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Sample records for bone tissue structure

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

    PubMed

    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.

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

    PubMed Central

    Florencio-Silva, Rinaldo; 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. PMID:26247020

  3. Composites structures for bone tissue reconstruction

    SciTech Connect

    Neto, W.; Santos, João; Avérous, L.; Schlatter, G.; Bretas, Rosario

    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.

  4. Composites structures for bone tissue reconstruction

    NASA Astrophysics Data System (ADS)

    Neto, W.; Santos, João.; Avérous, L.; Schlatter, G.; Bretas, Rosario.

    2015-05-01

    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.

  5. Structural Assessment of a Tissue Engineered Scaffold for Bone Repair

    DTIC Science & Technology

    2001-10-25

    lactide-co- glycolide) [ PLAGA ] have been evaluated for such uses. However, structural limitations may restrict the clinical use of these scaffolds...bone specific protein. Through this work, it was shown that an osteoconductive PLAGA scaffold with a pore system equivalent to the structure of...known as poly(lactide-co-glycolide) [ PLAGA ]. Our laboratory has conducted several studies evaluating the ability of PLAGA to promote osteoblast

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

    PubMed

    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.

  7. Structural bone allograft combined with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering.

    PubMed

    Xie, Chao; Reynolds, David; Awad, Hani; Rubery, Paul T; Pelled, Gadi; Gazit, Dan; Guldberg, Robert E; Schwarz, Edward M; O'Keefe, Regis J; Zhang, Xinping

    2007-03-01

    The presence of live periosteal progenitor cells on the surface of bone autografts confers better healing than devitalized allograft. We have previously demonstrated in a murine 4 mm segmental femoral bone-grafting model that live periosteum produces robust endochondral and intramembraneous bone formation that is essential for effective healing and neovascularization of structural bone grafts. To the end of engineering a live pseudo-periosteum that could induce a similar response onto devitalized bone allograft, we seeded a mesenchymal stem cell line stably transfected with human bone morphogenic protein-2/beta-galactosidase (C9) onto devitalized bone allografts or onto a membranous small intestinal submucosa scaffold that was wrapped around the allograft. Histology showed that C9-coated allografts displayed early cartilaginous tissue formation at day 7. By 6 and 9 weeks, a new cortical shell was found bridging the segmental defect that united the host bones. Biomechanical testing showed that C9-coated allografts displayed torsional strength and stiffness equivalent to intact femurs at 6 weeks and superior to live isografts at 9 weeks. Volumetric and histomorphometric micro-computed tomography analyses demonstrated a 2-fold increase in new bone formation around C9-coated allografts, which resulted in a substantial increase in polar moment of inertia (pMOI) due to the formation of new cortical shell around the allografts. Positive correlations between biomechanics and new bone volume and pMOI were found, suggesting that the biomechanical function of the grafted femur relates to both morphological parameters. C9-coated allograft also exhibited slower resorption of the graft cortex at 9 weeks than live isograft. Both new bone formation and the persistent allograft likely contributed to the improved biomechanics of C9-coated allograft. Taken together, we propose a novel strategy to combine structural bone allograft with genetically engineered mesenchymal stem cells as

  8. Is there any information on micro-structure in microwave tomography of bone tissue?

    PubMed

    Irastorza, R M; Carlevaro, C M; Vericat, F

    2013-08-01

    In this work, two-dimensional simulations of the microwave dielectric properties of models with ellipses and realistic models of trabecular bone tissue are performed. In these simulations, finite difference time domain methodology has been applied to simulate two-phase structures containing inclusions. The results presented here show that the micro-structure is an important factor in the effective dielectric properties of trabecular bone. We consider the feasibility of using the dielectric behaviour of bone tissue to be an indicator of bone health. The frequency used was 950 MHz. It was found that the dielectric properties can be used as an estimate of the degree of anisotropy of the micro-structure of the trabecular tissue. Conductivity appears to be the most sensitive parameter in this respect. Models with ellipse shaped-inclusions are also tested to study their application to modelling bone tissue. Models with ellipses that had an aspect ratio of a/b=1.5 showed relatively good agreement when compared with realistic models of bone tissue. According to the results presented here, the anisotropy of trabecular bone must be accounted for when measuring its dielectric properties using microwave imaging.

  9. [Normal tissue tolerance to external beam radiation therapy: Bone marrow and cortical bone structures].

    PubMed

    Schernberg, A; Hennequin, C

    2017-10-01

    In patients undergoing external radiation therapy, bone marrow and cortical bone structures are all often neglected as organs at risk. Still, from increased febrile neutropenia risk in patients undergoing chemoradiation for a pelvic tumour to increased risk of vertebral fracture when undergoing hypofractioned stereotactic radiotherapy of a spinal metastasis, adverse effects are frequent and sometimes serious. This literature review first defines the rules for contouring these structures, then the dose constraints currently recommended. This article focuses first on conventional irradiation or intensity modulation radiotherapy considering classical fractionation. Secondly, it focuses on stereotactic radiotherapy. The considered organs will be haematopoietic structures, and bone cortical structures. Current recommendations are summarised in a table. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  10. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering.

    PubMed

    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.

  11. Contribution of mineral to bone structural behavior and tissue mechanical properties.

    PubMed

    Donnelly, Eve; Chen, Dan X; Boskey, Adele L; Baker, Shefford P; van der Meulen, Marjolein C H

    2010-11-01

    Bone geometry and tissue material properties jointly govern whole-bone structural behavior. While the role of geometry in structural behavior is well characterized, the contribution of the tissue material properties is less clear, partially due to the multiple tissue constituents and hierarchical levels at which these properties can be characterized. Our objective was to elucidate the contribution of the mineral phase to bone mechanical properties across multiple length scales, from the tissue material level to the structural level. Vitamin D and calcium deficiency in 6-week-old male rats was employed as a model of reduced mineral content with minimal collagen changes. The structural properties of the humeri were measured in three-point bending and related to the mineral content and geometry from microcomputed tomography. Whole-cortex and local bone tissue properties were examined with infrared (IR) spectroscopy, Raman spectroscopy, and nanoindentation to understand the role of altered mineral content on the constituent material behavior. Structural stiffness (-47%) and strength (-50%) were reduced in vitamin D-deficient (-D) humeri relative to controls. Moment of inertia (-38%), tissue mineral density (TMD, -9%), periosteal mineralization (-28%), and IR mineral:matrix ratio (-19%) were reduced in -D cortices. Thus, both decreased tissue mineral content and changes in cortical geometry contributed to impaired skeletal load-bearing function. In fact, 97% of the variability in humeral strength was explained by moment of inertia, TMD, and IR mineral:matrix ratio. The strong relationships between structural properties and cortical material composition demonstrate a critical role of the microscale material behavior in skeletal load-bearing performance.

  12. Contribution of mineral to bone structural behavior and tissue mechanical properties

    PubMed Central

    Donnelly, Eve; Chen, Dan X.; Boskey, Adele L.; Baker, Shefford P.; Meulen, Marjolein C. H. van der

    2010-01-01

    Bone geometry and tissue material properties jointly govern whole-bone structural behavior. While the role of geometry in structural behavior is well characterized, the contribution of the tissue material properties is less clear, partially due to the multiple tissue constituents and hierarchical levels at which these properties can be characterized. Our objective was to elucidate the contribution of the mineral phase to bone mechanical properties across multiple length scales, from the tissue material level to the structural level. Vitamin D and calcium deficiency in 6-week-old male rats was employed as a model of reduced mineral content with minimal collagen changes. The structural properties of the humeri were measured in three-point bending and related to the mineral content and geometry from microcomputed tomography. Whole-cortex and local bone tissue properties were examined with infrared (IR) spectroscopy, Raman spectroscopy, and nanoindentation, to understand the role of altered mineral content on the constituent material behavior. Structural stiffness (-47%) and strength (-50%) were reduced in vitamin D-deficient (-D) humeri relative to controls. Moment of inertia (-38%), tissue mineral density (TMD, -9%), periosteal mineralization (-28%), and IR mineral:matrix ratio (-19%) were reduced in -D cortices. Thus, both decreased tissue mineral content and changes in cortical geometry contributed to impaired skeletal load bearing function. In fact, 97% of the variability in humeral strength was explained by moment of inertia, TMD, and IR mineral:matrix ratio. The strong relationships between structural properties and cortical material composition demonstrate a critical role of the microscale material behavior in skeletal load-bearing performance. PMID:20730582

  13. Local electronic structure and nanolevel hierarchical organization of bone tissue: theory and NEXAFS study

    NASA Astrophysics Data System (ADS)

    Pavlychev, A. A.; Avrunin, A. S.; Vinogradov, A. S.; Filatova, E. O.; Doctorov, A. A.; Krivosenko, Yu S.; Samoilenko, D. O.; Svirskiy, G. I.; Konashuk, A. S.; Rostov, D. A.

    2016-12-01

    Theoretical and experimental investigations of native bone are carried out to understand relationships between its hierarchical organization and local electronic and atomic structure of the mineralized phase. The 3D superlattice model of a coplanar assembly of the hydroxyapatite (HAP) nanocrystallites separated by the hydrated nanolayers is introduced to account the interplay of short-, long- and super-range order parameters in bone tissue. The model is applied to (i) predict and rationalize the HAP-to-bone spectral changes in the electronic structure and (ii) describe the mechanisms ensuring the link of the hierarchical organization with the electronic structure of the mineralized phase in bone. To check the predictions the near-edge x-ray absorption fine structure (NEXAFS) at the Ca 2p, P 2p and O 1s thresholds is measured for native bone and compared with NEXAFS for reference compounds. The NEXAFS analysis has demonstrated the essential hierarchy induced HAP-to-bone red shifts of the Ca and P 2p-to-valence transitions. The lowest O 1s excitation line at 532.2 eV in bone is assigned with superposition of core transitions in the hydroxide OH-(H2O) m anions, Ca2+(H2O) n cations, the carboxyl groups inside the collagen and [PO4]2- and [PO4]- anions with unsaturated P-O bonds.

  14. Alendronate treatment alters bone tissues at multiple structural levels in healthy canine cortical bone.

    PubMed

    Acevedo, Claire; Bale, Hrishikesh; Gludovatz, Bernd; Wat, Amy; Tang, Simon Y; Wang, Mingyue; Busse, Björn; Zimmermann, Elizabeth A; Schaible, Eric; Allen, Matthew R; Burr, David B; Ritchie, Robert O

    2015-12-01

    Bisphosphonates are widely used to treat osteoporosis, but have been associated with atypical femoral fractures (AFFs) in the long term, which raises a critical health problem for the aging population. Several clinical studies have suggested that the occurrence of AFFs may be related to the bisphosphonate-induced changes of bone turnover, but large discrepancies in the results of these studies indicate that the salient mechanisms responsible for any loss in fracture resistance are still unclear. Here the role of bisphosphonates is examined in terms of the potential deterioration in fracture resistance resulting from both intrinsic (plasticity) and extrinsic (shielding) toughening mechanisms, which operate over a wide range of length-scales. Specifically, we compare the mechanical properties of two groups of humeri from healthy beagles, one control group comprising eight females (oral doses of saline vehicle, 1 mL/kg/day, 3 years) and one treated group comprising nine females (oral doses of alendronate used to treat osteoporosis, 0.2mg/kg/day, 3 years). Our data demonstrate treatment-specific reorganization of bone tissue identified at multiple length-scales mainly through advanced synchrotron x-ray experiments. We confirm that bisphosphonate treatments can increase non-enzymatic collagen cross-linking at molecular scales, which critically restricts plasticity associated with fibrillar sliding, and hence intrinsic toughening, at nanoscales. We also observe changes in the intracortical architecture of treated bone at microscales, with partial filling of the Haversian canals and reduction of osteon number. We hypothesize that the reduced plasticity associated with BP treatments may induce an increase in microcrack accumulation and growth under cyclic daily loadings, and potentially increase the susceptibility of cortical bone to atypical (fatigue-like) fractures.

  15. Cellulose and collagen derived micro-nano structured scaffolds for bone tissue engineering.

    PubMed

    Aravamudhan, Aja; Ramos, Daisy M; Nip, Jonathan; Harmon, Matthew D; James, Roshan; Deng, Meng; Laurencin, Cato T; Yu, Xiaojun; Kumbar, Sangamesh G

    2013-04-01

    Scaffold based bone tissue engineering (BTE) has made great progress in regenerating lost bone tissue. Materials of natural and synthetic origin have been used for scaffold fabrication. Scaffolds derived from natural polymers offer greater bioactivity and biocompatibility with mammalian tissues to favor tissue healing, due to their similarity to native extracellular matrix (ECM) components. Often it is a challenge to fabricate natural polymer based scaffolds for BTE applications without compromising their bioactivity, while maintaining adequate mechanical properties. In this work, we report the fabrication and characterization of cellulose and collagen based micro-nano structured scaffolds using human osteoblasts (HOB) for BTE applications. These porous micro-nano structured scaffolds (average pore diameter 190 +/- 10 microm) exhibited mechanical properties in the mid range of human trabecular bone (compressive modulus 266.75 +/- 33.22 MPa and strength 12.15 3 +/- 2.23 MPa). These scaffolds supported the greater adhesion and phenotype maintenance of cultured HOB as reflected by higher levels of osteogenic enzyme alkaline phosphatase and mineral deposition compared to control polyester micro-nano structured scaffolds of identical pore properties. These natural polymer based micro-nano structured scaffolds may serve as alternatives to polyester based scaffolds for BTE applications.

  16. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

    PubMed Central

    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. PMID:26604759

  17. [Bone tissue: rebuilding and inflammation].

    PubMed

    Jakab, Lajos

    2014-10-05

    In this review the author summarizes the knowledge related to structural elements of bone tissue. The process of bone reorganisation and knowledge about the special feature of bone metabolism in human are also discussed. It is noted that due to the reorganisation, there is a complete renewal of bone tissue in every 10 years, and this renewal lasts throughout the life. However, there are life periods when osteoclast activity is low, e.g. in childhood and the second decade of life when the gain of bone mass may be as much as 40% of the final bone mass. Overactivity of osteoclasts occurs at age 60 years in men and somewhat earlier in women. Reorganization of bone tissue is an elementary requirement for the physiological functions (locomotion, hemopoiesis, immune functions). The RANK-RANKL-osteoprotegerin axis plays an important role in the regulation of bone metabolism. Bone mass is dependent on osteocytes; osteoblasts are building up while osteoclasts are reabsorbing bone tissue. In this process transcription factors, hormone-like substances and a large number of cytokines are involved. In addition, the inflammatory process within the bone tissue as well as the defending, reparative inflammation and specific immune response are of great importance in bone reorganisation. This is particularly valid for α2-macroglobulin and transforming growth factor, although the exact role in bone reorganization has not been fully explored. It can be concluded that the elements, which participate in bone reorganization and in defending inflammatory and specific immunological processes, are essentially identical. Therefore, the existence of an osteo-immunological complex system has emerged.

  18. Structure and functionalization of mesoporous bioceramics for bone tissue regeneration and local drug delivery.

    PubMed

    Vallet-Regí, María; Izquierdo-Barba, Isabel; Colilla, Montserrat

    2012-03-28

    This review article describes the importance of structure and functionalization in the performance of mesoporous silica bioceramics for bone tissue regeneration and local drug delivery purposes. Herein, we summarize the pivotal features of mesoporous bioactive glasses, also known as 'templated glasses' (TGs), which present chemical compositions similar to those of conventional bioactive sol-gel glasses and the added value of an ordered mesopore arrangement. An in-depth study concerning the possibility of tailoring the structural and textural characteristics of TGs at the nanometric scale and their influence on bioactive behaviour is discussed. The highly ordered mesoporous arrangement of cavities allows these materials to confine drugs to be subsequently released, acting as drug delivery devices. The functionalization of mesoporous silica walls has been revealed as the cornerstone in the performance of these materials as controlled release systems. The synergy between the improved bioactive behaviour and local sustained drug release capability of mesostructured materials makes them suitable to manufacture three-dimensional macroporous scaffolds for bone tissue engineering. Finally, this review tackles the possibility of covalently grafting different osteoinductive agents to the scaffold surface that act as attracting signals for bone cells to promote the bone regeneration process.

  19. Micro-CT-based screening of biomechanical and structural properties of bone tissue engineering scaffolds.

    PubMed

    Van Cleynenbreugel, Tim; Schrooten, Jan; Van Oosterwyck, Hans; Vander Sloten, Jos

    2006-07-01

    The development of successful scaffolds for bone tissue engineering requires a concurrent engineering approach that combines different research fields. In order to limit in vivo experiments and reduce trial and error research, a scaffold screening technique has been developed. In this protocol seven structural and three biomechanical properties of potential scaffold materials are quantified and compared to the desired values. The property assessment is done on computer models of the scaffolds, and these models are based on micro-CT images. As a proof of principle, three porous scaffolds were evaluated with this protocol: stainless steel, hydroxyapatite, and titanium. These examples demonstrate that the modelling technique is able to quantify important scaffold properties. Thus, a powerful technique for automated screening of bone tissue engineering scaffolds has been developed that in a later stage may be used to tailor the scaffold properties to specific requirements.

  20. [Effect of peptide regulators on the structural and functional status of bone tissue in ageing rats].

    PubMed

    Povorozniuk, V V; Khavinson, V Kh; Makogonchuk, A V; Ryzhak, G A; Kreslov, E A; Gopkalova, I V

    2007-01-01

    The wide spread of osteoporosis in women in the post-menopausal period stipulates the need for new effective means of prevention and correction of pathologic alterations in the bone tissue. Effect of two peptide bioregulators: cartilages preparation based on the cartilaginous tissue extract and T-31 substance on the mineral density of rat bone tissue has been studied in the experimental model of osteoporosis. The study has revealed an osteoprotective effect of both studied substances, with significantly higher efficacy of the preparation based on cartilaginous tissue extract. The substances exerted both prophylactic effect on the status of the cartilaginous tissue, preventing the decrease of mineral density of the bone tissue in rats after ovariectomy, and corrective effect by increasing the bone tissue density, which was reduced as a result of ovariectomy.

  1. Effects of osteoporosis and nutrition supplements on structures and nanomechanical properties of bone tissue.

    PubMed

    Chang, Yuan-Ting; Chen, Chuan-Mu; Tu, Min-Yu; Chen, Hsiao-Ling; Chang, Shou-Yi; Tsai, Tung-Chou; Wang, Ying-Ting; Hsiao, Hsiang-Long

    2011-10-01

    In this study, the bone structures, nanomechanical properties and fracture behaviors in different groups of female C57BL/6 mice (control, sham operated, ovariectomized, casein supplemented, and fermented milk supplemented) were examined by micro-computed tomography, scanning and transmission electron microscopy, and nanoindentation. The control and sham operated mice showed dense bone structures with high cortical bone mineral densities of 544 mg/cm(3) (average) and high hardness of 0.9-1.1 GPa; resistance to bone fracture was conferred by microcracking, crack deflections and ligament bridging attributed to aligned collagen fibers and densely packed hydroxyapatite crystals. Bone mineral density, hardness and fracture resistance in ovariectomized mice markedly dropped due to loose bone structure with randomly distributed collagens and hydroxyapatites. The acidic casein supplemented mice with blood acidosis exhibited poor mineral absorption and loose bone structure, whereas the neutralized casein or fermented milk supplemented mice were resistant to osteoporosis and had high bone mechanical properties.

  2. Craniofacial bone tissue engineering.

    PubMed

    Wan, Derrick C; Nacamuli, Randall P; Longaker, Michael T

    2006-04-01

    Repair and reconstruction of the craniofacial skeleton represents a significant biomedical burden, with thousands of procedures per-formed annually secondary to injuries and congenital malformations. Given the multitude of current approaches, the need for more effective strategies to repair these bone deficits is apparent. This article explores two major modalities for craniofacial bone tissue engineering: distraction osteogenesis and cellular based therapies. Current understanding of the guiding principles for each of these modalities is elaborated on along with the knowledge gained from clinical and investigative studies. By laying this foundation, future directions for craniofacial distraction and cell-based bone engineering have emerged with great promise for the advancement of clinical practice.

  3. Testing the Hypothesis of Biofilm as a Source for Soft Tissue and Cell-Like Structures Preserved in Dinosaur Bone

    PubMed Central

    2016-01-01

    Recovery of still-soft tissue structures, including blood vessels and osteocytes, from dinosaur bone after demineralization was reported in 2005 and in subsequent publications. Despite multiple lines of evidence supporting an endogenous source, it was proposed that these structures arose from contamination from biofilm-forming organisms. To test the hypothesis that soft tissue structures result from microbial invasion of the fossil bone, we used two different biofilm-forming microorganisms to inoculate modern bone fragments from which organic components had been removed. We show fundamental morphological, chemical and textural differences between the resultant biofilm structures and those derived from dinosaur bone. The data do not support the hypothesis that biofilm-forming microorganisms are the source of these structures. PMID:26926069

  4. Testing the Hypothesis of Biofilm as a Source for Soft Tissue and Cell-Like Structures Preserved in Dinosaur Bone.

    PubMed

    Schweitzer, Mary Higby; Moyer, Alison E; Zheng, Wenxia

    2016-01-01

    Recovery of still-soft tissue structures, including blood vessels and osteocytes, from dinosaur bone after demineralization was reported in 2005 and in subsequent publications. Despite multiple lines of evidence supporting an endogenous source, it was proposed that these structures arose from contamination from biofilm-forming organisms. To test the hypothesis that soft tissue structures result from microbial invasion of the fossil bone, we used two different biofilm-forming microorganisms to inoculate modern bone fragments from which organic components had been removed. We show fundamental morphological, chemical and textural differences between the resultant biofilm structures and those derived from dinosaur bone. The data do not support the hypothesis that biofilm-forming microorganisms are the source of these structures.

