology, systemic bonetargeting delivery system is promising but still in its infancy where challenges are ahead of us, including the stability and the toxicity issues, especially to fulfill the regulatory requirement to realize bench-to-bedside translation. Newly developed biomaterials and technologies with potential for safer and more effective drug delivery require multidisciplinary collaborations with preclinical and clinical scientists that are essential to facilitate their clinical applications.

  6. Final Report for completed IPP Project:"Development of Plasma Ablation for Soft Tissue and Bone Surgery"

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Ian

    2009-09-01

    ArthroCare is a medical device company that develops, manufactures, and markets an advanced surgical tool, a plasma electro-surgical system for cutting and removing tissue. The hand-held electrical discharge device produces plasma in a biocompatible conductive fluid and tissue to which it is applied during surgery. Its products allow surgeons to operate with increased precision and accuracy, limiting damage to surrounding tissue thereby reducing pain and speeding recovery for the patient. In the past, the design of ArthfoCare's plasma wands has been an empirical undertaking. One goal of this R&D program was to put the phenomena involved on a sound scientific footing, allowing optimization of existing plasma based electro-surgery system technology, and the design and manufacture of new and improved kinds of scalpels, in particular for the surgical cutting of bone. Another important related goal of the program was to develop, through an experimental approach, new plasma wand approaches to the cutting ('shaving') of hard bone tissue. The goals of the CRADA were accomplished - computer models were used to predict important parameters of the plasma discharge and the bone environment, and several different approaches to bone-shaving were developed and demonstrated. The primary goal of the project was to develop and demonstrate an atmospheric-pressure plasma tool that is suitable for surgical use for shaving bone in humans. This goal was accomplished, in fact with several different alternative plasma approaches. High bone ablation speeds were measured. The use of probes ('plasma wand' - the surgical tool) with moving active electrodes was also explored, and there are advantages to this method. Another important feature is that the newly-exposed bone surface have only a very thin necrosis layer; this feature was demonstrated. This CRADA has greatly advanced our understanding of bone removal by atmospheric pressure plasmas in liquid, and puts Arthro

  7. 3D Tissue Scaffold Printing On Custom Artificial Bone Applications

    Directory of Open Access Journals (Sweden)

    Betül ALDEMİR

    2015-01-01

    Full Text Available Production of defect-matching scaffolds is the most critical step in custom artificial bone applications. Three dimensional printing (3DP is one of the best techniques particularly for custom designs on artificial bone applications because of the high controllability and design independency. Our long-term aim is to implant an artificial custom bone that is cultured with patient's own mesenchymal stem cells after determining defect architecture on patient's bone by using CT-scan and printing that defect-matching 3D scaffold with appropriate nontoxic materials. In this study, preliminary results of strength and cytotoxicity measurements of 3D printed scaffolds with modified calcium sulfate compositepowder (MCSCP were presented. CAD designs were created and MCSCP were printed by a 3D printer (3DS, Visijet, PXL Core. Some samples were covered with salt solution in order to harden the samples. MCSCP and salt coated MCSCP were the two experimental groups in this study. Cytotoxicity and mechanical experiments were performed after surface examination withscanning electron microscope (SEM and light microscope. Tension tests were performed for MCSCP and salt coated MCSCP samples. The 3D scaffolds were sterilized with ethylene oxide gas sterilizer, ventilated and conditioned with DMEM (10% FBS. L929 mouse fibroblast cells were cultured on scaffolds (3 repetitive and cell viability was determined using MTT analysis. According to the mechanical results, the MCSCP group stands until average 71,305 N, while salt coated MCSCP group stands until 21,328N. Although the strength difference between two groups is statistically significant (p=0.001, Mann-Whitney U, elastic modulus is not (MCSCP=1,186Pa, salt coated MCSCP=1,169Pa, p=0.445. Cell viability (MTT analysis results on day 1, 3, and 5 demonstrated thatscaffolds hadno toxic effect to the L929 mouse fibroblast cells. Consequently, 3D printed samples with MCSCP could potentially be a strong alternative

  8. Reduced tissue hardness of trabecular bone is associated with severe osteoarthritis.

    Science.gov (United States)

    Dall'Ara, Enrico; Ohman, Caroline; Baleani, Massimiliano; Viceconti, Marco

    2011-05-17

    This study investigated whether changes in hardness of human trabecular bone are associated with osteoarthritis. Twenty femoral heads extracted from subjects without musculoskeletal diseases (subject age: 49-83 years) and twenty femoral heads extracted from osteoarthritic subjects (subject age: 42-85 years) were tested. Sixty indentations were performed along the main trabecular direction of each sample at a fixed relative distance. Two microstructures were found on the indenting locations: packs of parallel-lamellae (PL) and secondary osteons (SO). A 25gf load was applied for 15s and the Vickers Hardness (HV) was assessed. Trabecular tissue extracted from osteoarthritic subjects was found to be about 13% less hard compared to tissue extracted from non-pathologic subjects. However, tissue hardness was not significantly affected by gender or age. The SO was 10% less hard than the PL for both pathologic and non-pathologic tissues. A hardness of 34.1HV for PL and 30.8HV for SO was found for the non-pathologic tissue. For osteoarthritic tissue, the hardness was 30.2HV for PL and 27.1HV for SO. In the bone tissue extracted from osteoarthritic subjects the occurrence of indenting a SO (28%) was higher than that observed in the non-pathological tissue (15%). Osteoarthritis is associated with reduced tissue hardness and alterations in microstructure of the trabecular bone tissue. Gender does not significantly affect trabecular bone hardness either in non-pathological or osteoarthritic subjects. A similar conclusion can be drawn for age, although a larger donor sample size would be necessary to definitively exclude the existence of a slight effect.