  5. [State of the microscopic and crystalline structures, the microhardness and mineral saturation of human bone tissue after prolonged space flight].

    PubMed

    Gazenko, O G; Prokhonchukov, A A; Panikarovskiĭ, V V; Tigranian, R A; Kolesnik, A G

    1977-01-01

    The bone tissue removed by autopsy from the crewmembers of the orbital station Salyut-1 after their 23-day space flight was investigated histologically, crystallographically, biophysically and biochemically. The comprehensive studies showed good correlation of the parameters studied. The microscopic and crystalline structures of bone tissue of every skeletal bone tested (ox calcis, frmoral epiphysis and diaphysis, vertebrae, ribs, sternum) did not differ from the normal. The data were in agreement with the parameters of bone microhardness and mineralization which also remained within the normal limits. No pathological changes in the above parameters were noted. Greater packing of the crystal lattice, increased microhardness and mineralization of bone tissue can be attributed to the effect of exercises.

  6. Instrumental methods and techniques for structural and physicochemical characterization of biomaterials and bone tissue: A review.

    PubMed

    Mitić, Žarko; Stolić, Aleksandra; Stojanović, Sanja; Najman, Stevo; Ignjatović, Nenad; Nikolić, Goran; Trajanović, Miroslav

    2017-10-01

    A review of recent advances in instrumental methods and techniques for structural and physicochemical characterization of biomaterials and bone tissue is presented in this paper. In recent years, biomaterials attracted great attention primarily because of the wide range of biomedical applications. This paper focuses on the practical aspects of instrumental methods and techniques that were most often applied (X-ray methods, vibrational spectroscopy (IR and Raman), magnetic-resonance spectroscopy (NMR and ESR), mass spectrometry (MS), atomic absorption spectrometry (AAS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES), thermogravimetry (TG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM)) in the structural investigation and physicochemical characterization of biomaterials and bone tissue. The application of some other physicochemical methods was also discussed. Hands-on information is provided about these valuable research tools, emphasizing practical aspects such as typical measurement conditions, their limitations and advantages, interpretation of results and practical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Collagen for bone tissue regeneration.

    PubMed

    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.

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

    PubMed

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

    2015-09-01

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

  9. Structural and material approaches to bone tissue engineering in powder-based three-dimensional printing.

    PubMed

    Butscher, A; Bohner, M; Hofmann, S; Gauckler, L; Müller, R

    2011-03-01

    This article reviews the current state of knowledge concerning the use of powder-based three-dimensional printing (3DP) for the synthesis of bone tissue engineering scaffolds. 3DP is a solid free-form fabrication (SFF) technique building up complex open porous 3D structures layer by layer (a bottom-up approach). In contrast to traditional fabrication techniques generally subtracting material step by step (a top-down approach), SFF approaches allow nearly unlimited designs and a large variety of materials to be used for scaffold engineering. Today's state of the art materials, as well as the mechanical and structural requirements for bone scaffolds, are summarized and discussed in relation to the technical feasibility of their use in 3DP. Advances in the field of 3DP are presented and compared with other SFF methods. Existing strategies on material and design control of scaffolds are reviewed. Finally, the possibilities and limiting factors are addressed and potential strategies to improve 3DP for scaffold engineering are proposed.

  10. Bone-tissue engineering: complex tunable structural and biological responses to injury, drug delivery, and cell-based therapies.

    PubMed

    Alghazali, Karrer M; Nima, Zeid A; Hamzah, Rabab N; Dhar, Madhu S; Anderson, David E; Biris, Alexandru S

    2015-01-01

    Bone loss and failure of proper bone healing continues to be a significant medical condition in need of solutions that can be implemented successfully both in human and veterinary medicine. This is particularly true when large segmental defects are present, the bone has failed to return to normal form or function, or the healing process is extremely prolonged. Given the inherent complexity of bone tissue - its unique structural, mechanical, and compositional properties, as well as its ability to support various cells - it is difficult to find ideal candidate materials that could be used as the foundation for tissue regeneration from technological platforms. Recently, important developments have been made in the implementation of complex structures built both at the macro- and the nano-level that have been shown to positively impact bone formation and to have the ability to deliver active biological molecules (drugs, growth factors, proteins, cells) for controlled tissue regeneration and the prevention of infection. These materials are diverse, ranging from polymers to ceramics and various composites. This review presents developments in this area with a focus on the role of scaffold structure and chemistry on the biologic processes that influence bone physiology and regeneration.

  11. Hierarchical Structure of Articular Bone-Cartilage Interface and Its Potential Application for Osteochondral Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Bian, Weiguo; Qin, Lian; Li, Dichen; Wang, Jin; Jin, Zhongmin

    2010-09-01

    The artificial biodegradable osteochondral construct is one of mostly promising lifetime substitute in the joint replacement. And the complex hierarchical structure of natural joint is important in developing the osteochondral construct. However, the architecture features of the interface between cartilage and bone, in particular those at the micro-and nano-structural level, remain poorly understood. This paper investigates these structural data of the cartilage-bone interface by micro computerized tomography (μCT) and Scanning Electron Microscope (SEM). The result of μCT shows that important bone parameters and the density of articular cartilage are all related to the position in the hierarchical structure. The conjunctions of bone and cartilage were defined by SEM. All of the study results would be useful for the design of osteochondral construct further manufactured by nano-tech. A three-dimensional model with gradient porous structure is constructed in the environment of Pro/ENGINEERING software.

  12. [Osteostimulating effect of bone xenograft on bone tissue regeneration].

    PubMed

    Balin, V N; Balin, D V; Iordanishvili, A K; Musikin, M I

    2015-01-01

    The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.

  13. Bone Tissue Engineering: Recent Advances and Challenges

    PubMed Central

    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

  14. Bone tissue engineering: recent advances and challenges.

    PubMed

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

    2012-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2017-06-01

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

  16. Optimization of the structure of polyurethanes for bone tissue engineering applications.

    PubMed

    Bil, Monika; Ryszkowska, Joanna; Woźniak, Piotr; Kurzydłowski, Krzysztof J; Lewandowska-Szumieł, Małgorzata

    2010-07-01

    Polyurethanes containing 22-70 wt.% hard segments were developed and evaluated for bone tissue engineering applications. Aliphatic poly(ester-urethanes) were synthesised from poly(epsilon-caprolactone) diol with different molecular masses (M= approximately 530, 1250 and 2000 Da), cycloaliphatic diisocyanate 4,4'-methylenebis(cyclohexyl isocyanate) and ethylene glycol as a chain extender. Changes in macromolecule order with increasing hard segment content were observed via modulated differential scanning calorimetry. Depending on the hard segment content, a gradual variation in polyurethane surface properties was revealed by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and static contact angle measurements. As the hard segments content increased the polyurethane surface exhibited more phase separation, a higher content of urethane moieties and higher hydrophilicity. The biocompatibility results indicated that proliferation of human bone-derived cells (HBDC) cultured in vitro improved with increasing hard segment content while the osteogenic potential of HBDC decreased with increasing hard segment content.

  17. Fabrication and Characterization of Biomimetic Collagen-Apatite Scaffolds with Tunable Structures for Bone Tissue Engineering

    PubMed Central

    Xia, Zengmin; Yu, Xiaohua; Jiang, Xi; Brody, Harold D; Rowe, David W; Wei, Mei

    2013-01-01

    The objective of the current study is to prepare a biomimetic collagen-apatite (Col-Ap) scaffold for improved bone repair and regeneration. A novel bottom-up approach has been developed, which combines a biomimetic self-assembly method with a controllable freeze casting technology. In this study, the mineralized collagen fibers were generated using a simple one-step co-precipitation method which involved collagen self-assembly and in situ apatite precipitation in a collagen-containing modified simulated body fluid (m-SBF). The precipitates were subjected to controllable freeze casting, forming scaffolds with either an isotropic equiaxed structure or a unidirectional lamellar structure. These scaffolds were comprised of collagen fibers and poorly crystalline bone-like carbonated apatite nanoparticles. The mineral content in the scaffold could be tailored in a range 0–54 wt% by simply adjusting the collagen content in the m-SBF. Further, the mechanisms of the formation of both the equiaxed and the lamellar scaffolds were investigated, and freezing regimes for equiaxed and lamellar solidification were established. Finally, bone forming capability of such prepared scaffolds was evaluated in vivo in a mouse calvarial defect model. It was confirmed that the scaffolds well support new bone formation. PMID:23567944

  18. A Biomimetic Collagen-Apatite Scaffold with a Multi-Level Lamellar Structure for Bone Tissue Engineering

    PubMed Central

    Xia, Z.; Villa, M. M.; Wei, M.

    2014-01-01

    Collagen-apatite (Col-Ap) scaffolds have been widely employed for bone tissue engineering. We fabricated a Col-Ap scaffold with a unique multi-level lamellar structure consisting of co-aligned micro and macro pores. The basic building blocks of this scaffold are bone-like mineralized collagen fibers developed via a biomimetic self-assembly process in a collagen-containing modified simulated body fluid (m-SBF). This biomimetic method preserves the structural integrity and great tensile strength of collagen by reinforcing the collagen hydrogel with apatite nano-particles. Unidirectional aligned macro pores with a size of 63.8 to 344 μm are created by controlling the freezing rate and direction. The thickness of Col-Ap lamellae can be adjusted in the range 3.6 to 23 μm depending on the self-compression time. Furthermore, the multi-level lamellar structure has led to a twelve-fold increase in Young's modulus and a two-fold increase in the compression modulus along the aligned direction compared to a scaffold of the same composition with an isotropic equiaxed pore structure. Moreover, this novel lamellar scaffold supports the attachment and spreading of MC3T3-E1osteoblasts. Therefore, owing to the biomimetic composition, tunable structure, improved mechanical strength, and good biocompatibility of this novel scaffold, it has great potential to be used in bone tissue engineering applications. PMID:24999428

  19. Effects of implantation of three-dimensional engineered bone tissue with a vascular-like structure on repair of bone defects

    NASA Astrophysics Data System (ADS)

    Nishi, Masanori; Matsumoto, Rena; Dong, Jian; Uemura, Toshimasa

    2012-12-01

    Previously, to create an implantable bone tissue associated with blood vessels, we co-cultured rabbit bone marrow mesenchymal stem cells (MSCs) with MSC-derived endothelial cells (ECs) within a porous polylactic acid-based scaffold utilizing a rotating wall vessel (RWV) bioreactor. Here, this engineered tissue was orthotopically implanted into defects made in femurs of immunodeficient rats, and histological analysis were carried out to examine the repair of the damage and the formation of bone around the implant. The bone defects were better repaired in the implanted group than control group after 3 weeks. The results indicate that the engineered bone could repair bone defects.

  20. Bone tissue engineering in osteoporosis.

    PubMed

    Jakob, Franz; Ebert, Regina; Ignatius, Anita; Matsushita, Takashi; Watanabe, Yoshinobu; Groll, Juergen; Walles, Heike

    2013-06-01

    Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age.

  1. Vascularization in bone tissue engineering constructs

    PubMed Central

    Mercado-Pagán, Ángel E.; Stahl, Alexander M.; Shanjani, Yaser; Yang, Yunzhi

    2016-01-01

    Vascularization of large bone grafts is one of the main challenges of bone tissue engineering (BTE), and has held back the clinical translation of engineered bone constructs for two decades so far. The ultimate goal of vascularized BTE constructs is to provide a bone environment rich in functional vascular networks to achieve efficient osseointegration and accelerate restoration of function after implantation. To attain both structural and vascular integration of the grafts, a large number of biomaterials, cells, and biological cues have been evaluated. This review will present biological considerations for bone function restoration, contemporary approaches for clinical salvage of large bone defects and their limitations, state-of-the-art research on the development of vascularized bone constructs, and perspectives on evaluating and implementing novel BTE grafts in clinical practice. Success will depend on achieving full graft integration at multiple hierarchical levels, both between the individual graft components as well as between the implanted constructs and their surrounding host tissues. The paradigm of vascularized tissue constructs could not only revolutionize the progress of bone tissue engineering, but could also be readily applied to other fields in regenerative medicine for the development of new innovative vascularized tissue designs. PMID:25616591

  2. Modified silk fibroin scaffolds with collagen/decellularized pulp for bone tissue engineering in cleft palate: Morphological structures and biofunctionalities.

    PubMed

    Sangkert, Supaporn; Meesane, Jirut; Kamonmattayakul, Suttatip; Chai, Wen Lin

    2016-01-01

    Cleft palate is a congenital malformation that generates a maxillofacial bone defect around the mouth area. The creation of performance scaffolds for bone tissue engineering in cleft palate is an issue that was proposed in this research. Because of its good biocompatibility, high stability, and non-toxicity, silk fibroin was selected as the scaffold of choice in this research. Silk fibroin scaffolds were prepared by freeze-drying before immerging in a solution of collagen, decellularized pulp, and collagen/decellularized pulp. Then, the immersed scaffolds were freeze-dried. Structural organization in solution was observed by Atomic Force Microscope (AFM). The molecular organization of the solutions and crystal structure of the scaffolds were characterized by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD), respectively. The weight increase of the modified scaffolds and the pore size were determined. The morphology was observed by a scanning electron microscope (SEM). Mechanical properties were tested. Biofunctionalities were considered by seeding osteoblasts in silk fibroin scaffolds before analysis of the cell proliferation, viability, total protein assay, and histological analysis. The results demonstrated that dendrite structure of the fibrils occurred in those solutions. Molecular organization of the components in solution arranged themselves into an irregular structure. The fibrils were deposited in the pores of the modified silk fibroin scaffolds. The modified scaffolds showed a beta-sheet structure. The morphological structure affected the mechanical properties of the silk fibroin scaffolds with and without modification. Following assessment of the biofunctionalities, the modified silk fibroin scaffolds could induce cell proliferation, viability, and total protein particularly in modified silk fibroin with collagen/decellularized pulp. Furthermore, the histological analysis indicated that the cells could adhere in modified silk fibroin

  3. The materials used in bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Tereshchenko, V. P.; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M.

    2015-11-01

    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.

  4. The materials used in bone tissue engineering

    SciTech Connect

    Tereshchenko, V. P. Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M.

    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.

  5. Silk fibroin scaffolds with inverse opal structure for bone tissue engineering.

    PubMed

    Sommer, Marianne R; Vetsch, Jolanda R; Leemann, Jessica; Müller, Ralph; Studart, André R; Hofmann, Sandra

    2017-10-01

    How scaffold porosity, pore diameter and geometry influence cellular behavior is-although heavily researched - merely understood, especially in 3D. This is mainly caused by a lack of suitable, reproducible scaffold fabrication methods, with processes such as gas foaming, lyophilization or particulate leaching still being the standard. Here we propose a method to generate highly porous silk fibroin scaffolds with monodisperse spherical pores, namely inverse opals, and study their effect on cell behavior. These silk fibroin inverse opal scaffolds were compared to salt-leached silk fibroin scaffolds in terms of human mesenchymal stem cell response upon osteogenic differentiation signals. While cell number remained similar on both scaffold types, extracellular matrix mineralization nearly doubled on the newly developed scaffolds, suggesting a positive effect on cell differentiation. By using the very same material with comparable average pore diameters, this increase in mineral content can be attributed to either the differences in pore diameter distribution or the pore geometry. Although the exact mechanisms leading to enhanced mineralization in inverse opals are not yet fully understood, our results indicate that control over pore geometry alone can have a major impact on the bioactivity of a scaffold toward stem cell differentiation into bone tissue. © 2016 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2074-2084, 2017. © 2016 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

  6. Brown adipose tissue and bone

    PubMed Central

    Lidell, M E; Enerbäck, S

    2015-01-01

    Brown adipose tissue (BAT) is capable of transforming chemically stored energy, in the form of triglycerides, into heat. Recent studies have shown that metabolically active BAT is present in a large proportion of adult humans, where its activity correlates with a favorable metabolic status. Hence, the tissue is now regarded as an interesting target for therapies against obesity and associated diseases such as type 2 diabetes, the hypothesis being that an induction of BAT would be beneficial for these disease states. Apart from the association between BAT activity and a healthier metabolic status, later studies have also shown a positive correlation between BAT volume and both bone cross-sectional area and bone mineral density, suggesting that BAT might stimulate bone anabolism. The aim of this review is to give the reader a brief overview of the BAT research field and to summarize and discuss recent findings regarding BAT being a potential player in bone metabolism. PMID:27152171

  7. Bioactive scaffolds for bone and ligament tissue.

    PubMed

    Guarino, Vincenzo; Causa, Filippo; Ambrosio, Luigi

    2007-05-01

    Bone and ligament injuries present the greatest challenges in connective tissue regeneration. The design of materials for these applications lies at the forefront of material science and is the epitome of its current ambition. Indeed, its goal is to design and fabricate reproducible, bioactive and bioresorbable 3D scaffolds with tailored properties that are able to maintain their structure and integrity for predictable times, even under load-bearing conditions. Unfortunately, the mechanical properties of today's available porous scaffolds fall short of those exhibited by complex human tissues, such as bone and ligament. The manipulation of structural parameters in the design of scaffolds and their bioactivation, through the incorporation of soluble and insoluble signals capable of promoting cell activities, are discussed as possible strategies to improve the formation of new tissues both in vitro and in vivo. This review focuses on the different approaches adopted to develop bioactive composite systems for use as temporary scaffolds for bone and anterior ligament regeneration.

  8. Realistic 3D computer model of the gerbil middle ear, featuring accurate morphology of bone and soft tissue structures.

    PubMed

    Buytaert, Jan A N; Salih, Wasil H M; Dierick, Manual; Jacobs, Patric; Dirckx, Joris J J

    2011-12-01

    In order to improve realism in middle ear (ME) finite-element modeling (FEM), comprehensive and precise morphological data are needed. To date, micro-scale X-ray computed tomography (μCT) recordings have been used as geometric input data for FEM models of the ME ossicles. Previously, attempts were made to obtain these data on ME soft tissue structures as well. However, due to low X-ray absorption of soft tissue, quality of these images is limited. Another popular approach is using histological sections as data for 3D models, delivering high in-plane resolution for the sections, but the technique is destructive in nature and registration of the sections is difficult. We combine data from high-resolution μCT recordings with data from high-resolution orthogonal-plane fluorescence optical-sectioning microscopy (OPFOS), both obtained on the same gerbil specimen. State-of-the-art μCT delivers high-resolution data on the 3D shape of ossicles and other ME bony structures, while the OPFOS setup generates data of unprecedented quality both on bone and soft tissue ME structures. Each of these techniques is tomographic and non-destructive and delivers sets of automatically aligned virtual sections. The datasets coming from different techniques need to be registered with respect to each other. By combining both datasets, we obtain a complete high-resolution morphological model of all functional components in the gerbil ME. The resulting 3D model can be readily imported in FEM software and is made freely available to the research community. In this paper, we discuss the methods used, present the resulting merged model, and discuss the morphological properties of the soft tissue structures, such as muscles and ligaments.

  9. Bone reconstruction: from bioceramics to tissue engineering.

    PubMed

    El-Ghannam, Ahmed

    2005-01-01

    Over the past 30 years, an enormous array of biomaterials proposed as ideal scaffolds for cell growth have emerged, yet few have demonstrated clinical efficacy. Biomaterials, regardless of whether they are permanent or biodegradable, naturally occurring or synthetic, need to be biocompatible, ideally osteoinductive, osteoconductive, integrative, porous and mechanically compatible with native bone to fulfill their desired role in bone tissue engineering. These materials provide cell anchorage sites, mechanical stability and structural guidance and in vivo, provide the interface to respond to physiologic and biologic changes as well as to remodel the extracellular matrix in order to integrate with the surrounding native tissue. Calcium phosphate ceramics and bioactive glasses were introduced more than 30 years ago as bone substitutes. These materials are considered bioactive as they bond to bone and enhance bone tissue formation. The bioactivity property has been attributed to the similarity between the surface composition and structure of bioactive materials, and the mineral phase of bone. The drawback in using bioactive glasses and calcium phosphate ceramics is that close proximity to the host bone is necessary to achieve osteoconduction. Even when this is achieved, new bone growth is often strictly limited because these materials are not osteoinductive in nature. Bone has a vast capacity for regeneration from cells with stem cell characteristics. Moreover, a number of different growth factors including bone morphogenetic proteins, have been demonstrated to stimulate bone growth, collagen synthesis and fracture repair both in vitro and in vivo. Attempts to develop a tissue-engineering scaffold with both osteoconductivity and osteoinductivity have included loading osteoinductive proteins and/or osteogenic cells on the traditional bioactive materials. Yet issues that must be considered for the effective application of bioceramics in the field of tissue engineering

  10. Differential effects between the loss of MMP-2 and MMP-9 on structural and tissue-level properties of bone.

    PubMed

    Nyman, Jeffry S; Lynch, Conor C; Perrien, Daniel S; Thiolloy, Sophie; O'Quinn, Elizabeth C; Patil, Chetan A; Bi, Xiaohong; Pharr, George M; Mahadevan-Jansen, Anita; Mundy, Gregory R

    2011-06-01

    Matrix metalloproteinases (MMPs) are capable of processing certain components of bone tissue, including type 1 collagen, a determinant of the biomechanical properties of bone tissue, and they are expressed by osteoclasts and osteoblasts. Therefore, we posit that MMP activity can affect the ability of bone to resist fracture. To explore this possibility, we determined the architectural, compositional, and biomechanical properties of bones from wild-type (WT), Mmp2(-/-) , and Mmp9(-/-) female mice at 16 weeks of age. MMP-2 and MMP-9 have similar substrates but are expressed primarily by osteoblasts and osteoclasts, respectively. Analysis of the trabecular compartment of the tibia metaphysis by micro-computed tomography (µCT) revealed that these MMPs influence trabecular architecture, not volume. Interestingly, the loss of MMP-9 improved the connectivity density of the trabeculae, whereas the loss of MMP-2 reduced this parameter. Similar differential effects in architecture were observed in the L(5) vertebra, but bone volume fraction was lower for both Mmp2(-/-) and Mmp9(-/-) mice than for WT mice. The mineralization density and mineral-to-collagen ratio, as determined by µCT and Raman microspectroscopy, were lower in the Mmp2(-/-) bones than in WT control bones. Whole-bone strength, as determined by three-point bending or compression testing, and tissue-level modulus and hardness, as determined by nanoindentation, were less for Mmp2(-/-) than for WT bones. In contrast, the Mmp9(-/-) femurs were less tough with lower postyield deflection (more brittle) than the WT femurs. Taken together, this information reveals that MMPs play a complex role in maintaining bone integrity, with the cell type that expresses the MMP likely being a contributing factor to how the enzyme affects bone quality.

  11. Nanotechnology in bone tissue engineering.

    PubMed

    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.

  12. Multiscale fluid-structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold.

    PubMed

    Zhao, Feihu; Vaughan, Ted J; Mcnamara, Laoise M

    2015-04-01

    Recent studies have shown that mechanical stimulation, by means of flow perfusion and mechanical compression (or stretching), enhances osteogenic differentiation of mesenchymal stem cells and bone cells within biomaterial scaffolds in vitro. However, the precise mechanisms by which such stimulation enhances bone regeneration is not yet fully understood. Previous computational studies have sought to characterise the mechanical stimulation on cells within biomaterial scaffolds using either computational fluid dynamics or finite element (FE) approaches. However, the physical environment within a scaffold under perfusion is extremely complex and requires a multiscale and multiphysics approach to study the mechanical stimulation of cells. In this study, we seek to determine the mechanical stimulation of osteoblasts seeded in a biomaterial scaffold under flow perfusion and mechanical compression using multiscale modelling by two-way fluid-structure interaction and FE approaches. The mechanical stimulation, in terms of wall shear stress (WSS) and strain in osteoblasts, is quantified at different locations within the scaffold for cells of different attachment morphologies (attached, bridged). The results show that 75.4 % of scaffold surface has a WSS of 0.1-10 mPa, which indicates the likelihood of bone cell differentiation at these locations. For attached and bridged osteoblasts, the maximum strains are 397 and 177,200 με, respectively. Additionally, the results from mechanical compression show that attached cells are more stimulated (maximum strain = 22,600 με) than bridged cells (maximum strain = 10.000 με)Such information is important for understanding the biological response of osteoblasts under in vitro stimulation. Finally, a combination of perfusion and compression of a tissue engineering scaffold is suggested for osteogenic differentiation.

  13. [Structural and functional characteristics of bone tissue and blood cytokines in health and disease of the joints].

    PubMed

    Kariakina, E V; Norkin, I A; Gladkova, E V; Persova, E A; Matveeva, O V; Puchin'ian, D M

    2014-02-01

    Change of structural and functional state of bone in patients with primary osteoarthrosis of the hip joint compared to healthy individuals is characterized by decreased bone formation with a relative predominance of resorption. Osteopenic syndrome develops in the background of evident imbalance of a blood cytokine profile with increasing the level of proinflammatory and the variability of the level of anti-inflammatory cytokines.

  14. Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    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. PMID:26904121

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

    PubMed

    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.

  17. Elastic properties of a porous titanium-bone tissue composite.

    PubMed

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

    2015-01-01

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

  18. Biocomposites containing natural polymers and hydroxyapatite for bone tissue engineering.

    PubMed

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

    2010-07-01

    Bone tissue engineering is an alternative strategy to generate bone utilizing a combination of biomaterials and cells. Biomaterials that mimic the structure and composition of bone tissues at nanoscale are important for the development of bone tissue engineering applications. Natural or biopolymer-based composites containing chitin, chitosan, or collagen have advantages such as biocompatibility, biodegradability that are essential for bone tissue engineering. The inclusion of nanoparticles of hydroxyapatite (one of the most widely used bioceramic materials) into the biopolymer matrix improves the mechanical properties and incorporates the nanotopographic features that mimic the nanostructure of bone. This review summarizes the recent work on the development of biocomposites containing natural polymers with hydroxyapatite particles suitable for use in bone defects/bone regeneration. (c) 2010 Elsevier B.V. All rights reserved.

  19. [Scaffold-based Bone Tissue Engineering].

    PubMed

    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.

  20. Scaffolds based bone tissue engineering: the role of chitosan.

    PubMed

    Costa-Pinto, Ana Rita; Reis, Rui L; Neves, Nuno M

    2011-10-01

    As life expectancy increases, malfunction or loss of tissue caused by injury or disease leads to reduced quality of life in many patients at significant socioeconomic cost. Even though major progress has been made in the field of bone tissue engineering, present therapies, such as bone grafts, still have limitations. Current research on biodegradable polymers is emerging, combining these structures with osteogenic cells, as an alternative to autologous bone grafts. Different types of biodegradable materials have been proposed for the preparation of three-dimensional porous scaffolds for bone tissue engineering. Among them, natural polymers are one of the most attractive options, mainly due to their similarities with extracellular matrix, chemical versatility, good biological performance, and inherent cellular interactions. In this review, special attention is given to chitosan as a biomaterial for bone tissue engineering applications. An extensive literature survey was performed on the preparation of chitosan scaffolds and their in vitro biological performance as well as their potential to facilitate in vivo bone regeneration. The present review also aims to offer the reader a general overview of all components needed to engineer new bone tissue. It gives a brief background on bone biology, followed by an explanation of all components in bone tissue engineering, as well as describing different tissue engineering strategies. Moreover, also discussed are the typical models used to evaluate in vitro functionality of a tissue-engineered construct and in vivo models to assess the potential to regenerate bone tissue are discussed.

  1. The micro-architecture of human cancellous bone from fracture neck of femur patients in relation to the structural integrity and fracture toughness of the tissue.

    PubMed

    Greenwood, C; Clement, J G; Dicken, A J; Evans, J P O; Lyburn, I D; Martin, R M; Rogers, K D; Stone, N; Adams, G; Zioupos, P

    2015-12-01

    Osteoporosis is clinically assessed from bone mineral density measurements using dual energy X-ray absorption (DXA). However, these measurements do not always provide an accurate fracture prediction, arguably because DXA does not grapple with 'bone quality', which is a combined result of microarchitecture, texture, bone tissue properties, past loading history, material chemistry and bone physiology in reaction to disease. Studies addressing bone quality are comparatively few if one considers the potential importance of this factor. They suffer due to low number of human osteoporotic specimens, use of animal proxies and/or the lack of differentiation between confounding parameters such as gender and state of diseased bone. The present study considers bone samples donated from patients (n = 37) who suffered a femoral neck fracture and in this very well defined cohort we have produced in previous work fracture toughness measurements (FT) which quantify its ability to resist crack growth which reflects directly the structural integrity of the cancellous bone tissue. We investigated correlations between BV/TV and other microarchitectural parameters; we examined effects that may suggest differences in bone remodelling between males and females and compared the relationships with the FT properties. The data crucially has shown that TbTh, TbSp, SMI and TbN may provide a proxy or surrogate for BV/TV. Correlations between FT critical stress intensity values and microarchitecture parameters (BV/TV, BS/TV, TbN, BS/BV and SMI) for osteoporotic cancellous tissue were observed and are for the first time reported in this study. Overall, this study has not only highlighted that the fracture model based upon BMD could potentially be improved with inclusion of other microarchitecture parameters, but has also given us clear clues as to which of them are more influential in this role.

  2. Polymer-ceramic spiral structured scaffolds for bone tissue engineering: effect of hydroxyapatite composition on human fetal osteoblasts.

    PubMed

    Zhang, Xiaojun; Chang, Wei; Lee, Paul; Wang, Yuhao; Yang, Min; Li, Jun; Kumbar, Sangamesh G; Yu, Xiaojun

    2014-01-01

    For successful bone tissue engineering, a scaffold needs to be osteoconductive, porous, and biodegradable, thus able to support attachment and proliferation of bone cells and guide bone formation. Recently, hydroxyapatites (HA), a major inorganic component of natural bone, and biodegrade polymers have drawn much attention as bone scaffolds. The present study was designed to investigate whether the bone regenerative properties of nano-HA/polycaprolactone (PCL) spiral scaffolds are augmented in an HA dose dependent manner, thereby establishing a suitable composition as a bone formation material. Nano-HA/PCL spiral scaffolds were prepared with different weight ratios of HA and PCL, while porosity was introduced by a modified salt leaching technique. Human fetal osteoblasts (hFOBs) were cultured on the nano-HA/PCL spiral scaffolds up to 14 days. Cellular responses in terms of cell adhesion, viability, proliferation, differentiation, and the expression of bone-related genes were investigated. These scaffolds supported hFOBs adhesion, viability and proliferation. Cell proliferation trend was quite similar on polymer-ceramic and neat polymer spiral scaffolds on days 1, 7, and 14. However, the significantly increased amount of alkaline phosphatase (ALP) activity and mineralized matrix synthesis was evident on the nano-HA/PCL spiral scaffolds. The HA composition in the scaffolds showed a significant effect on ALP and mineralization. Bone phenotypic markers such as bone sialoprotein (BSP), osteonectin (ON), osteocalcin (OC), and type I collagen (Col-1) were semi-quantitatively estimated by reverse transcriptase polymerase chain reaction analysis. All of these results suggested the osteoconductive characteristics of HA/PCL nanocomposite and cell maturation were HA dose dependent. For instance, HA∶PCL = 1∶4 group showed significantly higher ALP mineralization and elevated levels of BSP, ON, OC and Col-I expression as compared other lower or higher ceramic ratios

  3. Polymer-Ceramic Spiral Structured Scaffolds for Bone Tissue Engineering: Effect of Hydroxyapatite Composition on Human Fetal Osteoblasts

    PubMed Central

    Zhang, Xiaojun; Chang, Wei; Lee, Paul; Wang, Yuhao; Yang, Min; Li, Jun; Kumbar, Sangamesh G.; Yu, Xiaojun

    2014-01-01

    For successful bone tissue engineering, a scaffold needs to be osteoconductive, porous, and biodegradable, thus able to support attachment and proliferation of bone cells and guide bone formation. Recently, hydroxyapatites (HA), a major inorganic component of natural bone, and biodegrade polymers have drawn much attention as bone scaffolds. The present study was designed to investigate whether the bone regenerative properties of nano-HA/polycaprolactone (PCL) spiral scaffolds are augmented in an HA dose dependent manner, thereby establishing a suitable composition as a bone formation material. Nano-HA/PCL spiral scaffolds were prepared with different weight ratios of HA and PCL, while porosity was introduced by a modified salt leaching technique. Human fetal osteoblasts (hFOBs) were cultured on the nano-HA/PCL spiral scaffolds up to 14 days. Cellular responses in terms of cell adhesion, viability, proliferation, differentiation, and the expression of bone-related genes were investigated. These scaffolds supported hFOBs adhesion, viability and proliferation. Cell proliferation trend was quite similar on polymer-ceramic and neat polymer spiral scaffolds on days 1, 7, and 14. However, the significantly increased amount of alkaline phosphatase (ALP) activity and mineralized matrix synthesis was evident on the nano-HA/PCL spiral scaffolds. The HA composition in the scaffolds showed a significant effect on ALP and mineralization. Bone phenotypic markers such as bone sialoprotein (BSP), osteonectin (ON), osteocalcin (OC), and type I collagen (Col-1) were semi-quantitatively estimated by reverse transcriptase polymerase chain reaction analysis. All of these results suggested the osteoconductive characteristics of HA/PCL nanocomposite and cell maturation were HA dose dependent. For instance, HA∶PCL = 1∶4 group showed significantly higher ALP mineralization and elevated levels of BSP, ON, OC and Col-I expression as compared other lower or higher ceramic ratios

  4. Structural features of bone marrow

    PubMed Central

    Romaniuk, Anatolii; Lyndina, Yuliia; Sikora, Vladyslav; Lyndin, Mykola; Karpenko, Ludmyla; Gladchenko, Oksana; Masalitin, Igor

    2016-01-01

    Purpose This article is devoted to the investigation of the structural features of the bone marrow of mature rats. Materials and methods The investigation of the structural features of the bone marrow was performed on the femurs of the mature male rats. General structure of the organ was studied with hematoxylin–eosin and Van Gieson staining of samples. Certain features of the bone marrow structure were studied using immunohistochemical method (CD3, CD79α, S100, myeloperoxidase, and cyclin D1). Results We can state that stromal–parenchymal structure is typical for the bone marrow of rats as for any other organ. The stromal component is presented with bone tissue (48.8 ± 3.3% at epiphyses), the net of blood vessels (18.7 ± 2.1%), fat tissue (11 ± 2%), fibrous tissue (0.7 ± 0.2%), and the network of reticular fibers. Hematopoietic tissue covers 20.9 ± 3.7% at the femoral epiphyses and 69.6 ± 2.2% at diaphysis. Among these tissues, myelopoiesis occupies 74.2 ± 4.7%, erythropoiesis – 24.3 ± 4.7%, and lymphopoiesis – less than 5%. Megalokaryocytes take 0.1–0.3%. Conclusion Considering the lack of significant anatomical, morphological, and histological differences of red bone marrow of rats and humans, we can state that hematopoiesis in rats takes place on the basis of the same principles as in humans, although it has certain mechanisms. PMID:28203394

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

    PubMed

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

    2017-01-01

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

  6. [FLUORESCENCE DISTRIBUTION IN BONE AND CARTILAGE TISSUE BY SECTIONING OF FROZEN UNDECALCIFIED BONE].

    PubMed

    Sun, Zhen; Yin, Heyong; Sui, Xiang; Yu, Xiaoming; Peng, Jiang; Wang, Yu; Wang, Aiyuan; Guo, Quanyi; Liu Shuyun; Meng, Haoye; Lu, Shibi

    2015-11-01

    To introduce a technique of frozen sections for undecalcified bone and discuss its feasiblity by observing the fluorescence distribution of the bone and cartilage. The male Sprague Dawley transgenic rats at the age of 8 weeks, which express green fluoreschent protein were selected to isolate the whole knee sectioned by teh undecalicified bone fronze section techynique. Under the fluorescence and light microscopy, the fluorescence and structure were observed within the organization of slice. Immunohistochemical staining (collagen type I and II, He staining, toluidine blue staining, and Alizarin red staining were performed to observe the distribution of fluorescent substance and cartilage and bone structure. The thickness of sections prepared by this technology was 6 µm. General observation showed that the structure of secioned joint was complete. Under the light microscope, the morphology of cartilage cells, the arrangement of subchondral bone, and trabecular bone traveling could be clearly distinguished. Under fluorescence microscope, green fluorescence was shonw in the joint soft tissue, cartilage tissue, and bone tissue; collagen type I expressed in the bone tissue, collage type II in cartilage tissue. HE staining and toluidine blue staining could clearly distinguish the morphology of the cartilage layer. Alizarin red staining showed the structural integrity of subchondral bone plate and the organization within the meniscus, and proximal tibia cortical bone continuity. The fluorescence distribution can be directly observe in the bone and cartilage by sectioning of frozen undecalcified bone. This new technology can shorten the cycle of preparing sections.

  7. Bone as a Structural Material.

    PubMed

    Zimmermann, Elizabeth A; Ritchie, Robert O

    2015-06-24

    As one of the most important natural materials, cortical bone is a composite material comprising assemblies of tropocollagen molecules and nanoscale hydroxyapatite mineral crystals, forming an extremely tough, yet lightweight, adaptive and multi-functional material. Bone has evolved to provide structural support to organisms, and therefore its mechanical properties are vital physiologically. Like many mineralized tissues, bone can resist deformation and fracture from the nature of its hierarchical structure, which spans molecular to macroscopic length-scales. In fact, bone derives its fracture resistance with a multitude of deformation and toughening mechanisms that are active at most of these dimensions. It is shown that bone's strength and ductility originate primarily at the scale of the nano to submicrometer structure of its mineralized collagen fibrils and fibers, whereas bone toughness is additionally generated at much larger, micro- to near-millimeter, scales from crack-tip shielding associated with interactions between the crack path and the microstructure. It is further shown how the effectiveness with which bone's structural features can resist fracture at small to large length-scales can become degraded by biological factors such as aging and disease, which affect such features as the collagen cross-linking environment, the homogeneity of mineralization, and the density of the osteonal structures.

  8. Highly bioactive polysiloxane modified bioactive glass-poly(ethylene glycol) hybrids monoliths with controlled surface structure for bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Chen, Jing; Que, Wenxiu; Xing, Yonglei; Lei, Bo

    2015-03-01

    Crack-free monoliths with controllable surface microstructure have high bioactivities and therefore potential applications in bone tissue regeneration. In this paper, crack-free polydimethylsiloxane-modified bioactive glass-poly (ethylene glycol) (PDMS-BG-PEG) hybrids monoliths were fabricated via using a modified sol-gel process. Results show that the addition of PEG plays an important part in the formation of crack-free and gelation of the monoliths, and surface microstructures of the as-prepared hybrid monoliths were significantly influenced by the concentration and molecular weight of PEG. The samples obtained from PEG 300 had porous surface result in higher bioactivity (apatite formation) in simulated body fluid (SBF), while the samples obtained from PEG 600 had the smooth surface and inhibited the formation of apatite layer in SBF. These as-prepared hybrid monoliths can be used as a good candidate of implant and scaffold for highly efficient bone tissue regeneration.

  9. Multiscale modeling of bone tissue with surface and permeability control.

    PubMed

    Gonçalves Coelho, Pedro; Rui Fernandes, Paulo; Carriço Rodrigues, Helder

    2011-01-11

    Natural biological materials usually present a hierarchical arrangement with various structural levels. The biomechanical behavior of the complex hierarchical structure of bone is investigated with models that address the various levels corresponding to different scales. Models that simulate the bone remodeling process concurrently at different scales are in development. We present a multiscale model for bone tissue adaptation that considers the two top levels, whole bone and trabecular architecture. The bone density distribution is calculated at the macroscale (whole bone) level, and the trabecular structure at the microscale level takes into account its mechanical properties as well as surface density and permeability. The bone remodeling process is thus formulated as a material distribution problem at both scales. At the local level, the biologically driven information of surface density and permeability characterizes the trabecular structure. The model is tested by a three-dimensional simulation of bone tissue adaptation for the human femur. The density distribution of the model shows good agreement with the actual bone density distribution. Permeability at the microstructural level assures interconnectivity of pores, which mimics the interconnectivity of trabecular bone essential for vascularization and transport of nutrients. The importance of this multiscale model relays on the flexibility to control the morphometric parameters that characterize the trabecular structure. Therefore, the presented model can be a valuable tool to define bone quality, to assist with diagnosis of osteoporosis, and to support the development of bone substitutes.

  10. VEGF expression in mesenchymal stem cells promotes bone formation of tissue-engineered bones.

    PubMed

    Liu, Boling; Li, Xihai; Liang, Guiqing; Liu, Xianxiang

    2011-01-01

    The purpose of this study was to investigate the in vivo vascularization and bone formation activity of tissue-engineered bone constructed using bone marrow mesenchymal stem cells (MSCs) transfected with vascular endothelial growth factor (VEGF). The expression of VEGF165 in rat bone marrow MSCs was confirmed using RT-PCR and immunohistochemistry. The MSCs were cultured together with nano-hydroxyapatite/collagen (NHAC) to form tissue-engineered bone. Untransfected MSCs were used as controls. The mice were sacrificed, and the bone xenografts were analyzed using immunohistochemistry and quantified for the degree of vascularization and new bone formation. Based on our results, expression of the VEGF165 gene was detected using RT-PCR and immunohistochemistry following transfection and 4 weeks of selection. The co-cultured NHAC- and VEGF-transfected MSCs had significantly higher alkaline phosphatase (AP) activity compared to the controls (P<0.05). In the mice that received the tissue-engineered bone xenografts, clumps of cartilage cells, irregular bone-like tissue and microvessels were observed. The growth of these structures progressed with time. In the control mice, however, only small amounts of bone-like and fibrotic tissue were observed. The differences between the control and experimental groups were statistically significant (P<0.05). In conclusion, VEGF165‑transfected bone marrow MSCs promotes vascularization of tissue-engineered bone and ectopic osteogenesis.