  9. 3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair.

    Science.gov (United States)

    Xu, Ning; Ye, Xiaojian; Wei, Daixu; Zhong, Jian; Chen, Yuyun; Xu, Guohua; He, Dannong

    2014-09-10

    The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load-bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects.

  10. Mechanical unloading of bone in microgravity reduces mesenchymal and hematopoietic stem cell-mediated tissue regeneration

    Directory of Open Access Journals (Sweden)

    E.A. Blaber

    2014-09-01

    Full Text Available Mechanical loading of mammalian tissues is a potent promoter of tissue growth and regeneration, whilst unloading in microgravity can cause reduced tissue regeneration, possibly through effects on stem cell tissue progenitors. To test the specific hypothesis that mechanical unloading alters differentiation of bone marrow mesenchymal and hematopoietic stem cell lineages, we studied cellular and molecular aspects of how bone marrow in the mouse proximal femur responds to unloading in microgravity. Trabecular and cortical endosteal bone surfaces in the femoral head underwent significant bone resorption in microgravity, enlarging the marrow cavity. Cells isolated from the femoral head marrow compartment showed significant down-regulation of gene expression markers for early mesenchymal and hematopoietic differentiation, including FUT1(−6.72, CSF2(−3.30, CD90(−3.33, PTPRC(−2.79, and GDF15(−2.45, but not stem cell markers, such as SOX2. At the cellular level, in situ histological analysis revealed decreased megakaryocyte numbers whilst erythrocytes were increased 2.33 fold. Furthermore, erythrocytes displayed elevated fucosylation and clustering adjacent to sinuses forming the marrow–blood barrier, possibly providing a mechanistic basis for explaining spaceflight anemia. Culture of isolated bone marrow cells immediately after microgravity exposure increased the marrow progenitor's potential for mesenchymal differentiation into in-vitro mineralized bone nodules, and hematopoietic differentiation into osteoclasts, suggesting an accumulation of undifferentiated progenitors during exposure to microgravity. These results support the idea that mechanical unloading of mammalian tissues in microgravity is a strong inhibitor of tissue growth and regeneration mechanisms, acting at the level of early mesenchymal and hematopoietic stem cell differentiation.

  11. Paper-based bioactive scaffolds for stem cell-mediated bone tissue engineering.

    Science.gov (United States)

    Park, Hyun-Ji; Yu, Seung Jung; Yang, Kisuk; Jin, Yoonhee; Cho, Ann-Na; Kim, Jin; Lee, Bora; Yang, Hee Seok; Im, Sung Gap; Cho, Seung-Woo

    2014-12-01

    Bioactive, functional scaffolds are required to improve the regenerative potential of stem cells for tissue reconstruction and functional recovery of damaged tissues. Here, we report a paper-based bioactive scaffold platform for stem cell culture and transplantation for bone reconstruction. The paper scaffolds are surface-engineered by an initiated chemical vapor deposition process for serial coating of a water-repellent and cell-adhesive polymer film, which ensures the long-term stability in cell culture medium and induces efficient cell attachment. The prepared paper scaffolds are compatible with general stem cell culture and manipulation techniques. An optimal paper type is found to provide structural, physical, and mechanical cues to enhance the osteogenic differentiation of human adipose-derived stem cells (hADSCs). A bioactive paper scaffold significantly enhances in vivo bone regeneration of hADSCs in a critical-sized calvarial bone defect. Stacking the paper scaffolds with osteogenically differentiated hADSCs and human endothelial cells resulted in vascularized bone formation in vivo. Our study suggests that paper possesses great potential as a bioactive, functional, and cost-effective scaffold platform for stem cell-mediated bone tissue engineering. To the best of our knowledge, this is the first study reporting the feasibility of a paper material for stem cell application to repair tissue defects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Scaffolds for Growth Factor Delivery as Applied to Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Keith A. Blackwood

    2012-01-01

    Full Text Available There remains a substantial shortfall in the treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue-engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors, which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However due to the cost and potential complications associated with growth factors, controlling the rate of release is an important design consideration when developing new bone tissue engineering strategies. This paper will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.

  13. Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    John G. Hardy

    2016-07-01

    Full Text Available Materials based on biodegradable polyesters, such as poly(butylene terephthalate (PBT or poly(butylene terephthalate-co-poly(alkylene glycol terephthalate (PBTAT, have potential application as pro-regenerative scaffolds for bone tissue engineering. Herein, the preparation of films composed of PBT or PBTAT and an engineered spider silk protein, (eADF4(C16, that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported. Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering.

  14. Baculovirus as a gene delivery vector for cartilage and bone tissue engineering.

    Science.gov (United States)

    Lin, Chin-Yu; Lu, Chia-Hsin; Luo, Wen-Yi; Chang, Yu-Han; Sung, Li-Yu; Chiu, Hsin-Yi; Hu, Yu-Chen

    2010-06-01

    Baculovirus is an effective vector for gene delivery into various mammalian cells, including chondrocytes and mesenchymal stem cells, and has been employed for diverse applications. By gene delivery and expression of the growth factor, recombinant baculovirus has been shown to modulate the differentiation state of the cells and stimulates the production of extracellular matrix and tissue formation, hence repairing the damaged cartilage and bone in vivo. This article reviews the studies pertaining to the applications of baculovirus-mediated gene delivery in cartilage and bone tissue engineering and discusses recent progress, future applications and potential hurdles.

  15. Composite Scaffolds Containing Silk Fibroin, Gelatin, and Hydroxyapatite for Bone Tissue Regeneration and 3D Cell Culturing.

    Science.gov (United States)

    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.

  16. Engineered polycaprolactone–magnesium hybrid biodegradable porous scaffold for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Hoi Man Wong

    2014-10-01

    Full Text Available In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone (PCL and magnesium (Mg micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150% by incorporating 29% Mg particles with the porosity of 74% using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236% when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.

  17. Engineered polycaprolactone-magnesium hybrid biodegradable porous scaffold for bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Hoi Man Wong; Paul K. Chu; Frankie K.L. Leung; Kenneth M.C. Cheung; Keith D.K. Luk; Kelvin W.K. Yeung

    2014-01-01

    In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone (PCL) and magnesium (Mg) micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150%by incorporating 29%Mg particles with the porosity of 74%using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236%when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.

  18. Ornamenting 3D printed scaffolds with cell-laid extracellular matrix for bone tissue regeneration.

    Science.gov (United States)

    Pati, Falguni; Song, Tae-Ha; Rijal, Girdhari; Jang, Jinah; Kim, Sung Won; Cho, Dong-Woo

    2015-01-01

    3D printing technique is the most sophisticated technique to produce scaffolds with tailorable physical properties. But, these scaffolds often suffer from limited biological functionality as they are typically made from synthetic materials. Cell-laid mineralized ECM was shown to be potential for improving the cellular responses and drive osteogenesis of stem cells. Here, we intend to improve the biological functionality of 3D-printed synthetic scaffolds by ornamenting them with cell-laid mineralized extracellular matrix (ECM) that mimics a bony microenvironment. We developed bone graft substitutes by using 3D printed scaffolds made from a composite of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) and mineralized ECM laid by human nasal inferior turbinate tissue-derived mesenchymal stromal cells (hTMSCs). A rotary flask bioreactor was used to culture hTMSCs on the scaffolds to foster formation of mineralized ECM. A freeze/thaw cycle in hypotonic buffer was used to efficiently decellularize (97% DNA reduction) the ECM-ornamented scaffolds while preserving its main organic and inorganic components. The ECM-ornamented 3D printed scaffolds supported osteoblastic differentiation of newly-seeded hTMSCs by upregulating four typical osteoblastic genes (4-fold higher RUNX2; 3-fold higher ALP; 4-fold higher osteocalcin; and 4-fold higher osteopontin) and increasing calcium deposition compared to bare 3D printed scaffolds. In vivo, in ectopic and orthotopic models in rats, ECM-ornamented scaffolds induced greater bone formation than that of bare scaffolds. These results suggest a valuable method to produce ECM-ornamented 3D printed scaffolds as off-the-shelf bone graft substitutes that combine tunable physical properties with physiological presentation of biological signals.

  19. Nanohydroxyapatite Effect on the Degradation, Osteoconduction and Mechanical Properties of Polymeric Bone Tissue Engineered Scaffolds

    Science.gov (United States)

    Salmasi, Shima; Nayyer, Leila; Seifalian, Alexander M.; Blunn, Gordon W.

    2016-01-01

    BACKGROUND Statistical reports show that every year around the world approximately 15 million bone fractures occur; of which up to 10% fail to heal completely and hence lead to complications of non-union healing. In the past, autografts or allografts were used as the “gold standard” of treating such defects. However, due to various limitations and risks associated with these sources of bone grafts, other avenues have been extensively investigated through which bone tissue engineering; in particular engineering of synthetic bone graft substitutes, has been recognised as a promising alternative to the traditional methods. METHODS A selective literature search was performed. RESULTS Bone tissue engineering offers unlimited supply, eliminated risk of disease transmission and relatively low cost. It could also lead to patient specific design and manufacture of implants, prosthesis and bone related devices. A potentially promising building block for a suitable scaffold is synthetic nanohydroxyapatite incorporated into synthetic polymers. Incorporation of nanohydroxyapatite into synthetic polymers has shown promising bioactivity, osteoconductivity, mechanical properties and degradation profile compared to other techniques previously considered. CONCLUSION Scientific research, through extensive physiochemical characterisation, in vitro and in vivo assessment has brought together the optimum characteristics of nanohydroxyapatite and various types of synthetic polymers in order to develop nanocomposites of suitable nature for bone tissue engineering. The aim of the present article is to review and update various aspects involved in incorporation of synthetic nanohydroxyapatite into synthetic polymers, in terms of their potentials to promote bone growth and regeneration in vitro, in vivo and consequently in clinical applications. PMID:28217213

  20. Effect of heat generation from bone cement on bone tissue in total knee arthroplasty; Jinko kansetsu okikaeji no one cement no hatsunetsu ga seitai soshiki ni oyobosu eikyo ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, M.; Uchida, T. [Kobe University, Kobe (Japan); Iwatsubo, T. [Kobe University, Kobe (Japan). Faculty of Engineering; Kurosawa, M.; Hashimoto, Y. [Kobe University, Kobe (Japan). Faculty of Medicine; Fukushima, H.