  11. Chitosan-based scaffolds for bone tissue engineering

    PubMed Central

    Levengood, Sheeny Lan; Zhang, Miqin

    2014-01-01

    Bone defects requiring grafts to promote healing are frequently occurring and costly problems in health care. Chitosan, a biodegradable, naturally occurring polymer, has drawn considerable attention in recent years as scaffolding material in tissue engineering and regenerative medicine. Chitosan is especially attractive as a bone scaffold material because it supports the attachment and proliferation of osteoblast cells as well as formation of mineralized bone matrix. In this review, we discuss the fundamentals of bone tissue engineering and the unique properties of chitosan as a scaffolding material to treat bone defects for hard tissue regeneration. We present the common methods for fabrication and characterization of chitosan scaffolds, and discuss the influence of material preparation and addition of polymeric or ceramic components or biomolecules on chitosan scaffold properties such as mechanical strength, structural integrity, and functional bone regeneration. Finally, we highlight recent advances in development of chitosan-based scaffolds with enhanced bone regeneration capability. PMID:24999429

  12. Osteocyte and bone structure.

    PubMed

    Klein-Nulend, Jenneke; Nijweide, Peter J; Burger, Elisabeth H

    2003-06-01

    The osteocyte is the most abundant cell type of bone. There are approximately 10 times as many osteocytes as osteoblasts in adult human bone, and the number of osteoclasts is only a fraction of the number of osteoblasts. Our current knowledge of the role of osteocytes in bone metabolism is far behind our insight into the properties and functions of the osteoblasts and osteoclasts. However, the striking structural design of bone predicts an important role for osteocytes in determining bone structure. Over the past several years, the role of osteocytes as the professional mechanosensory cells of bone, and the lacunocanalicular porosity as the structure that mediates mechanosensing have become clear. Strain-derived flow of interstitial fluid through this porosity seems to mechanically activate the osteocytes, as well as ensure transport of cell signaling molecules, nutrients, and waste products. This concept explains local bone gain and loss--as well as remodeling in response to fatigue damage--as processes supervised by mechanosensitive osteocytes. Alignment during remodeling seems to occur as a result of the osteocyte's sensing different canalicular flow patterns around the cutting cone and reversal zone during loading, therefore determining the bone's structure.

  13. Carbon Nanostructures in Bone Tissue Engineering

    PubMed Central

    Perkins, Brian Lee; Naderi, Naghmeh

    2016-01-01

    Background: Recent advances in developing biocompatible materials for treating bone loss or defects have dramatically changed clinicians’ reconstructive armory. Current clinically available reconstructive options have certain advantages, but also several drawbacks that prevent them from gaining universal acceptance. A wide range of synthetic and natural biomaterials is being used to develop tissue-engineered bone. Many of these materials are currently in the clinical trial stage. Methods: A selective literature review was performed for carbon nanostructure composites in bone tissue engineering. Results: Incorporation of carbon nanostructures significantly improves the mechanical properties of various biomaterials to mimic that of natural bone. Recently, carbon-modified biomaterials for bone tissue engineering have been extensively investigated to potentially revolutionize biomaterials for bone regeneration. Conclusion: This review summarizes the chemical and biophysical properties of carbon nanostructures and discusses their functionality in bone tissue regeneration. PMID:28217212

  14. Cell interactions in bone tissue engineering.

    PubMed

    Pirraco, R P; Marques, A P; Reis, R L

    2010-01-01

    Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

  15. Bioactive scaffold for bone tissue engineering: An in vivo study

    NASA Astrophysics Data System (ADS)

    Livingston, Treena Lynne

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

  16. Restoration of jaw bone tissue defect using osteoplastic material.

    PubMed

    Grdzelidze, T; Machavariani, A; Menabde, G; Gvelesiani, N; Amiranashvili, I

    2014-02-01

    The aim of the study was to repair mandibular bone defect using BIO-OSS artificial bone implantation. The experiment was conducted on 30 white laboratory rats. Defect in the bone of lower jaw was created surgically. Animals were divided into 2 groups. 15 animals were allocated in control group. Another 15 animals were allocated in the BIO-OSS treatment group. analysis revealed bone defect in 6-month after modeling of bone defect. There was no pronounced proliferation of connective tissue visible in the defect area. Treatment group: In the samples of treated group, BIO-OSS bone mass formed basophilic fiber-like structures. It was surrounded with the thin proliferative connective and granulation tissues. proposed technique of bone defect reconstruction is an effective and sustainable method and can be recommended for wider use in clinical practice.

  17. Bone tissue engineering with human stem cells

    PubMed Central

    2010-01-01

    Treatment of extensive bone defects requires autologous bone grafting or implantation of bone substitute materials. An attractive alternative has been to engineer fully viable, biological bone grafts in vitro by culturing osteogenic cells within three-dimensional scaffolds, under conditions supporting bone formation. Such grafts could be used for implantation, but also as physiologically relevant models in basic and translational studies of bone development, disease and drug discovery. A source of human cells that can be derived in large numbers from a small initial harvest and predictably differentiated into bone forming cells is critically important for engineering human bone grafts. We discuss the characteristics and limitations of various types of human embryonic and adult stem cells, and their utility for bone tissue engineering. PMID:20637059

  18. Tissue Microarray Analysis Applied to Bone Diagenesis

    PubMed Central

    Mello, Rafael Barrios; Silva, Maria Regina Regis; Alves, Maria Teresa Seixas; Evison, Martin Paul; Guimarães, Marco Aurelio; Francisco, Rafaella Arrabaca; Astolphi, Rafael Dias; Iwamura, Edna Sadayo Miazato

    2017-01-01

    Taphonomic processes affecting bone post mortem are important in forensic, archaeological and palaeontological investigations. In this study, the application of tissue microarray (TMA) analysis to a sample of femoral bone specimens from 20 exhumed individuals of known period of burial and age at death is described. TMA allows multiplexing of subsamples, permitting standardized comparative analysis of adjacent sections in 3-D and of representative cross-sections of a large number of specimens. Standard hematoxylin and eosin, periodic acid-Schiff and silver methenamine, and picrosirius red staining, and CD31 and CD34 immunohistochemistry were applied to TMA sections. Osteocyte and osteocyte lacuna counts, percent bone matrix loss, and fungal spheroid element counts could be measured and collagen fibre bundles observed in all specimens. Decalcification with 7% nitric acid proceeded more rapidly than with 0.5 M EDTA and may offer better preservation of histological and cellular structure. No endothelial cells could be detected using CD31 and CD34 immunohistochemistry. Correlation between osteocytes per lacuna and age at death may reflect reported age-related responses to microdamage. Methodological limitations and caveats, and results of the TMA analysis of post mortem diagenesis in bone are discussed, and implications for DNA survival and recovery considered. PMID:28051148

  19. Bone tissue remodeling and development: focus on matrix metalloproteinase functions.

    PubMed

    Paiva, Katiucia Batista Silva; Granjeiro, José Mauro

    2014-11-01

    Bone-forming cells originate from distinct embryological layers, mesoderm (axial and appendicular bones) and ectoderm (precursor of neural crest cells, which mainly form facial bones). These cells will develop bones by two principal mechanisms: intramembranous and endochondral ossification. In both cases, condensation of multipotent mesenchymal cells occurs, at the site of the future bone, which differentiate into bone and cartilage-forming cells. During long bone development, an initial cartilaginous template is formed and replaced by bone in a coordinated and refined program involving chondrocyte proliferation and maturation, vascular invasion, recruitment of adult stem cells and intense remodeling of cartilage and bone matrix. Matrix metalloproteinases (MMPs) are the most important enzymes for cleaving structural components of the extracellular matrix (ECM), as well as other non-ECM molecules in the ECM space, pericellular perimeter and intracellularly. Thus, the bioactive molecules generated act on several biological events, such as development, tissue remodeling and homeostasis. Since the discovery of collagenase in bone cells, more than half of the MMP members have been detected in bone tissues under both physiological and pathological conditions. Pivotal functions of MMPs during development and bone regeneration have been revealed by knockout mouse models, such as chondrocyte proliferation and differentiation, osteoclast recruitment and function, bone modeling, coupling of bone resorption and formation (bone remodeling), osteoblast recruitment and survival, angiogenesis, osteocyte viability and function (biomechanical properties); as such alterations in MMP function may alter bone quality. In this review, we look at the principal properties of MMPs and their inhibitors (TIMPs and RECK), provide an up-date on their known functions in bone development and remodeling and discuss their potential application to Bone Bioengineering. Copyright © 2014 Elsevier Inc

  20. Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

    PubMed Central

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

    2016-01-01

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

  1. Differences in compact bone tissue microscopic structure between adult humans (Homo sapiens) and Assam macaques (Macaca assamensis).

    PubMed

    Nganvongpanit, Korakot; Phatsara, Manussabhorn; Settakorn, Jongkolnee; Mahakkanukrauh, Pasuk

    2015-09-01

    This study investigated the osteon structure of adult humans and Assam macaques, which served as a nonhuman primate model, to find an adequate key for species identification. Samples of compact bone from humans (n=5) and Assam macaques (n=5) - including humerus (n=20), radius (n=20), ulna (n=20), femur (n=20), tibia (n=20) and fibula (n=20) - were processed using conventional histological techniques. 100 secondary osteons from each sample were evaluated under light microscopy. Parameter measurements included: diameter, perimeter and area of Haversian canal and osteon; distance between centers of Haversian canals; and ratio between diameter of Haversian canal and osteon. Four parameters, including diameters and areas of Haversian canal and osteon, demonstrated significantly higher (P<0.05) values in humans than in Assam macaques. Therefore, compact bone microstructure could thus be used as a potential tool to differentiate human and nonhuman primates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing.

    PubMed

    Pang, Yonggang; Tsigkou, Olga; Spencer, Joel A; Lin, Charles P; Neville, Craig; Grottkau, Brian

    2015-10-01

    Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (D,L-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad

  3. Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing

    PubMed Central

    Pang, Yonggang; Tsigkou, Olga; Spencer, Joel A.; Lin, Charles P.; Neville, Craig

    2015-01-01

    Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (d,l-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad

  4. Designs from the deep: marine organisms for bone tissue engineering.

    PubMed

    Clarke, S A; Walsh, P; Maggs, C A; Buchanan, F

    2011-01-01

    Current strategies for bone repair have accepted limitations and the search for synthetic graft materials or for scaffolds that will support ex vivo bone tissue engineering continues. Biomimetic strategies have led to the investigation of naturally occurring porous structures as templates for bone growth. The marine environment is rich in mineralizing organisms with porous structures, some of which are currently being used as bone graft materials and others that are in early stages of development. This review describes the current evidence available for these organisms, considers the relative promise of each and suggests potential future directions. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Biomimetic nanofibrous scaffolds for bone tissue engineering

    PubMed Central

    Holzwarth, Jeremy M.; Ma, Peter X.

    2011-01-01

    Bone tissue engineering is a highly interdisciplinary field that seeks to tackle the most challenging bone-related clinical issues. The major components of bone tissue engineering are the scaffold, cells, and growth factors. This review will focus on the scaffold and recent advancements in developing scaffolds that can mimic the natural extracellular matrix of bone. Specifically, these novel scaffolds mirror the nanofibrous collagen network that comprises the majority of the non-mineral portion of bone matrix. Using two main fabrication techniques, electrospinning and thermally-induced phase separation, and incorporating bone-like minerals, such as hydroxyapatite, composite nanofibrous scaffolds can improve cell adhesion, stem cell differentiation, and tissue formation. This review will cover the two main processing techniques and how they are being applied to fabricate scaffolds for bone tissue engineering. It will then cover how these scaffolds can enhance the osteogenic capabilities of a variety of cell types and survey the ability of the constructs to support the growth of clinically relevant bone tissue. PMID:21944829

  6. Is Bone Tissue Really Affected by Swimming? A Systematic Review

    PubMed Central

    Gómez-Bruton, Alejandro; Gónzalez-Agüero, Alejandro; Gómez-Cabello, Alba; Casajús, José A.; Vicente-Rodríguez, Germán

    2013-01-01

    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. PMID:23950908

  7. Nanostructured scaffolds for bone tissue engineering.

    PubMed

    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.

  8. Alginate/nanohydroxyapatite scaffolds with designed core/shell structures fabricated by 3D plotting and in situ mineralization for bone tissue engineering.

    PubMed

    Luo, Yongxiang; Lode, Anja; Wu, Chengtie; Chang, Jiang; Gelinsky, Michael

    2015-04-01

    Composite scaffolds, especially polymer/hydroxyapatite (HAP) composite scaffolds with predesigned structures, are promising materials for bone tissue engineering. Various methods including direct mixing of HAP powder with polymers or incubating polymer scaffolds in simulated body fluid for preparing polymer/HAP composite scaffolds are either uncontrolled or require long times of incubation. In this work, alginate/nano-HAP composite scaffolds with designed pore parameters and core/shell structures were fabricated using 3D plotting technique and in situ mineralization under mild conditions (at room temperature and without the use of any organic solvents). Light microscopy, scanning electron microscopy, microcomputer tomography, X-ray diffraction, and Fourier transform infrared spectroscopy were applied to characterize the fabricated scaffolds. Mechanical properties and protein delivery of the scaffolds were evaluated, as well as the cell response to the scaffolds by culturing human bone-marrow-derived mesenchymal stem cells (hBMSC). The obtained data indicate that this method is suitable to fabricate alginate/nano-HAP composite scaffolds with a layer of nano-HAP, coating the surface of the alginate strands homogeneously and completely. The surface mineralization enhanced the mechanical properties and improved the cell attachment and spreading, as well as supported sustaining protein release, compared to pure alginate scaffolds without nano-HAP shell layer. The results demonstrated that the method provides an interesting option for bone tissue engineering application.

  9. Chitosan composites for bone tissue engineering--an overview.

    PubMed

    Venkatesan, Jayachandran; Kim, Se-Kwon

    2010-08-02

    Bone contains considerable amounts of minerals and proteins. Hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂] 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 prostheses 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.

  10. Variability and Anisotropy of Fracture Toughness of Cortical Bone Tissue

    NASA Astrophysics Data System (ADS)

    Abdel-Wahab, Adel; Nordin, Norhaziqah; Silberschmidt, Vadim

    2012-08-01

    Bones form protective and load-bearing framework of the body. Therefore, their structural integrity is vital for the quality of life. Unfortunately, bones can only sustain a load until a certain limit, beyond which they fail. Therefore, it is essential to study their mechanical and fracture behaviours in order to get an in-depth understanding of the origins of its fracture resistance that, in turn, can assist diagnosis and prevention of bone's trauma. This can be achieved by studying mechanical properties of bone, such as its fracture toughness. Generally, most of bone fractures occur for long bones that consist mostly of cortical bone. Therefore, in this study, only a cortical bone tissue was studied. Since this tissue has an anisotropic behaviour and possesses hierarchical and complex structure, in this paper, an experimental analysis for the fracture toughness of cortical bone tissue is presented in terms of J-integral. The data was obtained using single-edge-notch bending (SENB) cortical specimens of bone tested in a three-point bending setup. Variability of values of fracture toughness was investigated by testing specimens cut from different cortex positions of bovine femur called anterior, posterior, medial, and lateral. In addition, anisotropy ratios of fracture toughness were considered by examining specimens cut from three different orientations: longitudinal, transverse and radial. Moreover, in order to link cortical bone fracture mechanisms with its underlying microstructure, fracture surfaces of specimens from different cortices and along different orientations were studied. Experimental results of this study provide a clear understanding of both variability and anisotropy of cortical bone tissue with regard to its fracture toughness.

  11. [Cell sheet technology and its application in bone tissue engineering].

    PubMed

    Chen, Yali; Zhou, Nuo; Huang, Xuanping

    2012-09-01

    To review the progress of cell sheet technology (CST) and its application in bone tissue engineering. The literature concerning CST and its application was extensively reviewed and analyzed. CST using temperature-responsive culture dishes is applied to avoid the shortcomings of traditional tissue engineering. All cultured cells are harvested as intact sheets along with their deposited extracellular matrix. Avoiding the use of proteolytic enzymes, cell sheet composed of the cells and extracellular matrix derived from the cells, and remained the relative protein and biological activity factors. Consequently, cell sheet can provide a suitable microenvironment for the bone regeneration in vivo. With CST, cell sheet engineering is allowed for tissue regeneration by the creation of three-dimensional structures via the layering of individual cell sheets, be created by wrapping scaffold with cell sheets, or be created by folding the cell sheets, showing great potential in tissue engineered bone. Constructing tissue engineered bone using CST and traditional method of bone tissue engineering will promote the development of the bone tissue engineering.

  12. Dentin Matrix Proteins in Bone Tissue Engineering.

    PubMed

    Ravindran, Sriram; George, Anne

    2015-01-01

    Dentin and bone are mineralized tissue matrices comprised of collagen fibrils and reinforced with oriented crystalline hydroxyapatite. Although both tissues perform different functionalities, they are assembled and orchestrated by mesenchymal cells that synthesize both collagenous and noncollagenous proteins albeit in different proportions. The dentin matrix proteins (DMPs) have been studied in great detail in recent years due to its inherent calcium binding properties in the extracellular matrix resulting in tissue calcification. Recent studies have shown that these proteins can serve both as intracellular signaling proteins leading to induction of stem cell differentiation and also function as nucleating proteins in the extracellular matrix. These properties make the DMPs attractive candidates for bone and dentin tissue regeneration. This chapter will provide an overview of the DMPs, their functionality and their proven and possible applications with respect to bone tissue engineering.

  13. Dentin Matrix Proteins in Bone Tissue Engineering

    PubMed Central

    Ravindran, Sriram

    2016-01-01

    Dentin and bone are mineralized tissue matrices comprised of collagen fibrils and reinforced with oriented crystalline hydroxyapatite. Although both tissues perform different functionalities, they are assembled and orchestrated by mesenchymal cells that synthesize both collagenous and noncollagenous proteins albeit in different proportions. The dentin matrix proteins (DMPs) have been studied in great detail in recent years due to its inherent calcium binding properties in the extracellular matrix resulting in tissue calcification. Recent studies have shown that these proteins can serve both as intracellular signaling proteins leading to induction of stem cell differentiation and also function as nucleating proteins in the extracellular matrix. These properties make the DMPs attractive candidates for bone and dentin tissue regeneration. This chapter will provide an overview of the DMPs, their functionality and their proven and possible applications with respect to bone tissue engineering. PMID:26545748

  14. Orthopaedic tissue engineering and bone regeneration.

    PubMed

    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.

  15. Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

    PubMed Central

    Chiara, Gardin; Letizia, Ferroni; Lorenzo, Favero; Edoardo, Stellini; Diego, Stomaci; Stefano, Sivolella; Eriberto, Bressan; Barbara, Zavan

    2012-01-01

    Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM) of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs) from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering. PMID:22312283

  16. Bone tissue regeneration: the role of scaffold geometry.

    PubMed

    Zadpoor, Amir A

    2015-02-01

    The geometry of porous scaffolds that are used for bone tissue engineering and/or bone substitution has recently been shown to significantly influence the cellular response and the rate of bone tissue regeneration. Most importantly, it has been shown that the rate of tissue generation increases with curvature and is much larger on concave surfaces as compared to convex and planar surfaces. In this work, recent discoveries concerning the effects of geometrical features of porous scaffolds such as surface curvature, pore shape, and pore size on the cellular response and bone tissue regeneration process are reviewed. In addition to reviewing the recent experimental observations, we discuss the mechanisms through which geometry affects the bone tissue regeneration process. Of particular interest are the theoretical models that have been developed to explain the role of geometry in the bone tissue regeneration process. We then follow with a section on the implications of the observed phenomena for geometrical design of porous scaffolds including the application of predictive computational models in geometrical design of porous scaffolds. Moreover, some geometrical concepts in the design of porous scaffolds such as minimal surfaces and porous structures with geometrical gradients that have not been explored before are suggested for future studies. We especially focus on the porous scaffolds manufactured using additive manufacturing techniques where the geometry of the porous scaffolds could be precisely controlled. The paper concludes with a general discussion of the current state-of-the-art and recommendations for future research.

  17. RhBMP-2-loaded calcium silicate/calcium phosphate cement scaffold with hierarchically porous structure for enhanced bone tissue regeneration.

    PubMed

    Zhang, Jing; Zhou, Huanjun; Yang, Kai; Yuan, Yuan; Liu, Changsheng

    2013-12-01

    Calcium phosphate cement scaffold (CPC) has been widely used as bone graft substitutes, but undesirable osteoinductivity and slow degradability greatly hamper their clinic application. To address these problems, a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium silicate/calcium phosphate cement scaffold (CSPC) with hierarchical pores was developed in this study. The CSPC scaffold with both interconnected macropores on the order of 200-500 μm and micropores of 2-5 μm was synthesized from CPC and calcium silicate (CS) by a NaCl particulate-leaching method. In vitro cell culture with C2C12 model cells, in vivo ectopic bone formation and rabbit femur cavity defect repair were performed to evaluate the osteogeneic capacity of the CSPC/rhBMP-2 scaffold. CPC, CSPC and CPC/rhBMP-2 scaffolds were parallelly investigated for comparison. The results demonstrated that the hierarchical macro/microporous structure, whether in presence of CS or rhBMP-2, highly favored the adhesion of C2C12 cells and bone in-growth into the CPC-based scaffolds. But, in comparison to the CPC-based scaffolds with CS or rhBMP-2 alone, the CSPC/rhBMP-2 scaffold strongly promoted osteogenic differentiation in vitro and osteogenetic efficacy in vivo. Further studies demonstrated that Si ions derived from CSPC contributed mainly to maintain the conformation of rhBMP-2 and thus stimulate the synergistic action of CS and rhBMP-2 in osteogenic differentiation and osteoinductivity. Additionally, the incorporation of CS was also beneficial for the dissolution of the scaffold. Those results suggest that the CSPC has superior properties for incorporation of rhBMP-2 and our developed CSPC/rhBMP-2 scaffold have great potential for future use in bone tissue regeneration.