    1998-01-25

    Bone cement is often applied to fix the components in a surgical operation, such as TKA (total knee arthroplasty). In this paper, we consider the effect of heat generation from bone cement on bone tissue in TKA by using numerical simulation. First, we applied an axisymmetric model of tibia to finite element method and analyzed heat generation of bone cement. To confirm the results of analysis by experiment, we measured the temperature determined by 6 points i.e., 2 points each in component-cement interface, cement and bone-cement interface. As a result, the temperature determined by analysis agrees with that determined by experiment. Next, we proposed the evaluation formula of the bone necrosis. We constructed a bone necrosis map from the simulation. From the map, we found that the bone necrosis region was about 2 mm from the bone-cement interface. In addition, the bone necrosis is severe at the base of the tibial component. 7 refs., 15 figs., 3 tabs.

  1. Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma?

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    Boris Michael Holzapfel

    2013-01-01

    Full Text Available Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.

  2. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues.

    Science.gov (United States)

    Zhang, Gong; Yuan, Hai; Chen, Xianshuai; Wang, Weijun; Chen, Jianyu; Liang, Jimin; Zhang, Peng

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface.

  3. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues

    Directory of Open Access Journals (Sweden)

    Gong Zhang

    2016-01-01

    Full Text Available Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface.

  4. Soft tissues, areal bone mineral density and hip geometry estimates in active young boys: the PRO-BONE study.

    Science.gov (United States)

    Wilkinson, Kelly; Vlachopoulos, Dimitris; Klentrou, Panagiota; Ubago-Guisado, Esther; De Moraes, Augusto César Ferreira; Barker, Alan R; Williams, Craig A; Moreno, Luis A; Gracia-Marco, Luis

    2017-04-01

    Soft tissues, such as fat mass (FM) and lean mass (LM), play an important role in bone development but this is poorly understood in highly active youths. The objective of this study was to determine whether FM or LM is a stronger predictor of areal bone mineral density (aBMD) and hip geometry estimates in a group of physically active boys after adjusting for height, chronological age, moderate-to-vigorous physical activity (MVPA), FM, and LM. Participants included 121 boys (13.1 ± 1.0 years) from the PRO-BONE study. Bone mineral content (BMC) and aBMD were measured at total body, femoral neck and lumbar spine using dual-energy X-ray absorptiometry (DXA), and hip structural analysis was used to estimate bone geometry at the femoral neck. Body composition was assessed using DXA. The relationships of FM and LM with bone outcomes were analysed using simple and multiple linear regression analyses. Pearson correlation coefficients showed that total body (less head) aBMD was significantly correlated with LM but not FM. Multiple linear regression analyses showed that FM, after accounting for height, age, MVPA and LM had no significant relationship with aBMD or hip geometry estimates, except for arms aBMD. By contrast, there were positive associations between LM and most aBMD and hip geometry estimates, after accounting height, age, MVPA and FM. The results of this study suggest that LM, and not FM, is the stronger predictor of aBMD and hip geometry estimates in physically active boys. ClinicalTrials.gov ISRCTN17982776.

  5. Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

    Science.gov (United States)

    Caddeo, Silvia; Boffito, Monica; Sartori, Susanna

    2017-01-01

    In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and

  6. Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

    Directory of Open Access Journals (Sweden)

    Silvia Caddeo

    2017-07-01

    Full Text Available In the tissue engineering (TE paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart

  7. Preclinical mouse models for assessing axial compression of long bones during exercise.

    Science.gov (United States)

    Stadelmann, Vincent A; Brun, Julia; Bonnet, Nicolas

    2015-01-01

    The aim of this laboratory method is to describe two approaches for the investigation of bone responses to mechanical loading in mice in vivo. The first is running exercise, because it is easily translatable clinically, and the second is axial compression of the tibia, because it is precisely controllable. The effects of running exercise, and in general physical activity, on bone tissue have been shown to be both direct through mechanical loading (ground impact and muscle tension) and indirect through metabolic changes. Therefore, running exercise has been considered the most convenient preclinical model for demonstrating the general idea that exercise is good for bone health, either early in age for increasing peak bone mass or later in age by slowing down bone loss. However, numerous combinations of protocols have been reported, which makes it difficult to formulate a simple take-home message. This laboratory method also provides a detailed description of in vivo direct mechanical axial compression of the mouse tibia. The effects of mechanical loading depend on the force (strain), frequency, waveform and duration of application, and they range from bone anabolism with low bone remodeling, inducing lamellar bone accumulation, to bone catabolism with high bone remodeling, leading to microdamage, woven bone formation and bone loss. Direct in vivo loading models are extensively used to study mechanotransduction pathways, and contribute by this way to the development of new bone anabolism treatments. Although it is particularly difficult to assemble an internationally adopted protocol description, which would give reproducible bone responses, here we have attempted to provide a comprehensive guide for best practice in performing running exercise and direct in vivo mechanical loading in the laboratory.

  8. Effect of Combined Calcium Hydroxide and Accelerated Portland Cement on Bone Formation and Soft Tissue Healing in Dog Bone Lesions

    Directory of Open Access Journals (Sweden)

    Khorshidi H

    2015-09-01

    Full Text Available Statement of Problem: Recent literatures show that accelerated Portland cement (APC and calcium hydroxide Ca (OH2 may have the potential to promote the bone regeneration. However, certain clinical studies reveal consistency of Ca (OH2, as one of the practical drawbacks of the material when used alone. To overcome such inconvenience, the combination of the Ca (OH2 with a bone replacement material could offer a convenient solution. Objectives: To evaluate the soft tissue healing and bone regeneration in the periodontal intrabony osseous defects using accelerated Portland cement (APC in combination with calcium hydroxide Ca (OH2, as a filling material. Materials and Methods: Five healthy adult mongrel dogs aged 2-3 years old (approximately 20 kg in weight with intact dentition and healthy periodontium were selected for this study. Two one-wall defects in both mesial and distal aspects of the 3rd premolars of both sides of the mandible were created. Therefore, four defects were prepared in each dog. Three defects in each dog were randomly filled with one of the following materials: APC alone, APC mixed with Ca (OH2, and Ca (OH2 alone. The fourth defect was left empty (control. Upon clinical examination of the sutured sites, the amount of dehiscence from the adjacent tooth was measured after two and eight weeks, using a periodontal probe mesiodistally. For histometric analysis, the degree of new bone formation was estimated at the end of the eighth postoperative week, by a differential point-counting method. The percentage of the defect volume occupied by new osteoid or trabecular bone was recorded. Results: Measurement of wound dehiscence during the second week revealed that all five APCs had an exposure of 1-2 mm and at the end of the study all samples showed 3-4 mm exposure across the surface of the graft material, whereas the Ca (OH2, control, and APC + Ca (OH2 groups did not show any exposure at the end of the eighth week of the study. The most

  9. Effect of coating Straumann Bone Ceramic with Emdogain on mesenchymal stromal cell hard tissue formation.

    Science.gov (United States)

    Mrozik, Krzysztof Marek; Gronthos, Stan; Menicanin, Danijela; Marino, Victor; Bartold, P Mark

    2012-06-01

    Periodontal tissue engineering requires a suitable biocompatible scaffold, cells with regenerative capacity, and instructional molecules. In this study, we investigated the capacity of Straumann Bone Ceramic coated with Straumann Emdogain, a clinical preparation of enamel matrix protein (EMP), to aid in hard tissue formation by post-natal mesenchymal stromal cells (MSCs) including bone marrow stromal cells (BMSCs) and periodontal ligament fibroblasts (PDLFs). MSCs were isolated and ex vivo-expanded from human bone marrow and periodontal ligament and, in culture, allowed to attach to Bone Ceramic in the presence or absence of Emdogain. Gene expression of bone-related proteins was investigated by real time RT-PCR for 72 h, and ectopic bone formation was assessed histologically in subcutaneous implants of Bone Ceramic containing MSCs with or without Emdogain in NOD/SCID mice. Alkaline phosphatase activity was also assessed in vitro, in the presence or absence of Emdogain. Collagen-I mRNA was up-regulated in both MSC populations over the 72-h time course with Emdogain. Expression of BMP-2 and the osteogenic transcription factor Cbfa-1 showed early stimulation in both MSC types after 24 h. In contrast, expression of BMP-4 was consistently down-regulated in both MSC types with Emdogain. Up-regulation of osteopontin and periostin mRNA was restricted to BMSCs, while higher levels of bone sialoprotein-II were observed in PDLFs with Emdogain. Furthermore, alkaline phosphatase activity levels were reduced in both BMSCs and PDLFs in the presence of Emdogain. Very little evidence was found for ectopic bone formation following subcutaneous implantation of MSCs with Emdogain-coated or -uncoated Bone Ceramic in NOD/SCID mice. The early up-regulation of several important bone-related genes suggests that Emdogain may have a significant stimulatory effect in the commitment of mesenchymal cells to osteogenic differentiation in vitro. While Emdogain inhibited AP activity and appeared

  10. Human bone marrow and adipose tissue mesenchymal stem cells: a user's guide.

    Science.gov (United States)