  18. Predicting bone remodeling around tissue- and bone-level dental implants used in reduced bone width.

    PubMed

    Eser, Atilim; Tonuk, Ergin; Akca, Kivanc; Dard, Michel M; Cehreli, Murat Cavit

    2013-09-03

    The objective of this study was to predict time-dependent bone remodeling around tissue- and bone-level dental implants used in patients with reduced bone width. The remodeling of bone around titanium tissue-level, and titanium and titanium-zirconium alloy bone-level implants was studied under 100 N oblique load for one month by implementing the Stanford theory into three-dimensional finite element models. Maximum principal stress, minimum principal stress, and strain energy density in peri-implant bone and displacement in x- and y- axes of the implant were evaluated. Maximum and minimum principal stresses around tissue-level implant were higher than bone-level implants and both bone-level implants experienced comparable stresses. Total strain energy density in bone around titanium implants slightly decreased during the first two weeks of loading followed by a recovery, and the titanium-zirconium implant showed minor changes in the axial plane. Total strain energy density changes in the loading and contralateral sides were higher in tissue-level implant than other implants in the cortical bone at the horizontal plane. The displacement values of the implants were almost constant over time. Tissue-level implants were associated with higher stresses than bone-level implants. The time-dependent biomechanical outcome of titanium-zirconium alloy bone-level implant was comparable to the titanium implant. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Microgravity Stress: Bone and Connective Tissue.

    PubMed

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

    2016-03-15

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

  20. Super-paramagnetic responsive silk fibroin/chitosan/magnetite scaffolds with tunable pore structures for bone tissue engineering applications.

    PubMed

    Aliramaji, Shamsa; Zamanian, Ali; Mozafari, Masoud

    2017-01-01

    Tissue engineering is a promising approach in repairing damaged tissues. During the last few years, magnetic nanoparticles have been of great interest in this field of study due to their controlled responsive characteristics in specific external magnetic fields. In this study, after synthesizing iron oxide (magnetite) nanoparticles through a reverse coprecipitation method, silk fibroin/chitosan-based magnetic scaffolds were prepared using different amounts of magnetite nanoparticles (0, 0.5, 1 and 2%) by freeze-casting method. The physicochemical activity of the scaffolds was monitored in phosphate-buffered saline (PBS) solution to determine the biodegradation and swelling behaviors. The stability of the magnetite nanoparticles in the fabricated scaffolds was determined by atomic absorption spectroscopy (AAS). Moreover, the cellular activity of the magnetic scaffolds was examined under a static magnetic field. The results showed that the lamellar structured scaffolds having MNPs in the walls could not affect the final structure and deteriorate the biological characteristics of the scaffolds, while the ability of magnetic responsivity was added to the scaffolds. This study warrants further pre-clinical and clinical evaluations. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Interactions between muscle tissues and bone metabolism.

    PubMed

    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. Functional attachment of soft tissues to bone: development, healing, and tissue engineering.

    PubMed

    Lu, Helen H; Thomopoulos, Stavros

    2013-01-01

    Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue-to-bone interface, and concludes with a summary of challenges and future directions.

  3. The effects of collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering.

    PubMed

    Tierney, Claire M; Haugh, Matthew G; Liedl, Jakob; Mulcahy, Fergal; Hayes, Brian; O'Brien, Fergal J

    2009-04-01

    In this study, we examined the effects of varying collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering. Three different collagen contents (0.25%, 0.5% and 1% collagen) and two different dehydrothermal (DHT) crosslinking processes [1] 105 degrees C for 24 h and [2] 150 degrees C for 48 h were investigated. These scaffolds were assessed for (1) pore size, (2) permeability (3) compressive strength and (4) cell viability. The largest pore size, permeability rate, compressive modulus, cell number and cell metabolic activity was all found to occur on the 1% collagen scaffold due to its increased collagen composition and the DHT treatment at 150 degrees C was found to significantly improve the mechanical properties and not to affect cellular number or metabolic activity. These results indicate that doubling the collagen content to 1% and dehydrothermally crosslinking the scaffold at 150 degrees C for 48 h has enhanced mechanical and biological properties of the scaffold making it highly attractive for use in bone tissue engineering.

  4. Shish-kebab-structured poly(ε-caprolactone) nanofibers hierarchically decorated with chitosan-poly(ε-caprolactone) copolymers for bone tissue engineering.

    PubMed

    Jing, Xin; Mi, Hao-Yang; Wang, Xin-Chao; Peng, Xiang-Fang; Turng, Lih-Sheng

    2015-04-01

    In this work, scaffolds with a shish-kebab (SK) structure formed by poly(ε-caprolactone) (PCL) nanofibers and chitosan-PCL (CS-PCL) copolymers were prepared via electrospinning and subsequent crystallization for bone tissue engineering applications. The aim of this study was to introduce nanosized topography and the high biocompatibility of chitosan onto PCL nanofibers to enhance cell affinity to PCL scaffolds. CS-PCL copolymers with various ratios were synthesized, and then spontaneously crystallized as kebabs onto the electrospun PCL fibers, which acted as shishes. Scanning electron microscopy (SEM) results demonstrated that the copolymer with PCL to chitosan ratio of 8.8 could hierarchically decorate the PCL nanofibers and formed well-shaped kebabs on the PCL nanofiber surface. Water contact angle tests and biomimetic activity experiments revealed that the shish-kebab scaffolds with CS-PCL kebabs (PCL-SK(CS-PCL(8.8))) showed enhanced hydrophilicity and mineralization ability compared with smooth PCL and PCL-SK(PCL) shish-kebab scaffolds. Osteoblast-like MG63 cells cultured on the PCL-SK(CS-PCL(8.8)) scaffolds showed optimizing cell attachment, cell viability, and metabolic activity, demonstrating that this kind of scaffold has potential applications in bone tissue engineering.

  5. Interrelationship between bone substitution materials and skeletal muscle tissue.

    PubMed

    Kunert-Keil, Christiane; Botzenhart, Ute; Gedrange, Tomasz; Gredes, Tomasz

    2015-05-01

    Bone density and quantity are primary conditions for the insertion and stability of dental implants. In cases of a lack of adequate maxillary or mandibulary bone, bone augmentation will be necessary. The use of synthetic bioactive bone substitution materials is of increasing importance as alternatives to autogenously bone grafts. It is well known that bone can influence muscle function and muscle function can influence bone structures. Muscles have a considerable potential of adaptation and muscle tissue surrounding an inserted implant or bone surrogate can integrate changes in mechanical load of the muscle and hereupon induce signaling cascades with protein synthesis and arrangement of the cytoskeleton. The Musculus latissimus dorsi is very often used for the analyses of the in vivo biocompatibility of newly designed biomaterials. Beside macroscopically and histologically examination, biocompatibility can be assessed by analyses of the biomaterial influence of gene expression. This review discusses changes in the fiber type distribution, myosin heavy chain isoform composition, histological appearance and vascularization of the skeletal muscle after implantation of bone substitution materials. Especially, the effects of bone surrogates should be described at the molecular-biological and cellular level.

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

    PubMed

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

    2014-10-01

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

  7. Cancellous structure of tarsal bones.

    PubMed Central

    Sinha, D N

    1985-01-01

    The internal structure of the tarsal bones has been studied to investigate their cancellous architecture. It is revealed that these bones have fine and coarse meshworks and even a tendency for obliteration of the trabecular pattern in the bones lying distal to this midtarsal joint. Internal structure of the talus does not show an arched pattern of bony lamellae. An increased density of bony lamellae in the internal structure of the navicular bone could result from excessive stress, enforced by its close relationship to the three cuneiform bones. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:4066465

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

    PubMed Central

    Meka, Archana; Bakthavatchalu, Vasudevan; Sathishkumar, Sabapathi; Lopez, M. Cecilia; Verma, Raj K.; Wallet, Shannon M.; Bhattacharyya, Indraneel; Boyce, Brendan F.; Handfield, Martin; Lamont, Richard J.; Baker, Henry V.; Ebersole, Jeffrey L.; Lakshmyya, Kesavalu N.

    2010-01-01

    Introduction 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. The objectives of this investigation were to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. Methods 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 analyzed for transcript profiles using Murine GeneChip® arrays to provide a molecular profile of the events that occur following infection of these tissues. Results After P. gingivalis infection, 5517 and 1900 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P ≤ 0.05) and up-regulated. Biological pathways significantly impacted by P. gingivalis infection in tissues and calvarial bone included cell adhesion (immune system) molecules, Toll-like receptors, B cell receptor signaling, TGF-β cytokine family receptor signaling, and MHC class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T cell stimulation, and down regulation of antiviral and T cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption. Conclusion This is the first in vivo evidence that localized P. gingivalis infection differentially induces transcription of a broad array of host genes that differed between inflamed soft tissues and calvarial bone. PMID:20331794

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

    PubMed

    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.

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

    PubMed

    Berli, Marcelo; Borau, Carlos; Decco, Oscar; Adams, George; Cook, Richard B; García Aznar, José Manuel; Zioupos, Peter

    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.

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

    PubMed Central

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

    2017-01-01

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

  12. Applications of carbon nanomaterials in bone tissue engineering.

    PubMed

    Venkatesan, Jayachandran; Pallela, Ramjee; Kim, Se-Kwon

    2014-10-01

    In the biomedical field, remarkable advancements have been made in artificial biomaterials for treating bone loss or defects. A variety of synthetic polymers, natural polymers and bioceramics are being used to develop artificial bones. Many natural and synthetic biomaterials, which are being investigated for their physiochemical role in vivo, are currently in the clinical trial stage. Carbon-based prostheses are promising materials that mimic the natural function of bone, e.g., mechanical strength. Recently, carbon-based bone materials, such as carbon nanotubes and graphene, have been widely investigated as potential solutions to several biomedical problems. This review summarizes the biophysicochemical and biomedical properties of carbon nanomaterials composed of polymer and ceramic structures and discusses their functionality in bone tissue engineering.

  13. [The peculiarities of preservation of the soft tissues and bone structures under the conditions of prolonged corpse deposition in the high-latitude cryolitic zone (the island Bely near the Kara Sea coast)].

    PubMed

    Pletyanova, I V

    2016-01-01

    The objective of the present work was the primary forensic medical/medical criminalistic study of exhumed human remains with the determination of the main group characteristics for the purpose of evaluation of the degree of preservation of the soft tissues and bone structures under the conditions of prolonged corpse deposition in the high-latitude cryolitic zone. The materials available for the study consisted of the exhumed remains of 13 corpses. The author describes the transformed features of the soft tissues and bone structures. The former look like a grave wax. It is shown that the peculiar morphological features of the preserved soft tissues and bone structures depend on the burial depth and the characteristic natural factors of the high-latitude cryolitic zone. The main conditions influencing the state of the objects for the forensic medical expertise are considered including prescription of corpse burying, ground properties, freeze/thaw cycles, the influence of sea water, and microbiological factors.

  14. Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

    PubMed Central

    Lu, Helen H.; Thomopoulos, Stavros

    2014-01-01

    Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

  15. The potential impact of bone tissue engineering in the clinic

    PubMed Central

    Mishra, Ruchi; Bishop, Tyler; Valerio, Ian L; Fisher, John P; Dean, David

    2016-01-01

    Bone tissue engineering (BTE) intends to restore structural support for movement and mineral homeostasis, and assist in hematopoiesis and the protective functions of bone in traumatic, degenerative, cancer, or congenital malformation. While much effort has been put into BTE, very little of this research has been translated to the clinic. In this review, we discuss current regenerative medicine and restorative strategies that utilize tissue engineering approaches to address bone defects within a clinical setting. These approaches involve the primary components of tissue engineering: cells, growth factors and biomaterials discussed briefly in light of their clinical relevance. This review also presents upcoming advanced approaches for BTE applications and suggests a probable workpath for translation from the laboratory to the clinic. PMID:27549369

  16. Bone Tissue Engineering with Premineralized Silk Scaffolds

    PubMed Central

    Kim, Hyeon Joo; Kim, Ung-Jin; Kim, Hyun Suk; Li, Chunmei; Wada, Masahisa; Leisk, Gary G.; Kaplan, David L.

    2009-01-01

    Silks fibroin biomaterials are being explored as novel protein-based systems for cell and tissue culture. In the present study, biomimetic growth of calcium phosphate on porous silk fibroin polymeric scaffolds was explored to generate organic/inorganic composites as scaffolds for bone tissue engineering. Aqueous-derived silk fibroin scaffolds were prepared with the addition of polyaspartic acid during processing, followed by the controlled deposition of calcium phosphate by exposure to CaCl2 and Na2HPO4. These mineralized protein-composite scaffolds were subsequently seeded with human bone marrow stem cells (hMSC) and cultured in vitro for 6 weeks under osteogenic conditions with or without BMP-2. The extent of osteoconductivity was assessed by cell numbers, alkaline phosphatase and calcium deposition, along with immunohistochemistry for bone related outcomes. The results suggest increased osteoconductive outcomes with an increase in initial content of apatite and BMP-2 in the silk fibroin porous scaffolds. The premineralization of these highly porous silk fibroin protein scaffolds provided enhanced outcomes for the bone tissue engineering. PMID:18387349

  17. Interconnected porous hydroxyapatite ceramics for bone tissue engineering.

    PubMed

    Yoshikawa, Hideki; Tamai, Noriyuki; Murase, Tsuyoshi; Myoui, Akira

    2009-06-06

    Several porous calcium hydroxyapatite (HA) ceramics have been used clinically as bone substitutes, but most of them possessed few interpore connections, resulting in pathological fracture probably due to poor bone formation within the substitute. We recently developed a fully interconnected porous HA ceramic (IP-CHA) by adopting the 'foam-gel' technique. The IP-CHA had a three-dimensional structure with spherical pores of uniform size (average 150 microm, porosity 75%), which were interconnected by window-like holes (average diameter 40 microm), and also demonstrated adequate compression strength (10-12 MPa). In animal experiments, the IP-CHA showed superior osteoconduction, with the majority of pores filled with newly formed bone. The interconnected porous structure facilitates bone tissue engineering by allowing the introduction of mesenchymal cells, osteotropic agents such as bone morphogenetic protein or vasculature into the pores. Clinically, we have applied the IP-CHA to treat various bony defects in orthopaedic surgery, and radiographic examinations demonstrated that grafted IP-CHA gained radiopacity more quickly than the synthetic HA in clinical use previously. We review the accumulated data on bone tissue engineering using the novel scaffold and on clinical application in the orthopaedic field.

  18. Interconnected porous hydroxyapatite ceramics for bone tissue engineering

    PubMed Central

    Yoshikawa, Hideki; Tamai, Noriyuki; Murase, Tsuyoshi; Myoui, Akira

    2008-01-01

    Several porous calcium hydroxyapatite (HA) ceramics have been used clinically as bone substitutes, but most of them possessed few interpore connections, resulting in pathological fracture probably due to poor bone formation within the substitute. We recently developed a fully interconnected porous HA ceramic (IP-CHA) by adopting the ‘foam-gel’ technique. The IP-CHA had a three-dimensional structure with spherical pores of uniform size (average 150 μm, porosity 75%), which were interconnected by window-like holes (average diameter 40 μm), and also demonstrated adequate compression strength (10–12 MPa). In animal experiments, the IP-CHA showed superior osteoconduction, with the majority of pores filled with newly formed bone. The interconnected porous structure facilitates bone tissue engineering by allowing the introduction of mesenchymal cells, osteotropic agents such as bone morphogenetic protein or vasculature into the pores. Clinically, we have applied the IP-CHA to treat various bony defects in orthopaedic surgery, and radiographic examinations demonstrated that grafted IP-CHA gained radiopacity more quickly than the synthetic HA in clinical use previously. We review the accumulated data on bone tissue engineering using the novel scaffold and on clinical application in the orthopaedic field. PMID:19106069

  19. Template-Mediated Biomineralization for Bone Tissue Engineering.

    PubMed

    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. Microcarriers designed for cell culture and tissue engineering of bone.

    PubMed

    Park, Jeong-Hui; Pérez, Román A; Jin, Guang-Zhen; Choi, Seung-Jun; Kim, Hae-Won; Wall, Ivan B

    2013-04-01

    Microspherical particulates have been an attractive form of biomaterials that find usefulness in cell delivery and tissue engineering. A variety of compositions, including bioactive ceramics, degradable polymers, and their composites, have been developed into a microsphere form and have demonstrated the potential to fill defective bone and to populate tissue cells on curved matrices. To enhance the capacity of cell delivery, the conventional solid form of spheres is engineered to have either a porous structure to hold cells or a thin shell to in-situ encapsulate cells within the structure. Microcarriers can also be a potential reservoir system of bioactive molecules that have therapeutic effects in regulating cell behaviors. Due to their specific form, advanced technologies to culture cell-loaded microcarriers are required, such as simple agitation or shaking, spinner flask, and rotating chamber system. Here, we review systematically, from material design to culture technology, the microspherical carriers used for the delivery of cells and tissue engineering, particularly of bone.

  1. Nanoscale hydroxyapatite particles for bone tissue engineering.

    PubMed

    Zhou, Hongjian; Lee, Jaebeom

    2011-07-01

    Hydroxyapatite (HAp) exhibits excellent biocompatibility with soft tissues such as skin, muscle and gums, making it an ideal candidate for orthopedic and dental implants or components of implants. Synthetic HAp has been widely used in repair of hard tissues, and common uses include bone repair, bone augmentation, as well as coating of implants or acting as fillers in bone or teeth. However, the low mechanical strength of normal HAp ceramics generally restricts its use to low load-bearing applications. Recent advancements in nanoscience and nanotechnology have reignited investigation of nanoscale HAp formation in order to clearly define the small-scale properties of HAp. It has been suggested that nano-HAp may be an ideal biomaterial due to its good biocompatibility and bone integration ability. HAp biomedical material development has benefited significantly from advancements in nanotechnology. This feature article looks afresh at nano-HAp particles, highlighting the importance of size, crystal morphology control, and composites with other inorganic particles for biomedical material development. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress.

    PubMed

    Shadjou, Nasrin; Hasanzadeh, Mohammad

    2015-10-01

    Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone.

  3. Comparison of the data of X-ray microtomography and fluorescence analysis in the study of bone-tissue structure

    NASA Astrophysics Data System (ADS)

    Asadchikov, V. E.; Senin, R. A.; Blagov, A. E.; Buzmakov, A. V.; Gulimova, V. I.; Zolotov, D. A.; Orekhov, A. S.; Osadchaya, A. S.; Podurets, K. M.; Savel'ev, S. V.; Seregin, A. Yu.; Tereshchenko, E. Yu.; Chukalina, M. V.; Kovalchuk, M. V.

    2012-09-01

    The possibility of localizing clusters of heavy atoms is substantiated by comparing the data of X-ray microtomography at different wavelengths, scanning electron microscopy, and X-ray fluorescence analysis. The proximal tail vertebrae of Turner's thick-toed gecko ( Chondrodactylus turneri) have been investigated for the first time by both histological and physical methods, including X-ray microtomography at different wavelengths and elemental analysis. This complex methodology of study made it possible to reveal the regions of accumulation of heavy elements in the aforementioned bones of Turner's thick-toed gecko.