    Mosna, Federico; Sensebé, Luc; Krampera, Mauro

    2010-10-01

    Mesenchymal stem cells (MSCs) are adult stem cells that hold great promise in the field of regenerative medicine. They can be isolated from almost any tissue of the body and display, after expansion, very similar properties and minor differences, probably due to their microenvironment of origin. Expansion in vitro can be obtained in cytokine-free, serum-enriched media, as well as in serum-free, basic fibroblast growth factor-enriched media. A detailed immunophenotypic analysis is required to test the purity of the preparation, but no unique distinguishing marker has been described as yet. Functional assays, that is, differentiation studies in vitro, are needed to prove multilineage differentiation of expanded cells, and demonstration of pluripotency is necessary to identify most immature precursors. MSCs show powerful immunomodulative properties toward most of the cells of the immune system: this strengthens the theoretical rationale for their use also in an allogeneic setting across the major histocompatibility complex (MHC) immunological barriers. Systemic intravenous injection and local use have been tried: after systemic injection, MSCs show a high degree of chemotaxis based on pro-inflammatory cytokines, and localize at inflamed and neoplastic tissues; local regeneration has been improved using synthetic, as well as organic scaffolds. On the other hand, inadequate heterotopic in vivo differentiation and neoplastic transformation are potential risks of this form of cell therapy, even if evidence of this sort has been collected only from studies in mice, and generally after prolonged in vitro expansion. This review tries to provide a detailed technical overview of the methods used for human bone-marrow (BM)-derived and adipose-tissue (AT)-derived MSC isolation, in vitro expansion, and characterization for tissue repair. We chose to use BM-MSCs as a model to describe techniques that have been used for MSC isolation and expansion from very different sources, and

  11. CKbeta-8 [CCL23], a novel CC chemokine, is chemotactic for human osteoclast precursors and is expressed in bone tissues.

    Science.gov (United States)

    Votta, B J; White, J R; Dodds, R A; James, I E; Connor, J R; Lee-Rykaczewski, E; Eichman, C F; Kumar, S; Lark, M W; Gowen, M

    2000-05-01

    We have previously demonstrated that a tartrate-resistant acid phosphatase (TRAP)-positive subpopulation of mononuclear cells isolated from collagenase digests of human osteoclastoma tissue exhibits an osteoclast phenotype and can be induced to resorb bone. Using these osteoclast precursors as a model system, we have assessed the chemotactic potential of 16 chemokines. Three CC chemokines, the recently described CKbeta-8, RANTES, and MIP-1alpha elicited significant chemotactic responses. In contrast, 10 other CC chemokines (MIP-1beta, MCP-1, MCP-2, MCP-3, MCP-4, HCC-1, eotaxin-2, PARC, SLC, ELC) and 3 CXC chemokines (IL-8, GROalpha, SDF-1) were inactive. None of these chemokines showed any chemotactic activity for either primary osteoblasts derived from human bone explants or the osteoblastic MG-63 cell line. The identity of the osteoclast receptor that mediates the chemotactic response remains to be established. However, all three active chemokines have been reported to bind to CCR1 and cross-desensitization studies demonstrate that RANTES and MIP-1alpha can partially inhibit the chemotactic response elicited by CKbeta-8. CKbeta-8, the most potent of the active CC chemokines (EC(max) 0.1-0.3 nM), was further characterized with regard to expression in human bone and cartilage. Although expression is not restricted to these tissues, CKbeta-8 mRNA was shown to be highly expressed in osteoblasts and chondrocytes in human fetal bone by in situ hybridization. In addition, CKbeta-8 protein was shown to be present in human osteophytic tissue by immunolocalization. These observations suggest that CKbeta-8, and perhaps other chemokines, may play a role in the recruitment of osteoclast precursors to sites of bone resorption.

  12. Development of Collagen/Demineralized Bone Powder Scaffolds and Periosteum-Derived Cells for Bone Tissue Engineering Application

    Directory of Open Access Journals (Sweden)

    Wilairat Leeanansaksiri

    2013-01-01

    Full Text Available The aim of this study was to investigate physical and biological properties of collagen (COL and demineralized bone powder (DBP scaffolds for bone tissue engineering. DBP was prepared and divided into three groups, based on various particle sizes: 75–125 µm, 125–250 µm, and 250–500 µm. DBP was homogeneously mixed with type I collagen and three-dimensional scaffolds were constructed, applying chemical crosslinking and lyophilization. Upon culture with human periosteum-derived cells (PD cells, osteogenic differentiation of PD cells was investigated using alkaline phosphatase (ALP activity and calcium assay kits. The physical properties of the COL/DBP scaffolds were obviously different from COL scaffolds, irrespective of the size of DBP. In addition, PD cells cultured with COL scaffolds showed significantly higher cell adhesion and proliferation than those with COL/DBP scaffolds. In contrast, COL/DBP scaffolds exhibited greater osteoinductive potential than COL scaffolds. The PD cells with COL/DBP scaffolds possessed higher ALP activity than those with COL scaffolds. PD cells cultured with COL/DBP scaffolds with 250–500 mm particle size yielded the maximum calcium deposition. In conclusion, PD cells cultured on the scaffolds could exhibit osteoinductive potential. The composite scaffold of COL/DBP with 250–500 mm particle size could be considered a potential bone tissue engineering implant.

  13. Comparison of the relationship between bone marrow adipose tissue and volumetric bone mineral density in children and adults.

    Science.gov (United States)

    Shen, Wei; Velasquez, Gilbert; Chen, Jun; Jin, Ye; Heymsfield, Steven B; Gallagher, Dympna; Pi-Sunyer, F Xavier

    2014-01-01

    Several large-scale studies have reported the presence of an inverse relationship between bone mineral density (BMD) and bone marrow adipose tissue (BMAT) in adults. We aim to determine if there is an inverse relationship between pelvic volumetric BMD (vBMD) and pelvic BMAT in children and to compare this relationship in children and adults. Pelvic BMAT and bone volume (BV) was evaluated in 181 healthy children (5-17yr) and 495 healthy adults (≥18yr) with whole-body magnetic resonance imaging (MRI). Pelvic vBMD was calculated using whole-body dual-energy X-ray absorptiometry to measure pelvic bone mineral content and MRI-measured BV. An inverse correlation was found between pelvic BMAT and pelvic vBMD in both children (r=-0.374, pBMAT as the independent variable, being a child or adult neither significantly contribute to the pelvic BMD (p=0.995) nor did its interaction with pelvic BMAT (p=0.415). The inverse relationship observed between pelvic vBMD and pelvic BMAT in children extends previous findings that found the inverse relationship to exist in adults and provides further support for a reciprocal relationship between adipocytes and osteoblasts.

  14. Fabrication and characterization of strontium incorporated 3-D bioactive glass scaffolds for bone tissue from biosilica.

    Science.gov (United States)

    Özarslan, Ali Can; Yücel, Sevil

    2016-11-01

    Bioactive glass scaffolds that contain silica are high viable biomaterials as bone supporters for bone tissue engineering due to their bioactive behaviour in simulated body fluid (SBF). In the human body, these materials help inorganic bone structure formation due to a combination of the particular ratio of elements such as silicon (Si), calcium (Ca), sodium (Na) and phosphorus (P), and the doping of strontium (Sr) into the scaffold structure increases their bioactive behaviour. In this study, bioactive glass scaffolds were produced by using rice hull ash (RHA) silica and commercial silica based bioactive glasses. The structural properties of scaffolds such as pore size, porosity and also the bioactive behaviour were investigated. The results showed that undoped and Sr-doped RHA silica-based bioactive glass scaffolds have better bioactivity than that of commercial silica based bioactive glass scaffolds. Moreover, undoped and Sr-doped RHA silica-based bioactive glass scaffolds will be able to be used instead of undoped and Sr-doped commercial silica based bioactive glass scaffolds for bone regeneration applications. Scaffolds that are produced from undoped or Sr-doped RHA silica have high potential to form new bone for bone defects in tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Microfibril orientation dominates the microelastic properties of human bone tissue at the lamellar length scale.

    Directory of Open Access Journals (Sweden)

    Mathilde Granke

    Full Text Available The elastic properties of bone tissue determine the biomechanical behavior of bone at the organ level. It is now widely accepted that the nanoscale structure of bone plays an important role to determine the elastic properties at the tissue level. Hence, in addition to the mineral density, the structure and organization of the mineral nanoparticles and of the collagen microfibrils appear as potential key factors governing the elasticity. Many studies exist on the role of the organization of collagen microfibril and mineral nanocrystals in strongly remodeled bone. However, there is no direct experimental proof to support the theoretical calculations. Here, we provide such evidence through a novel approach combining several high resolution imaging techniques: scanning acoustic microscopy, quantitative scanning small-Angle X-ray scattering imaging and synchrotron radiation computed microtomography. We find that the periodic modulations of elasticity across osteonal bone are essentially determined by the orientation of the mineral nanoparticles and to a lesser extent only by the particle size and density. Based on the strong correlation between the orientation of the mineral nanoparticles and the collagen molecules, we conclude that the microfibril orientation is the main determinant of the observed undulations of microelastic properties in regions of constant mineralization in osteonal lamellar bone. This multimodal approach could be applied to a much broader range of fibrous biological materials for the purpose of biomimetic technologies.

  16. Interactions between inorganic and organic phases in bone tissue as a source of inspiration for design of novel nanocomposites

    NARCIS (Netherlands)

    Farbod, K.; Nejadnik, M.R.; Jansen, J.A.; Leeuwenburgh, S.C.G.

    2014-01-01

    Mimicking the nanostructure of bone and understanding the interactions between the nanoscale inorganic and organic components of the extracellular bone matrix are crucial for the design of biomaterials with structural properties and a functionality similar to the natural bone tissue. Generally, thes

  17. Development of bioactive porous α-TCP/HAp beads for bone tissue engineering.

    Science.gov (United States)

    Asaoka, Teruo; Ohtake, Shoji; Furukawa, Katsuko S; Tamura, Akito; Ushida, Takashi

    2013-11-01

    Porous beads of bioactive ceramics such as hydroxyapatite (HAp) and tribasic calcium phosphate (TCP) are considered a promising scaffold for cultivating bone cells. To realize this, α-TCP/HAp functionally graded porous beads are fabricated with two main purposes: to maintain the function of the scaffold with sufficient strength up to the growth of new bone, and is absorbed completely after the growth. HAp is a bioactive material that has both high strength and strong tissue-adhesive properties, but is not readily absorbed by the human body. On the contrary, α-TCP is highly bioabsorbable, resulting in a scaffold that is absorbed before it is completely replaced by bone. In this study, we produced porous, bead-shaped carriers as scaffolds for osteoblast culture. To control the solubility in vivo, the fabricated beads contained α-TCP at the center and HAp at the surface. Cell adaptability of these beads for bone tissue engineering was confirmed in vitro. It was found that α-TCP/HAp bead carriers exhibit low toxicity in the initial stages of cell seeding and cell adhesion. The presence of HAp in the composite bead form effectively increased ALP activity. In conclusion, it is suggested that these newly developed α-TCP/HAp beads are a promising tool for bone tissue engineering.