  4. Challenges of bone tissue engineering in orthopaedic patients.

    PubMed

    Guerado, Enrique; Caso, Enrique

    2017-02-18

    Bone defects may impede normal biomechanics and the structural stability of bone as an organ. In many cases, the correction of bone defects requires extensive surgical intervention involving the use of bone-grafting techniques and other procedures in which healing is slow, there is a high risk of infection and considerable pain is provoked - with no guarantee of complete correction of the defect. Therefore, the search for surgical alternatives continues to present a major challenge in orthopaedic traumatology. The reamer-irrigator-aspirator (RIA) system, which was devised to avoid the problems that can arise with autograft harvesting from the iliac crest, consists of collecting the product of the femoral canal after reaming. The RIA technique improves osteogenic differentiation of mesenchymal stem cells, compared to bone marrow aspiration or cancellous bone harvesting from the iliac crest using a spoon. Another approach, the Masquelet technique, consists of reconstructing a long bone defect by means of an induced membrane grown onto an acrylic cement rod inserted to fill the defect; in a second surgical step, once the membrane is constituted, the cement rod is removed and cancellous autograft is used to fill the defect. Both in RIA and in the Masquelet technique, osteosynthesis is usually needed. Bone transportation by compression-distraction lengthening principles is commonly implemented for the treatment of large bone loss. However, complications are frequently encountered with these techniques. Among new techniques that have been proposed to address the problem of large bone loss, the application of stem cells in conjunction with tissue engineering techniques is very promising, as is the creation of personalised medicine (or precision medicine), in which molecular profiling technologies are used to tailor the therapeutic strategy, to ensure the right method is applied for the right person at the right time, after determining the predisposition to disease among

  5. Challenges of bone tissue engineering in orthopaedic patients

    PubMed Central

    Guerado, Enrique; Caso, Enrique

    2017-01-01

    Bone defects may impede normal biomechanics and the structural stability of bone as an organ. In many cases, the correction of bone defects requires extensive surgical intervention involving the use of bone-grafting techniques and other procedures in which healing is slow, there is a high risk of infection and considerable pain is provoked - with no guarantee of complete correction of the defect. Therefore, the search for surgical alternatives continues to present a major challenge in orthopaedic traumatology. The reamer-irrigator-aspirator (RIA) system, which was devised to avoid the problems that can arise with autograft harvesting from the iliac crest, consists of collecting the product of the femoral canal after reaming. The RIA technique improves osteogenic differentiation of mesenchymal stem cells, compared to bone marrow aspiration or cancellous bone harvesting from the iliac crest using a spoon. Another approach, the Masquelet technique, consists of reconstructing a long bone defect by means of an induced membrane grown onto an acrylic cement rod inserted to fill the defect; in a second surgical step, once the membrane is constituted, the cement rod is removed and cancellous autograft is used to fill the defect. Both in RIA and in the Masquelet technique, osteosynthesis is usually needed. Bone transportation by compression-distraction lengthening principles is commonly implemented for the treatment of large bone loss. However, complications are frequently encountered with these techniques. Among new techniques that have been proposed to address the problem of large bone loss, the application of stem cells in conjunction with tissue engineering techniques is very promising, as is the creation of personalised medicine (or precision medicine), in which molecular profiling technologies are used to tailor the therapeutic strategy, to ensure the right method is applied for the right person at the right time, after determining the predisposition to disease among

  6. Enhanced bioactive scaffolds for bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Karnik, Sonali

    Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]. The field of tissue engineering and regenerative medicine involves the use of cells to form a new tissue on bio-absorbable or inert scaffolds. [2, 32] One of the applications of this field is to regenerate the damaged or lost bone by using stem cells or osteoprogenitor cells on scaffolds that can integrate in the host tissue without causing any harmful side effects. [2, 32] A variety of natural, synthetic materials and their combinations have been used to regenerate the damaged bone tissue. [2, 19, 30, 32, 43]. Growth factors have been supplied to progenitor cells to trigger a sequence of metabolic pathways leading to cellular proliferation, differentiation and to enhance their functionality. [56, 57] The challenge persists to supply these proteins, in the range of nano or even picograms, and in a sustained fashion over a period of time. A delivery system has yet to be developed that would mimic the body's inherent mechanism of delivering the growth factor molecules in the required amount to the target organ or tissue. Titanium is the most preferred metal for orthopedic and orthodontic implants. [28, 46, 48] Even though it has better osteogenic properties as compared to other metals and alloys, it still has drawbacks like poor integration into the surrounding host tissue leading to bone resorption and implant failure. [20, 28, 35] It also faces the problem of postsurgical infections that contributes to the implant failure. [26, 37

  7. MRI assessment of bone structure and microarchitecture.

    PubMed

    Chang, Gregory; Boone, Sean; Martel, Dimitri; Rajapakse, Chamith S; Hallyburton, Robert S; Valko, Mitch; Honig, Stephen; Regatte, Ravinder R

    2017-02-06

    Osteoporosis is a disease of weak bone and increased fracture risk caused by low bone mass and microarchitectural deterioration of bone tissue. The standard-of-care test used to diagnose osteoporosis, dual-energy x-ray absorptiometry (DXA) estimation of areal bone mineral density (BMD), has limitations as a tool to identify patients at risk for fracture and as a tool to monitor therapy response. Magnetic resonance imaging (MRI) assessment of bone structure and microarchitecture has been proposed as another method to assess bone quality and fracture risk in vivo. MRI is advantageous because it is noninvasive, does not require ionizing radiation, and can evaluate both cortical and trabecular bone. In this review article, we summarize and discuss research progress on MRI of bone structure and microarchitecture over the last decade, focusing on in vivo translational studies. Single-center, in vivo studies have provided some evidence for the added value of MRI as a biomarker of fracture risk or treatment response. Larger, prospective, multicenter studies are needed in the future to validate the results of these initial translational studies.

  8. Muscle and bone, two interconnected tissues.

    PubMed

    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.

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

    PubMed Central

    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 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 cm2) 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. PMID:26504639

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

    PubMed

    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.

  11. Emerging bone tissue engineering via Polyhydroxyalkanoate (PHA)-based scaffolds.

    PubMed

    Lim, Janice; You, Mingliang; Li, Jian; Li, Zibiao

    2017-10-01

    Polyhydroxyalkanoates (PHAs) are a class of biodegradable polymers derived from microorganisms. On top of their biodegradability and biocompatibility, different PHA types can contribute to varying mechanical and chemical properties. This has led to increasing attention to the use of PHAs in numerous biomedical applications over the past few decades. Bone tissue engineering refers to the regeneration of new bone through providing mechanical support while inducing cell growth on the PHA scaffolds having a porous structure for tissue regeneration. This review first introduces the various properties PHA scaffold that make them suitable for bone tissue engineering such as biocompatibility, biodegradability, mechanical properties as well as vascularization. The typical fabrication techniques of PHA scaffolds including electrospinning, salt-leaching and solution casting are further discussed, followed by the relatively new technology of using 3D printing in PHA scaffold fabrication. Finally, the recent progress of using different types of PHAs scaffold in bone tissue engineering applications are summarized in intrinsic PHA/blends forms or as composites with other polymeric or inorganic hybrid materials. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Bone tissue response to experimental zirconia implants.

    PubMed

    Mihatovic, Ilja; Golubovic, Vladimir; Becker, Jürgen; Schwarz, Frank

    2017-03-01

    This study seeks to assess the bone tissue response at experimental zirconia implants in comparison with titanium implants by means of descriptive histology and histomorphometry in a dog model. Experimental zirconia implants with three different surface roughnesses (Z1 < Z2 < Z3) and conventional sandblasted large grit and acid-etched titanium implants were inserted bilaterally in the lower jaws of nine beagle dogs. Tissue biopsies were obtained after 3 and 14 days and 10 weeks of transmucosal healing. The tissue response was investigated by assessing new, old, and total bone-to-implant contact (nBIC, oBIC, and tBIC). After 3 days, histological specimens of all groups showed an intimate contact between the implant threads and pristine bone (tBIC: Ti 42.3 % > Z2 30.1 % > Z3 28.9 % > Z1 25.1 %, p > 0.05, unpaired t test, respectively). A provisional matrix was evident at all implant surfaces. At 14 days, percentages of BIC increased in all groups (tBIC: Ti 62.1 % > Z3 69.2 % < Z2 44.4 % > Z1 42.3 %; nBIC: Z3 58.9 % > Ti 52.2 % > Z2 35.1 % > Z1 32.5 %). Two implants, one of group Z1 and one of group Z2, were lost. At 10 weeks, 13 of 18 zirconia implants were lost, equally distributed between all three surface modifications. The remaining implants revealed increased BIC values (tBIC: Z3 69.5 % > Ti 58.5 % > Z1 49.7 % > Z2 37.1 %; nBIC: Z3 57.2 % > Ti 46.5 % > Z1 32.3 % > Z2 29.3 %). Histomorphometrical analysis showed comparable mean BIC values in all groups at all healing periods without showing statistical differences (p > 0.05, unpaired t test, respectively). The bone tissue response throughout the healing periods was characterized by a constant bone remodeling accompanied by resorption of old bone in favor of new bone formation at both titanium and zirconia implants. Surface roughness had a positive effect on BIC, although not showing statistical significance. Due to the poor survival rate, the

  13. Patterned silk film scaffolds for aligned lamellar bone tissue engineering

    PubMed Central

    Tien, Lee W.; Gil, Eun Seok; Park, Sang-Hyug; Mandal, Biman B.; Kaplan, David L.

    2013-01-01

    Various porous biomaterial scaffolds have been utilized for bone tissue engineering; however, they are often limited in their ability to replicate the structural hierarchy and mechanics of native cortical bone. In this study, the alignment and osteogenic differentiation of human mesenchymal stem cells (MSCs) on patterned silk films (PF) was investigated as a bottom-up, biomimetic approach toward engineering cortical bone lamellae. Screening films cast with nine different micro and nano scale groove patterns showed that cellular alignment was mediated by an interplay between the width and depth of the patterns. MSCs were differentiated in osteogenic medium for four weeks on the PF that induced the highest degree of alignment, while flat films (FF) served as controls. Gene expression analysis and calcium quantification indicated that the PF supported osteogenic differentiation while also inducing robust lamellar alignment of cells and matrix deposition. A secondary alignment effect was noted on the PF where a new layer of aligned cells grew over the first layer, but rotated obliquely to the underlying pattern direction and first layer orientation. This layering and rotation of the aligned MSCs resembled the characteristic structural organization observed in native lamellar bone. The ability to control multilayered lamellar structural hierarchy from the interplay between a patterned 2D surface and cells suggests intriguing options for future biomaterial scaffolds designed to mimic native tissue structures. PMID:23070941

  14. Preclinical imaging in bone tissue engineering.

    PubMed

    Ventura, Manuela; Boerman, Otto C; de Korte, Chris; Rijpkema, Mark; Heerschap, Arend; Oosterwijk, Egbert; Jansen, John A; Walboomers, X Frank

    2014-12-01

    Since X-rays were discovered, in 1895, and since the first radiological image of a hand, bone tissue has been the subject of detailed medical imaging. However, advances in bone engineering, including the increased complexity of implant scaffolds, currently also underline the limits of X-ray imaging. Therefore, advanced follow-up imaging methods are pivotal to develop. The field of noninvasive, high-sensitivity, and high-resolution anatomical and functional imaging techniques (optical, ultrasound, positron emission tomography, single-photon emission computed tomography, magnetic resonance, etc.) offers a wide variety of tools that potentially could be considered as alternatives, or at least supportive, to the most commonly used X-ray computed tomography. Moreover, dedicated preclinical scanners have become available, with sensitivity and resolution even higher than clinical scanners, thus favoring a quick translation from preclinical to clinical applications. Furthermore, the armamentarium of bone-specific probes and contrast agents for each of this imaging modalities is constantly growing. This review focuses on such preclinical imaging tools, each with its respective strengths and weaknesses, used alone or in combination. Especially, multimodal imaging will dramatically contribute to improve the knowledge on bone healing regenerative processes.

  15. Biomimetic nanoclay scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Ambre, Avinash Harishchandra

    Tissue engineering offers a significant potential alternative to conventional methods for rectifying tissue defects by evoking natural regeneration process via interactions between cells and 3D porous scaffolds. Imparting adequate mechanical properties to biodegradable scaffolds for bone tissue engineering is an important challenge and extends from molecular to macroscale. This work focuses on the use of sodium montmorillonite (Na-MMT) to design polymer composite scaffolds having enhanced mechanical properties along with multiple interdependent properties. Materials design beginning at the molecular level was used in which Na-MMT clay was modified with three different unnatural amino acids and further characterized using Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD). Based on improved bicompatibility with human osteoblasts (bone cells) and intermediate increase in d-spacing of MMT clay (shown by XRD), 5-aminovaleric acid modified clay was further used to prepare biopolymer (chitosan-polygalacturonic acid complex) scaffolds. Osteoblast proliferation in biopolymer scaffolds containing 5-aminovaleric acid modified clay was similar to biopolymer scaffolds containing hydroxyapatite (HAP). A novel process based on biomineralization in bone was designed to prepare 5-aminovaleric acid modified clay capable of imparting multiple properties to the scaffolds. Bone-like apatite was mineralized in modified clay and a novel nanoclay-HAP hybrid (in situ HAPclay) was obtained. FTIR spectroscopy indicated a molecular level organic-inorganic association between the intercalated 5-aminovaleric acid and mineralized HAP. Osteoblasts formed clusters on biopolymer composite films prepared with different weight percent compositions of in situ HAPclay. Human MSCs formed mineralized nodules on composite films and mineralized extracellular matrix (ECM) in composite scaffolds without the use of osteogenic supplements. Polycaprolactone (PCL), a synthetic polymer, was

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

    PubMed Central

    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

  17. Water-mediated structuring of bone apatite.

    PubMed

    Wang, Yan; Von Euw, Stanislas; Fernandes, Francisco M; Cassaignon, Sophie; Selmane, Mohamed; Laurent, Guillaume; Pehau-Arnaudet, Gérard; Coelho, Cristina; Bonhomme-Coury, Laure; Giraud-Guille, Marie-Madeleine; Babonneau, Florence; Azaïs, Thierry; Nassif, Nadine

    2013-12-01

    It is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite. This disordered layer is reminiscent of those found around the crystalline core of calcified biominerals in various natural composite materials in vivo. This work provides an extended local model of bone biomineralization.

  18. The current state of bone and tissue banking in Australia.

    PubMed

    Morgan, D A; Ilyas, I; Bryce, S L; Johnson, N

    1998-01-01

    The development of bone and tissue banking in Australia over the last decade is described and details of the administrative structure, donor and recipient testing protocols, allograft segment processing procedures, and internal audit safety arrangements are also provided. Demographic data concerning both the retrieval and dispersal of musculoskeletal allograft materials in Australia are also discussed. Current price schedules for a variety of allograft materials available in Australia are made available for international comparison.

  19. 3D conductive nanocomposite scaffold for bone tissue engineering.

    PubMed

    Shahini, Aref; Yazdimamaghani, Mostafa; Walker, Kenneth J; Eastman, Margaret A; Hatami-Marbini, Hamed; Smith, Brenda J; Ricci, John L; Madihally, Sundar V; Vashaee, Daryoosh; Tayebi, Lobat

    2014-01-01

    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 microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli.

  20. 3D conductive nanocomposite scaffold for bone tissue engineering

    PubMed Central

    Shahini, Aref; Yazdimamaghani, Mostafa; Walker, Kenneth J; Eastman, Margaret A; Hatami-Marbini, Hamed; Smith, Brenda J; Ricci, John L; Madihally, Sundar V; Vashaee, Daryoosh; Tayebi, Lobat

    2014-01-01

    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 microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli. PMID:24399874

  1. Exercise and Regulation of Bone and Collagen Tissue Biology.

    PubMed

    Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja; Magnusson, S Peter

    2015-01-01

    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 anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. In contrast to tissue responses with exercise, lack of mechanical tissue loading through inactivity or immobilization of the human body will result in a dramatic loss of connective tissue content, structure, 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 and exercise. © 2015 Elsevier Inc. All rights reserved.

  2. Imaging of Alkaline Phosphatase Activity in Bone Tissue

    PubMed Central

    Gade, Terence P.; Motley, Matthew W.; Beattie, Bradley J.; Bhakta, Roshni; Boskey, Adele L.; Koutcher, Jason A.; Mayer-Kuckuk, Philipp

    2011-01-01

    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. PMID:21799916

  3. New method for the fabrication of highly osteoconductive β-1,3-glucan/HA scaffold for bone tissue engineering: Structural, mechanical, and biological characterization.

    PubMed

    Klimek, Katarzyna; Przekora, Agata; Pałka, Krzysztof; Ginalska, Grażyna

    2016-10-01

    Recent studies have shown that thermal method for β-1,3-glucan (curdlan) gelation performed at temperature above 80°C enables fabrication of biocompatible bone scaffolds. The aim of this study was to establish new method for fabrication of β-1,3-glucan/hydroxyapatite (glu/HA) scaffold using ion-exchanging dialysis for curdlan gelation that allows for the modifications of the glu/HA material with thermo-sensitive agents like growth factors or adhesive proteins. Obtained results reveal that fabricated scaffold appears to be highly osteoconductive as it is nontoxic, promotes osteoblast growth and proliferation as well as increases bone alkaline phosphatase level thereby enhancing cell differentiation. It was demonstrated that developed new method for the glu/HA scaffold fabrication allows to obtain material that not only can be modified with thermo-sensitive agents at the stage of production process but also is a promising candidate for bone tissue engineering applications to act as a framework for osteoblasts to spread and form new bone. It should be noted that dialysis method for curdlan gelation has never been used before to fabricate bone scaffold. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2528-2536, 2016. © 2016 Wiley Periodicals, Inc.

  4. Bone hierarchical structure in three dimensions.

    PubMed

    Reznikov, Natalie; Shahar, Ron; Weiner, Steve

    2014-09-01

    Bone is a complex hierarchically structured family of materials that includes a network of cells and their interconnected cell processes. New insights into the 3-D structure of various bone materials (mainly rat and human lamellar bone and minipig fibrolamellar bone) were obtained using a focused ion beam electron microscope and the serial surface view method. These studies revealed the presence of two different materials, the major material being the well-known ordered arrays of mineralized collagen fibrils and associated macromolecules, and the minor component being a relatively disordered material composed of individual collagen fibrils with no preferred orientation, with crystals inside and possibly between fibrils, and extensive ground mass. Significantly, the canaliculi and their cell processes are confined within the disordered material. Here we present a new hierarchical scheme for several bone tissue types that incorporates these two materials. The new scheme updates the hierarchical scheme presented by Weiner and Wagner (1998). We discuss the structures at different hierarchical levels with the aim of obtaining further insights into structure-function-related questions, as well as defining some remaining unanswered questions.

  5. Development of porous scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Ramay, Hassna Rehman

    In bone tissue engineering, biodegradable scaffolds are used as a temporary biological and mechanical support for new tissue growth. A scaffold must have good biocompatibility, controllable degradation rate, and enough mechanical strength to support bone cell attachment, differentiation, and proliferation as it gradually degrades and finally is completely replaced by new bone tissues. Biological studies and clinical practices have established that a three-dimensional interconnected porous structure is necessary to allow cell attachment, proliferation, and differentiation, and to provide pathways for biofluids. However, the mechanical strength of a material generally decreases as increasing porosity. The conflicting interests between biological and mechanical requirements thus pose a challenge in developing porous scaffolds for load-bearing bone tissue engineering. Two types of ceramic scaffolds, (1) Hydroxaypatite and (2) Hydroxaypatite/tricalcium phosphate, are prepared in this study utilizing a novel technique that combines the gel casting and polymer sponge methods. This technique provides better control over material microstructure and can produce scaffolds with enhanced mechanical toughness and strength. The hydroxyapatite scaffolds prepared by this technique have an open, uniform and interconnected porous structure (˜porosity = 76%) with compressive modulus of 7 GPa, comparable to that of cortical bone, and compressive strength of 5 MPa, comparable to that of cancellous bone. The second type of ceramic scaffold is a biphasic nano composite with tricalcium phosphate as the main matrix reinforced with hydroxyapatite (HA) nano-fibers. The porous scaffold attained a compressive strength of 9.6 MPa (˜porosity = 73%), comparable to the high-end value of cancellous bone. The toughness of the scaffold increased from 1.00 to 1.72 kN/m (˜porosity = 73%), as the addition of HA nano-fibers increased up to 5 wt.%. Polymer scaffolds are prepared using a solid

  6. Autocorrelation analysis of bone structure.

    PubMed

    Rotter, M; Berg, A; Langenberger, H; Grampp, S; Imhof, H; Moser, E

    2001-07-01

    We propose a method called spatial autocorrelation analysis (SACA) to determine the spatial anisotropy of the trabecular bone in order to investigate osteoporosis. For demonstrating the potential of SACA we first evaluate the method on rectangular, simulated test patterns as a simple model for the anisotropic pore structure of the bone. As a next step towards biomedical application, photographic reference images of human vertebral bone were investigated by SACA. Osteoporotic bone structure could be clearly differentiated from non-osteoporotic sample images. Moreover, for demonstration of the applicability and potential of the method for in vivo characterization of osteoporosis, the microstructure of the human calcaneus was investigated by MR-microimaging on a young healthy male subject and an osteoporotic female. The measurements were performed using a high-field (3T) whole-body MR tomograph equipped with a special, strong head gradient system. The signal was acquired with a surface coil mounted on an in-house-built device for convenient immobilization of the subject's foot. Using a 3D gradient echo sequence a resolution of 0.254 x 0.254 x 2.188 mm3 was achieved in vivo. Selected images were inverted, gradient corrected for the inhomogeneous but sensitive detection by the surface coil, and subsequently analyzed by SACA. The anisotropy of bone structure detected by SACA is a possible candidate for noninvasive determination of the osteoporotic status, potentially complementing standard bone mineral density measurements. Copyright 2001 Wiley-Liss, Inc.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Shadjou, Nasrin; Hasanzadeh, Mohammad

    2016-05-01

    Tissue engineering and regenerative medicine represent areas of increasing interest because of the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Graphene and its derivatives have attracted much interest for applications in bone tissue engineering. For this purpose, this review focuses on more recent advances in tissue engineering based on graphene-biomaterials from 2013 to May 2015. The purpose of this article was to give a general description of studies of nanostructured graphene derivatives for bone tissue engineering. In this review, we highlight how graphene family nanomaterials are being exploited for bone tissue engineering. Firstly, the main requirements for bone tissue engineering were discussed. Then, the mechanism by which graphene based materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. In addition, graphene-based bioactive glass, as a potential drug/growth factor carrier, was reviewed which includes the composition-structure-drug delivery relationship and the functional effect on the tissue-stimulation properties. Also, the effect of structural and textural properties of graphene based materials on development of new biomaterials for production of bone implants and bone cements were discussed. Finally, the present review intends to provide the reader an overview of the current state of the graphene based biomaterials in bone tissue engineering, its limitations and hopes as well as the future research trends for this exciting field of science. © 2016 Wiley Periodicals, Inc.