  18. Prediction of Local Ultimate Strain and Toughness of Trabecular Bone Tissue by Raman Material Composition Analysis

    Directory of Open Access Journals (Sweden)

    Roberto Carretta

    2015-01-01

    Full Text Available Clinical studies indicate that bone mineral density correlates with fracture risk at the population level but does not correlate with individual fracture risk well. Current research aims to better understand the failure mechanism of bone and to identify key determinants of bone quality, thus improving fracture risk prediction. To get a better understanding of bone strength, it is important to analyze tissue-level properties not influenced by macro- or microarchitectural factors. The aim of this pilot study was to identify whether and to what extent material properties are correlated with mechanical properties at the tissue level. The influence of macro- or microarchitectural factors was excluded by testing individual trabeculae. Previously reported data of mechanical parameters measured in single trabeculae under tension and bending and its compositional properties measured by Raman spectroscopy was evaluated. Linear and multivariate regressions show that bone matrix quality but not quantity was significantly and independently correlated with the tissue-level ultimate strain and postyield work (r=0.65–0.94. Principal component analysis extracted three independent components explaining 86% of the total variance, representing elastic, yield, and ultimate components according to the included mechanical parameters. Some matrix parameters were both included in the ultimate component, indicating that the variation in ultimate strain and postyield work could be largely explained by Raman-derived compositional parameters.

  19. EFFECTS OF HYALURONAN ON THREE-DIMENSIONAL MICROARCHITECTURE OF SUBCHONDRAL BONE TISSUES IN GUINEA PIG PRIMARY OSTEOARTHROSIS

    DEFF Research Database (Denmark)

    Ding, Ming

    Introduction: It is not known whether hyaluronan (HA) has any effect on the underlying subchondral bone tissues. This study was to investigate the effects of high molecular weight HA (1.5x106 Daltons) intra-articular injection on subchondral bone tissues. Methods: Fifty-six male guinea pigs (6......-term study, these latter changes were more pronounced, with an additionally significant decrease in connectivity and bone surface density. HA groups had greater bone mineral concentration and mineral density, lower collagen to mineral ratio, and preserved the mechanical properties of cancellous bone....... The effects of HA on cartilage and subchondral bone were maintained when HA treatment was discontinued. Discussion: Significant positive effects of high molecular weight HA on the articular cartilage and subchondral bone tissues were seen. HA protects against OA-related cartilage degradation to almost normal...

  20. Prevalence, extension and characteristics of fluid-fluid levels in bone and soft tissue tumors

    Energy Technology Data Exchange (ETDEWEB)

    Dyck, P. van; Venstermans, C.; Gielen, J.; Parizel, P.M. [University Hospital Antwerp, Department of Radiology, Edegem (Belgium); Vanhoenacker, F.M. [University Hospital Antwerp, Department of Radiology, Edegem (Belgium); AZ St-Maarten, Department of Radiology, Duffel/Mechelen (Belgium); Vogel, J. [Leiden University Medical Centre, Department of Orthopedics, Leiden (Netherlands); Kroon, H.M.; Bloem, J.L. [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Schepper, A.M.A. de [University Hospital Antwerp, Department of Radiology, Edegem (Belgium); Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands)

    2006-12-15

    The purpose of this study was to determine the prevalence, extension and signal characteristics of fluid-fluid levels in a large series of 700 bone and 700 soft tissue tumors. Out of a multi-institutional database, MRI of 700 consecutive patients with a bone tumor and MRI of 700 consecutive patients with a soft tissue neoplasm were retrospectively reviewed for the presence of fluid-fluid levels. Extension (single, multiple and proportion of the lesion occupied by fluid-fluid levels) and signal characteristics on magnetic resonance imaging of fluid-fluid levels were determined. In all patients, pathologic correlation was available. Of 700 patients with a bone tumor, 19 (10 male and 9 female; mean age, 29 years) presented with a fluid-fluid level (prevalence 2.7%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included aneurysmal bone cyst (ten cases), fibrous dysplasia (two cases), osteoblastoma (one case), simple bone cyst (one case), telangiectatic osteosarcoma (one case), ''brown tumor'' (one case), chondroblastoma (one case) and giant cell tumor (two cases). Of 700 patients with a soft tissue tumor, 20 (9 males and 11 females; mean age, 34 years) presented with a fluid-fluid level (prevalence 2.9%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included cavernous hemangioma (12 cases), synovial sarcoma (3 cases), angiosarcoma (1 case), aneurysmal bone cyst of soft tissue (1 case), myxofibrosarcoma (1 case) and high-grade sarcoma ''not otherwise specified'' (2 cases). In our series, the largest reported in the literature to the best of our knowledge, the presence of fluid-fluid levels is a rare finding with a prevalence of 2.7 and 2.9% in bone and soft tissue tumors, respectively. Fluid-fluid levels remain a non-specific finding and can