  9. Vascularised endosteal bone tissue in armoured sauropod dinosaurs

    PubMed Central

    Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

    2016-01-01

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

  10. Vascularised endosteal bone tissue in armoured sauropod dinosaurs.

    PubMed

    Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

    2016-04-26

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

  11. Erythropoietin modulates the structure of bone morphogenetic protein 2-engineered cranial bone.

    PubMed

    Sun, Hongli; Jung, Younghun; Shiozawa, Yusuke; Taichman, Russell S; Krebsbach, Paul H

    2012-10-01

    The ideally engineered bone should have similar structural and functional properties to the native tissue. Although structural integrity is critical for functional bone regeneration, we know less about modulating the structural properties of the engineered bone elicited by bone morphogenetic protein (BMP) than efficacy and safety. Erythropoietin (Epo), a primary erythropoietic hormone, has been used to augment blood transfusion in orthopedic surgery. However, the effects of Epo on bone regeneration are not well known. Here, we determined the role of Epo in BMP2-induced bone regeneration using a cranial defect model. Epo administration improved the quality of BMP2-induced bone and more closely resembled natural cranial bone with a higher bone volume (BV) fraction and lower marrow fraction when compared with BMP2 treatment alone. Epo increased red blood cells (RBCs) in peripheral blood and also increased hematopoietic and mesenchymal stem cell (MSC) populations in bone marrow. Consistent with our previous work, Epo increased osteoclastogenesis both in vitro and in vivo. Results from a metatarsal organ culture assay suggested that Epo-promoted osteoclastogenesis contributed to angiogenesis because angiogenesis was blunted when osteoclastogenesis was blocked by alendronate (ALN) or osteoprotegerin (OPG). Earlier calcification of BMP2-induced temporary chondroid tissue was observed in the Epo+BMP group compared to BMP2 alone. We conclude that Epo significantly enhanced the outcomes of BMP2-induced cranial bone regeneration in part through its actions on osteoclastogenesis and angiogenesis.

  12. Mechanical basis of bone strength: influence of bone material, bone structure and muscle action

    PubMed Central

    Hart, N.H.; Nimphius, S.; Rantalainen, T.; Ireland, A.; Siafarikas, A.; Newton, R.U.

    2017-01-01

    This review summarises current understanding of how bone is sculpted through adaptive processes, designed to meet the mechanical challenges it faces in everyday life and athletic pursuits, serving as an update for clinicians, researchers and physical therapists. Bone’s ability to resist fracture under the large muscle and locomotory forces it experiences during movement and in falls or collisions is dependent on its established mechanical properties, determined by bone’s complex and multidimensional material and structural organisation. At all levels, bone is highly adaptive to habitual loading, regulating its structure according to components of its loading regime and mechanical environment, inclusive of strain magnitude, rate, frequency, distribution and deformation mode. Indeed, the greatest forces habitually applied to bone arise from muscular contractions, and the past two decades have seen substantial advances in our understanding of how these forces shape bone throughout life. Herein, we also highlight the limitations of in vivo methods to assess and understand bone collagen, and bone mineral at the material or tissue level. The inability to easily measure or closely regulate applied strain in humans is identified, limiting the translation of animal studies to human populations, and our exploration of how components of mechanical loading regimes influence mechanoadaptation. PMID:28860414

  13. Effect of the deformation rate on the nature of compound bone tissue fracture

    NASA Astrophysics Data System (ADS)

    Melnis, A. É.

    1983-01-01

    An electron microscopic study showed that the major type of fracture of moist bone tissue is viscous fracture with the extrusion of elements on various structural levels. Larger elements are found at lower deformation rates, and finer elements are found at higher ɛ11. The longitudinal shear deformation between the osteons and interosteon ground substance, between the individual lamellae in the osteons, between the collagen-mineral fibers and interfibrillar ground substance, and between hydroxyapatite crystals and collagen molecules largely accounts for the viscoelastic properties of bone tissue. Processes occurring on some structural level of bone tissue predominate at certain specific deformation rates.

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

    SciTech Connect

    Campi, G.; Pezzotti, G.; Fratini, M.; Ricci, A.; Burghammer, M.; Cancedda, R.; Mastrogiacomo, M.; Bukreeva, I.; Cedola, A.

    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.

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

    NASA Astrophysics Data System (ADS)

    Campi, G.; Pezzotti, G.; Fratini, M.; Ricci, A.; Burghammer, M.; Cancedda, R.; Mastrogiacomo, M.; Bukreeva, I.; Cedola, A.

    2013-12-01

    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.

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

    PubMed Central

    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. PMID:27781021

  17. Thermal stabilization of collagen molecules in bone tissue.

    PubMed

    Trebacz, Hanna; Wójtowicz, Krzysztof

    2005-12-30

    Differential thermal calorimetry (DSC) analysis of partially dehydrated bovine bone, demineralized bone and bovine tendon collagen was performed up to 300 degrees C to determine factors influencing stability of mineralized collagen in bone tissue. Two endothermal regions were recognized. The first, attributed to denaturation of collagen triple helix, was hydration dependent and had a peak at 155-165 degrees C in bone, 118-137 degrees C in tendon and 131-136 degrees C in demineralized bone. The second region extended from 245 to 290 degrees C in bone and from 200 to 280 degrees C in tendon and was connected with melting and decomposition of collagen. Differences in thermodynamic parameters between cortical and trabecular bone tissue were stated. Activation energy of collagen unfolding in native bone tissue increased with dehydration of the bone. From the results of the present study we conclude that dehydrated bone collagen is thermally very stable both in native and in demineralized bone. Presence of mineral additionally stabilizes bone tissue.

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

    PubMed

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

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

  19. Rapid prototyping technology and its application in bone tissue engineering*

    PubMed Central

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

    2017-01-01

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

  20. Tissue Engineered Bone Grafts: Biological Requirements, Tissue Culture and Clinical Relevance

    PubMed Central

    Fröhlich, Mirjam; Grayson, Warren L.; Wan, Leo Q.; Marolt, Darja; Drobnic, Matej; Vunjak-Novakovic, Gordana

    2009-01-01

    The tremendous need for bone tissue in numerous clinical situations and the limited availability of suitable bone grafts are driving the development of tissue engineering approaches to bone repair. In order to engineer viable bone grafts, one needs to understand the mechanisms of native bone development and fracture healing, as these processes should ideally guide the selection of optimal conditions for tissue culture and implantation. Engineered bone grafts have been shown to have capacity for osteogenesis, osteoconduction, osteoinduction and osteointegration - functional connection between the host bone and the graft. Cells from various anatomical sources in conjunction with scaffolds and osteogenic factors have been shown to form bone tissue in vitro. The use of bioreactor systems to culture cells on scaffolds before implantation further improved the quality of the resulting bone grafts. Animal studies confirmed the capability of engineered grafts to form bone and integrate with the host tissues. However, the vascularization of bone remains one of the hurdles that need to be overcome if clinically sized, fully viable bone grafts are to be engineered and implanted. We discuss here the biological guidelines for tissue engineering of bone, the bioreactor cultivation of human mesenchymal stem cells on three-dimensional scaffolds, and the need for vascularization and functional integration of bone grafts following implantation. PMID:19075755

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Tissue Engineering Strategies for the Tendon/ligament-to-bone insertion

    PubMed Central

    Smith, Lester; Xia, Younan; Galatz, Leesa M.; Genin, Guy M.; Thomopoulos, Stavros

    2012-01-01

    Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require re-attachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of re-injury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations. PMID:22185608

  3. Tissue-engineering strategies for the tendon/ligament-to-bone insertion.

    PubMed

    Smith, Lester; Xia, Younan; Galatz, Leesa M; Genin, Guy M; Thomopoulos, Stavros

    2012-01-01

    Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require reattachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of reinjury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations.

  4. Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering.

    PubMed

    Won, Jong-Eun; Yun, Ye-Rang; Jang, Jun-Hyeog; Yang, Sung-Hee; Kim, Joong-Hyun; Chrzanowski, Wojciech; Wall, Ivan B; Knowles, Jonathan C; Kim, Hae-Won

    2015-07-01

    Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.

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

    PubMed Central

    Gerhardt, Lutz-Christian; Boccaccini, Aldo R.

    2010-01-01

    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. PMID:28883315

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

    PubMed

    Lu, Helen H; Spalazzi, Jeffrey P

    2009-07-01

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

  7. Recent Developments of Functional Scaffolds for Craniomaxillofacial Bone Tissue Engineering Applications

    PubMed Central

    Kinoshita, Yukihiko; Maeda, Hatsuhiko

    2013-01-01

    Autogenous bone grafting remains a gold standard for the reconstruction critical-sized bone defects in the craniomaxillofacial region. Nevertheless, this graft procedure has several disadvantages such as restricted availability, donor-site morbidity, and limitations in regard to fully restoring the complicated three-dimensional structures in the craniomaxillofacial bone. The ultimate goal of craniomaxillofacial bone reconstruction is the regeneration of the physiological bone that simultaneously fulfills both morphological and functional restorations. Developments of tissue engineering in the last two decades have brought such a goal closer to reality. In bone tissue engineering, the scaffolds are fundamental, elemental and mesenchymal stem cells/osteoprogenitor cells and bioactive factors. A variety of scaffolds have been developed and used as spacemakers, biodegradable bone substitutes for transplanting to the new bone, matrices of drug delivery system, or supporting structures enhancing adhesion, proliferation, and matrix production of seeded cells according to the circumstances of the bone defects. However, scaffolds to be clinically completely satisfied have not been developed yet. Development of more functional scaffolds is required to be applied widely to cranio-maxillofacial bone defects. This paper reviews recent trends of scaffolds for crania-maxillofacial bone tissue engineering, including our studies. PMID:24163634

  8. Fully automated localization of multiple pelvic bone structures on MRI.

    PubMed

    Onal, Sinan; Lai-Yuen, Susana; Bao, Paul; Weitzenfeld, Alfredo; Hart, Stuart

    2014-01-01

    In this paper, we present a fully automated localization method for multiple pelvic bone structures on magnetic resonance images (MRI). Pelvic bone structures are currently identified manually on MRI to identify reference points for measurement and evaluation of pelvic organ prolapse (POP). Given that this is a time-consuming and subjective procedure, there is a need to localize pelvic bone structures without any user interaction. However, bone structures are not easily differentiable from soft tissue on MRI as their pixel intensities tend to be very similar. In this research, we present a model that automatically identifies the bounding boxes of the bone structures on MRI using support vector machines (SVM) based classification and non-linear regression model that captures global and local information. Based on the relative locations of pelvic bones and organs, and local information such as texture features, the model identifies the location of the pelvic bone structures by establishing the association between their locations. Results show that the proposed method is able to locate the bone structures of interest accurately. The pubic bone, sacral promontory, and coccyx were correctly detected (DSI > 0.75) in 92%, 90%, and 88% of the testing images. This research aims to enable accurate, consistent and fully automated identification of pelvic bone structures on MRI to facilitate and improve the diagnosis of female pelvic organ prolapse.

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

    NASA Astrophysics Data System (ADS)

    Yu, Sungkon; Jang, Seulki; Lee, Sangyeob; Park, Jihoon; Ha, Myungjin; Radfar, Edalat; Jung, Byungjo

    2016-03-01

    This study investigates the feasibility of an endoscopic laser speckle imaging modality (ELSIM) in the measurement of perfusion of flowing fluid in optical bone tissue phantom(OBTP). Many studies suggested that the change of cochlear blood flow was correlated with auditory disorder. Cochlear microcirculation occurs under the 200μm thickness bone which is the part of the internal structure of the temporal bone. Concern has been raised regarding of getting correct optical signal from hard tissue. In order to determine the possibility of the measurement of cochlear blood flow under bone tissue using the ELSIM, optical tissue phantom (OTP) mimicking optical properties of temporal bone was applied.

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

    PubMed

    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.

  11. Cartilage, bone, and intermandibular connective tissue in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi).

    PubMed

    Kemp, Anne

    2013-10-01

    The connective tissue that links the bones of the mandible in the Australian lungfish, Neoceratodus forsteri, has been described as an intermandibular cartilage, and as such has been considered important for phylogenetic analyses among lower vertebrates. However, light and electron microscopy of developing lungfish jaws demonstrates that the intermandibular tissue, like the connective tissue that links the bones of the upper jaw, contains fibroblasts and numerous bundles of collagen fibrils, extending from the trabeculae of the bones supporting the tooth plates. It differs significantly in structure and in staining reactions from the cartilage and the bone found in this species. In common with the cladistian Polypterus and with actinopterygians and some amphibians, lungfish have no intermandibular cartilage. The connective tissue linking the mandibular bones has no phylogenetic significance for systematic grouping of lungfish, as it is present in a range of different groups among lower vertebrates. Copyright © 2013 Wiley Periodicals, Inc.

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

    PubMed

    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.

  13. Injectable hydrogels for cartilage and bone tissue engineering

    PubMed Central

    Liu, Mei; Zeng, Xin; Ma, Chao; Yi, Huan; Ali, Zeeshan; Mou, Xianbo; Li, Song; Deng, Yan; He, Nongyue

    2017-01-01

    Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed. PMID:28584674

  14. In vitro simulation of pathological bone conditions to predict clinical outcome of bone tissue engineered materials

    NASA Astrophysics Data System (ADS)

    Nguyen, Duong Thuy Thi

    According to the Centers for Disease Control, the geriatric population of ≥65 years of age will increase to 51.5 million in 2020; 40% of white women and 13% of white men will be at risk for fragility fractures or fractures sustained under normal stress and loading conditions due to bone disease, leading to hospitalization and surgical treatment. Fracture management strategies can be divided into pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, and non-unions. Compromised innate bone healing reactions of patients with bone diseases are exacerbated with protective bone therapy. Once these patients sustain a fracture, bone healing is a challenge, especially when fracture stabilization is unsuccessful. Traditional stabilizing screw and plate systems were designed with emphasis on bone mechanics rather than biology. Bone grafts are often used with fixation devices to provide skeletal continuity at the fracture gap. Current bone grafts include autologous bone tissue and donor bone tissue; however, the quality and quantity demanded by fragility fractures sustained by high-risk geriatric patients and patients with bone diseases are not met. Consequently, bone tissue engineering strategies are advancing towards functionalized bone substitutes to provide fracture reconstruction while effectively mediating bone healing in normal and diseased fracture environments. In order to target fragility fractures, fracture management strategies should be tailored to allow bone regeneration and fracture stabilization with bioactive bone substitutes designed for the pathological environment. The clinical outcome of these materials must be predictable within various disease environments. Initial development of a targeted

  15. Bone tissue heating and ablation by short and ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Letfullin, Renat R.; Rice, Colin E. W.; George, Thomas F.

    2010-02-01

    Biological hard tissues, such as those found in bone and teeth, are complex tissues that build a strong mineral structure over an organic matrix framework. The laser-matter interaction for bone hard tissues holds great interest to laser surgery and laser dentistry; the use of short/ultrashort pulses, in particular, shows interesting behaviors not seen in continuous wave lasers. High laser energy densities in ultrashort pulses can be focused on a small irradiated surface (spot diameter is 10-50 μm) leading to rapid temperature rise and thermal ablation of the bone tissue. Ultrashort pulses, specifically those in the picosecond and femtosecond ranges, impose several challenges in modeling bone tissue response. In the present paper we perform time-dependent thermal simulations of short and ultrashort pulse laser-bone interactions in singlepulse and multipulse (set of ultrashort pulses) modes of laser heating. A comparative analysis for both radiation modes is discussed for laser heating of different types of the solid bone on the nanosecond, picosecond and femtosecond time scales. It is shown that ultrashort laser pulses with high energy densities can ablate bone tissue without heating tissues bordering the ablation creator. This reaction is particularly desirable as heat accumulation and thermal damage are the main factors affecting tissue regrowth rates, and thus patient recovery times.

  16. [Interaction between myeloma cells and bone tissue].

    PubMed

    Seckinger, A; Hose, D

    2014-06-01

    Multiple myeloma is the malignant disease which most frequently leads to bone lesions. Approximately 80% of myeloma patients develop osteoporosis, lytic bone lesions (osteolysis) or fractures during the course of the disease. Of these patients 43% suffer pathological fractures most often of the vertebrae followed by fractures of the long bones. The methods used in the described articles include, e.g. gene expression profiling, enzyme-linked immunosorbent assays and radiological techniques. Myeloma bone disease represents a threefold therapeutic problem: (i) per se because of the associated morbidity, mortality and the accompanying decrease of quality of life, (ii) as survival space for (residual) myeloma cells after primarily successful chemotherapy and subsequently necessary chemotherapeutic treatment, and (iii) the occurrence of bone lesions in asymptomatic patients is the most common cause for the initiation of treatment to avoid myeloma-induced fractures. Myeloma cells harbor a high median number of chromosomal aberrations and multiple changes in gene expression compared to normal bone marrow plasma cells leading to the aberrant production of survival, proliferation, pro-angiogenic and bone turnover influencing factors or the induction of those factors in the bone marrow microenvironment. This causes an imbalanced bone turnover in the sense of an increased number and activity of osteoclasts while bone formation by osteoblasts is almost completely suspended. Therapeutic approaches, systemically and locally therefore aim at stimulation of osteoblasts and inhibition of bone resorption.

  17. Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges.

    PubMed

    Orciani, Monia; Fini, Milena; Di Primio, Roberto; Mattioli-Belmonte, Monica

    2017-01-01

    The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis.

  18. Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges

    PubMed Central

    Orciani, Monia; Fini, Milena; Di Primio, Roberto; Mattioli-Belmonte, Monica

    2017-01-01

    The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis. PMID:28386538

  19. Bone tissue engineering and regenerative medicine: targeting pathological fractures.

    PubMed

    Nguyen, Duong T; Burg, Karen J L

    2015-01-01

    Patients with bone diseases have the highest risk of sustaining fractures and of suffering from nonunion bone healing due to tissue degeneration. Current fracture management strategies are limited in design and functionality and do not effectively promote bone healing within a diseased bone environment. Fracture management approaches include pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, and nonunions. To target fragility fractures, fracture management strategies should include bioactive bone substitutes designed for the pathological environment. However, the clinical outcome of these materials must be predictable within various disease environments. Initial development of a targeted treatment strategy should focus on simulating the physiological in vitro bone environment to predict clinical effectiveness of the engineered bone. An in vitro test system can facilitate reduction of implant failures and non-unions in fragility fractures.

  20. Scaffold curvature-mediated novel biomineralization process originates a continuous soft tissue-to-bone interface.

    PubMed

    Paris, Michael; Götz, Andreas; Hettrich, Inga; Bidan, Cécile M; Dunlop, John W C; Razi, Hajar; Zizak, Ivo; Hutmacher, Dietmar W; Fratzl, Peter; Duda, Georg N; Wagermaier, Wolfgang; Cipitria, Amaia

    2017-09-15

    A myriad of shapes are found in biological tissues, often naturally evolved to fulfill a particular function. In the field of tissue engineering, substrate geometry influences cell behavior and tissue formation in vitro, yet little is known how this translates to an in vivo scenario. Here we investigate scaffold curvature-induced tissue growth, without additional growth factors or cells, in an ovine animal model. We show that soft tissue formation follows a curvature-driven tissue growth model. The highly organized endogenous soft matrix, potentially under mechanical strain, leads to a non-standard form of biomineralization, whereby the pre-existing organic matrix is mineralized without collagen remodeling and without an intermediate cartilage ossification phase. Micro- and nanoscale characterization of the tissue microstructure using histology, backscattered electron (BSE) and second-harmonic generation (SHG) imaging and synchrotron small angle X-ray scattering (SAXS) revealed (i) continuous collagen fibers across the soft-hard tissue interface on the tip of mineralized cones, and (ii) bone remodeling by basic multicellular units (BMUs) in regions adjacent to the native cortical bone. Thus, features of soft tissue-to-bone interface resembling the insertion sites of ligaments and tendons into bone were created, using a scaffold that did not mimic the structural or biological gradients across such a complex interface at its mature state. This study provides fundamental knowledge for biomimetic scaffold design in the fields of bone regeneration and soft tissue-to-bone interface tissue engineering. Geometry influences cell behavior and tissue formation in vitro. However, little is known how this translates to an in vivo scenario. Here we investigate the influence of scaffold mean surface curvature on in vivo tissue growth using an ovine animal model. Based on a multiscale tissue microstructure characterization, we show a seamless integration of soft tissue into newly

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

    PubMed

    Harsanyl, L

    1977-02-01

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

  2. Measurement of guided mode wavenumbers in soft tissue-bone mimicking phantoms using ultrasonic axial transmission

    NASA Astrophysics Data System (ADS)

    Chen, Jiangang; Foiret, Josquin; Minonzio, Jean-Gabriel; Talmant, Maryline; Su, Zhongqing; Cheng, Li; Laugier, Pascal

    2012-05-01

    Human soft tissue is an important factor that influences the assessment of human long bones using quantitative ultrasound techniques. To investigate such influence, a series of soft tissue-bone phantoms (a bone-mimicking plate coated with a layer of water, glycerol or silicon rubber) were ultrasonically investigated using a probe with multi-emitter and multi-receiver arrays in an axial transmission configuration. A singular value decomposition signal processing technique was applied to extract the frequency-dependent wavenumbers of several guided modes. The results indicate that the presence of a soft tissue-mimicking layer introduces additional guided modes predicted by a fluid waveguide model. The modes propagating in the bone-mimicking plate covered by the soft-tissue phantom are only slightly modified compared to their counterparts in the free bone-mimicking plate, and they are still predicted by an elastic transverse isotropic two-dimensional waveguide. Altogether these observations suggest that the soft tissue-bone phantoms can be modeled as two independent waveguides. Even in the presence of the overlying soft tissue-mimicking layer, the modes propagating in the bone-mimicking plate can still be extracted and identified. These results suggest that our approach can be applied for the purpose of the characterization of the material and structural properties of cortical bone.

  3. Measurement of guided mode wavenumbers in soft tissue-bone mimicking phantoms using ultrasonic axial transmission.

    PubMed

    Chen, Jiangang; Foiret, Josquin; Minonzio, Jean-Gabriel; Talmant, Maryline; Su, Zhongqing; Cheng, Li; Laugier, Pascal

    2012-05-21

    Human soft tissue is an important factor that influences the assessment of human long bones using quantitative ultrasound techniques. To investigate such influence, a series of soft tissue-bone phantoms (a bone-mimicking plate coated with a layer of water, glycerol or silicon rubber) were ultrasonically investigated using a probe with multi-emitter and multi-receiver arrays in an axial transmission configuration. A singular value decomposition signal processing technique was applied to extract the frequency-dependent wavenumbers of several guided modes. The results indicate that the presence of a soft tissue-mimicking layer introduces additional guided modes predicted by a fluid waveguide model. The modes propagating in the bone-mimicking plate covered by the soft-tissue phantom are only slightly modified compared to their counterparts in the free bone-mimicking plate, and they are still predicted by an elastic transverse isotropic two-dimensional waveguide. Altogether these observations suggest that the soft tissue-bone phantoms can be modeled as two independent waveguides. Even in the presence of the overlying soft tissue-mimicking layer, the modes propagating in the bone-mimicking plate can still be extracted and identified. These results suggest that our approach can be applied for the purpose of the characterization of the material and structural properties of cortical bone.

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

    PubMed

    Ruggiu, Alessandra; Cancedda, Ranieri

    2015-12-01

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

  5. The influence of follistatin on mechanical properties of bone tissue in growing mice with overexpression of follistatin.

    PubMed

    Gajos-Michniewicz, Anna; Pawlowska, Elzbieta; Ochedalski, Tomasz; Piastowska-Ciesielska, Agnieszka

    2012-07-01

    Mechanical competence of bones is mainly associated with tissue quality that depends on proper bone metabolism processes. An imbalance in the regulation of bone metabolism leads to pathological changes in bone tissue leading to susceptibility to bone fractures and bone deterioration processes. Bone metabolism is regulated to a large extent by the members of the transforming growth factor-β superfamily, i.e., activins and bone morphogenetic proteins. However, their function is regulated by a single-chain protein called follistatin (FS). The aim of this study was to test the hypothesis that overexpression of FS in growing mice results in impairments in bone morphology and mechanical properties. Moreover, we wanted to investigate how geometrical, structural and material properties of bone tissue change with age. The experiment was performed on growing C57BL/6 TgNK14-mFst/6J mice, overexpressing FS (F mice) versus C57BL/6J mice used as controls (C mice). To establish how overexpression of FS influences bone tissue quality, we studied mice femurs to determine geometrical, structural and material properties of the skeleton. To determine mechanical resistance of bone tissue, femurs were loaded to failure in a three-point bending test. Obtained results indicated that overexpression of FS negatively influences bone metabolism. It was found that mutation results with a significant decrease of all measured biomechanical strength variables in F mice in comparison to C mice. Overexpression of FS leads to decreased quality of skeleton, increasing susceptibility to bone fractures.

  6. BoneCreo: a novel approach for generating a geometric model of the bone structure.

    PubMed

    Wrona, Artur

    2015-01-01

    Bones, the fundamental part of the skeleton, are constantly subjected to many biological processes including growth, feeding and remodelling. Remodelling causes changes in bone structure that may be difficult to notice on a day-to-day basis but become significant over the longer time span. It acts on the cancellous and cortical bone tissue, causing alterations in thickness and spatial arrangement in the first and alternations in pore size in the second. In healthy individuals such changes are a part of the natural bone remodelling process explained by Wolff's law. However, the direction of such changes is difficult to predict in patients in various pathological states in which bone health is affected. Here, we present a method to generate a computer based geometric model of the bone structure based on the cancellous tissue structure images. As a result we obtained a geometric model of the structure corresponding to the physical model of the cancellous bone. Such a model can be used in computer simulation to predict the remodelling changes in the healthy and pathological bone structures.

  7. Biomimetic approaches in bone tissue engineering: Integrating biological and physicomechanical strategies.

    PubMed

    Fernandez-Yague, Marc A; Abbah, Sunny Akogwu; McNamara, Laoise; Zeugolis, Dimitrios I; Pandit, Abhay; Biggs, Manus J

    2015-04-01

    The development of responsive biomaterials capable of demonstrating modulated function in response to dynamic physiological and mechanical changes in vivo remains an important challenge in bone tissue engineering. To achieve long-term repair and good clinical outcomes, biologically responsive approaches that focus on repair and reconstitution of tissue structure and function through drug release, receptor recognition, environmental responsiveness and tuned biodegradability are required. Traditional orthopedic materials lack biomimicry, and mismatches in tissue morphology, or chemical and mechanical properties ultimately accelerate device failure. Multiple stimuli have been proposed as principal contributors or mediators of cell activity and bone tissue formation, including physical (substrate topography, stiffness, shear stress and electrical forces) and biochemical factors (growth factors, genes or proteins). However, optimal solutions to bone regeneration remain elusive. This review will focus on biological and physicomechanical considerations currently being explored in bone tissue engineering.

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

    PubMed

    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.

  9. Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology

    PubMed Central

    Bodle, Josephine C.; Hanson, Ariel D.

    2011-01-01

    This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application. PMID:21338267

  10. The orthotropic elastic properties of fibrolamellar bone tissue in juvenile white-tailed deer femora.

    PubMed

    Barrera, John W; Le Cabec, Adeline; Barak, Meir M

    2016-10-01

    Fibrolamellar bone is a transient primary bone tissue found in fast-growing juvenile mammals, several species of birds and large dinosaurs. Despite the fact that this bone tissue is prevalent in many species, the vast majority of bone structural and mechanical studies are focused on human osteonal bone tissue. Previous research revealed the orthotropic structure of fibrolamellar bone, but only a handful of experiments investigated its elastic properties, mostly in the axial direction. Here we have performed for the first time an extensive biomechanical study to determine the elastic properties of fibrolamellar bone in all three orthogonal directions. We have tested 30 fibrolamellar bone cubes (2 × 2 × 2 mm) from the femora of five juvenile white-tailed deer (Odocoileus virginianus) in compression. Each bone cube was compressed iteratively, within its elastic region, in the axial, transverse and radial directions, and bone stiffness (Young's modulus) was recorded. Next, the cubes were kept for 7 days at 4 °C and then compressed again to test whether bone stiffness had significantly deteriorated. Our results demonstrated that bone tissue in the deer femora has an orthotropic elastic behavior where the highest stiffness was in the axial direction followed by the transverse and the radial directions (21.6 ± 3.3, 17.6 ± 3.0 and 14.9 ± 1.9 Gpa, respectively). Our results also revealed a slight non-significant decrease in bone stiffness after 7 days. Finally, our sample size allowed us to establish that population variance was much bigger in the axial direction than the radial direction, potentially reflecting bone adaptation to the large diversity in loading activity between individuals in the loading direction (axial) compared with the normal (radial) direction. This study confirms that the mechanically well-studied human transverse-isotropic osteonal bone is just one possible functional adaptation of bone tissue and that other vertebrate species use

  11. Mechanical stimulation of tissue repair in the hydraulic bone chamber.

    PubMed

    Guldberg, R E; Caldwell, N J; Guo, X E; Goulet, R W; Hollister, S J; Goldstein, S A

    1997-08-01

    A hydraulically activated bone chamber model was utilized to investigate cellular and microstructural mechanisms of mechanical adaptation during bone repair. Woven trabecular bone and fibrotic granulation tissue filled the initially empty chambers by 8 weeks postimplantation into canine tibial and femoral metaphyses. Without mechanical stimulation, active bone remodeling to lamellar trabecular bone and reconstitution of marrow elements were observed between 8 and 24 weeks. In subsequent loading studies, the hydraulic mechanism was activated on one randomly chosen side of 10 dogs following 8 weeks of undisturbed bone repair. The loading treatment applied an intermittent compressive force (18 N, 1.0 Hz, 1800 cycles/day) for durations of a few days up to 12 weeks. Stereological analysis of three-dimensional microcomputed tomography images revealed an increase in trabecular plate thickness and connectivity associated with the loaded repair tissue microstructure relative to unloaded contralateral controls. These microstructural alterations corresponded to an over 600% increase in the apparent modulus of the loaded bone tissue. A significant increase in the percentage of trabecular surfaces lined by osteoblasts immunopositive for type I procollagen after a few days of loading provided further evidence for mechanical stimulation of bone matrix synthesis. The local principal tissue strains associated with these adaptive changes were estimated to range from approximately -2000 to +3000 mustrain using digital image-based finite element methods. This study demonstrates the sensitivity of bone tissue and cells to a controlled in vivo mechanical stimulus and identifies microstructural mechanisms of mechanical adaptation during bone repair. The hydraulic bone chamber is introduced as an efficient experimental model to study the effects of mechanical and biological factors on bone repair and regeneration.

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

    PubMed

    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.

  13. Titanium phosphate glass microspheres for bone tissue engineering.

    PubMed

    Lakhkar, Nilay J; Park, Jeong-Hui; Mordan, Nicola J; Salih, Vehid; Wall, Ivan B; Kim, Hae-Won; King, Scott P; Hanna, John V; Martin, Richard A; Addison, Owen; Mosselmans, J Fred W; Knowles, Jonathan C

    2012-11-01

    We have demonstrated the successful production of titanium phosphate glass microspheres in the size range of ∼10-200 μm using an inexpensive, efficient, easily scalable process and assessed their use in bone tissue engineering applications. Glasses of the following compositions were prepared by melt-quench techniques: 0.5P₂O₅-0.4CaO-(0.1-x)Na₂O-xTiO₂, where x=0.03, 0.05 and 0.07 mol fraction (denoted as Ti3, Ti5 and Ti7 respectively). Several characterization studies such as differential thermal analysis, degradation (performed using a novel time lapse imaging technique) and pH and ion release measurements revealed significant densification of the glass structure with increased incorporation of TiO₂ in the glass from 3 to 5 mol.%, although further TiO₂ incorporation up to 7 mol.% did not affect the glass structure to the same extent. Cell culture studies performed using MG63 cells over a 7-day period clearly showed the ability of the microspheres to provide a stable surface for cell attachment, growth and proliferation. Taken together, the results confirm that 5 mol.% TiO₂ glass microspheres, on account of their relative ease of preparation and favourable biocompatibility, are worthy candidates for use as substrate materials in bone tissue engineering applications.

  14. Finite Element Method (FEM), Mechanobiology and Biomimetic Scaffolds in Bone Tissue Engineering

    PubMed Central

    Boccaccio, A.; Ballini, A.; Pappalettere, C.; Tullo, D.; Cantore, S.; Desiate, A.

    2011-01-01

    tissue engineering is given. Firstly, the generalities of the finite element method of structural analysis are outlined; second, the issues related to the generation of a finite element model of a given anatomical site or of a bone scaffold are discussed; thirdly, the principles on which mechanobiology is based, the principal theories as well as the main applications of mechano-regulation models in bone tissue engineering are described; finally, the limitations of the mechanobiological models and the future perspectives are indicated. PMID:21278921

  15. Finite element method (FEM), mechanobiology and biomimetic scaffolds in bone tissue engineering.

    PubMed

    Boccaccio, A; Ballini, A; Pappalettere, C; Tullo, D; Cantore, S; Desiate, A

    2011-01-26

    engineering is given. Firstly, the generalities of the finite element method of structural analysis are outlined; second, the issues related to the generation of a finite element model of a given anatomical site or of a bone scaffold are discussed; thirdly, the principles on which mechanobiology is based, the principal theories as well as the main applications of mechano-regulation models in bone tissue engineering are described; finally, the limitations of the mechanobiological models and the future perspectives are indicated.

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

    PubMed

    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

  17. Musculoskeletal lymphoma: MRI of bone or soft tissue presentations.

    PubMed

    Carroll, Gemma; Breidahl, William; Robbins, Peter

    2013-12-01

    To assess the MRI findings of musculoskeletal lymphoma primarily presenting clinically as a bone lesion or soft tissue mass. Magnetic resonance imaging of 23 cases of musculoskeletal lymphoma were retrospectively reviewed. Features assessed included tumour location, morphology, signal intensity (SI) characteristics, cortical destruction, involvement of multiple anatomic compartments, encasement of adjacent neurovascular structures/tendons and subcutaneous oedema. Osseous lesions were typically poorly defined and hypointense on T1-weighted imaging. T2-weighted SI was usually heterogeneous, with 54% of cases having a 'mosaic' pattern of marrow replacement. Ninety-two per cent of osseous tumours had cortical abnormalities, most commonly a permeative pattern. A periosseous soft tissue cuff was present in 46% of cases while 38% had a more significant extraosseous component. All cases of soft tissue lymphoma were iso-/slightly hyperintense to muscle on T1-weighted images and hyperintense on T2-weighted images. Multicompartment involvement by extraosseous tumour was present in 75% of cases, and 67% had subcutaneous oedema. Eighty-three per cent of soft tissue tumours showed encasement of adjacent structures. Multifocal lymphoma had similar morphology and SI characteristics to single-site lesions. Histopathologically, there were 21 cases of non-Hodgkin's lymphoma and two of Hodgkin's lymphoma. Magnetic resonance imaging features of primary osseous lymphoma include T2 heterogeneity, a periosseous soft tissue cuff or a more substantial mass, and cortical disruption often disproportionate to the extent of extraosseous tumour. Features characteristic of soft tissue lymphoma include relative homogeneity on T1- and T2-weighted imaging, multicompartment involvement and encasement of neurovascular structures. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

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

    PubMed

    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.

  19. Tissue engineering construct on the basis of multipotent stromal adipose tissue cells and Osteomatrix for regeneration of the bone tissue.

    PubMed

    Bukharova, T B; Arutyunyan, I V; Shustrov, S A; Alekseeva, I S; Fedyunina, I A; Logovskaya, L V; Volkov, A V; Rzhaninova, A A; Grigor'yan, A S; Kulakov, A A; Gol'dshtein, D V

    2011-11-01

    We developed a new method of creation of tissue engineering constructs for regeneration of the bone tissue based on the principle of free distribution of cells in a fibrin clot within a scaffold. The tissue engineering construct includes multipotent stromal adipose tissue cells committed in osteogenic lineage, platelet-rich plasma, and resorbed material on the basis of xenogeneic bone collagen. The culture of bone progenitor cells was characterized by the main markers of osteoblastic differon. The material meets all requirements for materials intended for tissue engineering. An innovative high-technological tissue engineering product for clinical application is prepared.

  20. Determinants of Long Bone Structural Properties

    NASA Technical Reports Server (NTRS)

    Cleek, T. M.; Katz, B.; Whalen, R. T.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    The objective of our research is to determine whether a non-invasive determination of long bone cross-sectional areal properties using only the mineral component of bone accurately predicts the true structural properties. In this study section properties of a whole long bone were compared using two methods: (1) special analysis of bone densitometry data, and (2) experimental determination of flexural rigidities from bone surface strain measurements during controlled loading.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    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.

  5. Carbon nanotubes with high bone-tissue compatibility and bone-formation acceleration effects.

    PubMed

    Usui, Yuki; Aoki, Kaoru; Narita, Nobuyo; Murakami, Narumichi; Nakamura, Isao; Nakamura, Koichi; Ishigaki, Norio; Yamazaki, Hiroshi; Horiuchi, Hiroshi; Kato, Hiroyuki; Taruta, Seiichi; Kim, Yoong Ahm; Endo, Morinobu; Saito, Naoto

    2008-02-01

    Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.

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

    PubMed Central

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

    2013-01-01

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

  7. Automated Localization of Multiple Pelvic Bone Structures on MRI.

    PubMed

    Onal, Sinan; Lai-Yuen, Susana; Bao, Paul; Weitzenfeld, Alfredo; Hart, Stuart

    2016-01-01

    In this paper, we present a fully automated localization method for multiple pelvic bone structures on magnetic resonance images (MRI). Pelvic bone structures are at present identified manually on MRI to locate reference points for measurement and evaluation of pelvic organ prolapse (POP). Given that this is a time-consuming and subjective procedure, there is a need to localize pelvic bone structures automatically. However, bone structures are not easily differentiable from soft tissue on MRI as their pixel intensities tend to be very similar. In this paper, we present a model that combines support vector machines and nonlinear regression capturing global and local information to automatically identify the bounding boxes of bone structures on MRI. The model identifies the location of the pelvic bone structures by establishing the association between their relative locations and using local information such as texture features. Results show that the proposed method is able to locate the bone structures of interest accurately (dice similarity index >0.75) in 87-91% of the images. This research aims to enable accurate, consistent, and fully automated localization of bone structures on MRI to facilitate and improve the diagnosis of health conditions such as female POP.

  8. Importance of dual delivery systems for bone tissue engineering.

    PubMed

    Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

    2016-03-10

    Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Automating the Processing Steps for Obtaining Bone Tissue-Engineered Substitutes: From Imaging Tools to Bioreactors

    PubMed Central

    Costa, Pedro F.; Martins, Albino; Neves, Nuno M.; Gomes, Manuela E.

    2014-01-01

    Bone diseases and injuries are highly incapacitating and result in a high demand for tissue substitutes with specific biomechanical and structural features. Tissue engineering has already proven to be effective in regenerating bone tissue, but has not yet been able to become an economically viable solution due to the complexity of the tissue, which is very difficult to be replicated, eventually requiring the utilization of highly labor-intensive processes. Process automation is seen as the solution for mass production of cellularized bone tissue substitutes at an affordable cost by being able to reduce human intervention as well as reducing product variability. The combination of tools such as medical imaging, computer-aided fabrication, and bioreactor technologies, which are currently used in tissue engineering, shows the potential to generate automated production ecosystems, which will, in turn, enable the generation of commercially available products with widespread clinical application. PMID:24673688

  10. Engineered bone tissue associated with vascularization utilizing a rotating wall vessel bioreactor.

    PubMed

    Nishi, Masanori; Matsumoto, Rena; Dong, Jian; Uemura, Toshimasa

    2013-02-01

    Tissue-engineered bone has attracted much attention as an alternative material for bone grafting; however, implantable bone tissue of an appropriate size and shape for clinical use has not yet been developed due to a lack of vascularization, which results in necrosis of the seeded cells in vivo. This is the first report of bone tissue engineering associated with vascularization by co-culturing bone marrow mesenchymal stem cells (MSCs) with MSC-derived endothelial cells (ECs) within a porous scaffold using a rotating wall vessel (RWV) bioreactor. MSC-derived ECs were identified by immunofluorescence staining for von Willebrand factor (vWF) and by flow cytometry for CD31 expression. The tissue obtained was histochemically analyzed using toluidin blue, hematoxylin and eosin, anti-osteopontin antibody, anti-osteocalcin antibody, and tomato-lectin stain. Results showed that bone tissue containing vascular-like structures was generated. Three-dimensional culture condition created by medium flow in the RWV vessel and the interaction of MSCs with MSC-derived ECs might provide the cells an advantage in the construction of three-dimensional bone tissue with blood vessels.

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

    PubMed

    Chinsamy, Anusuya; Tumarkin-Deratzian, Allison

    2009-09-01

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

  12. Effects of magnesium intake deficiency on bone metabolism and bone tissue around osseointegrated implants.

    PubMed

    Belluci, Marina Montosa; Giro, Gabriela; del Barrio, Ricardo Andrés Landazuri; Pereira, Rosa Maria Rodrigues; Marcantonio, Elcio; Orrico, Silvana Regina Perez

    2011-07-01

    This study evaluated the effect of magnesium dietary deficiency on bone metabolism and bone tissue around implants with established osseointegration. For this, 30 rats received an implant in the right tibial metaphysis. After 60 days for healing of the implants, the animals were divided into groups according to the diet received. Control group (CTL) received a standard diet with adequate magnesium content, while test group (Mg) received the same diet except for a 90% reduction of magnesium. The animals were sacrificed after 90 days for evaluation of calcium, magnesium, osteocalcin and parathyroid hormone (PTH) serum levels and the deoxypyridinoline (DPD) level in the urine. The effect of magnesium deficiency on skeletal bone tissue was evaluated by densitometry of the lumbar vertebrae, while the effect of bone tissue around titanium implants was evaluated by radiographic measurement of cortical bone thickness and bone density. The effect on biomechanical characteristics was verified by implant removal torque testing. Magnesium dietary deficiency resulted in a decrease of the magnesium serum level and an increase of PTH and DPD levels (P ≤ 0.05). The Mg group also presented a loss of systemic bone mass, decreased cortical bone thickness and lower values of removal torque of the implants (P ≤ 0.01). The present study concluded that magnesium-deficient diet had a negative influence on bone metabolism as well as on the bone tissue around the implants. © 2010 John Wiley & Sons A/S.

  13. Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials.

    PubMed

    Reddi, A H

    2000-08-01

    Morphogenesis is the developmental cascade of pattern formation, body plan establishment, and the architecture of mirror-image bilateral symmetry of many structures and asymmetry of some, culminating in the adult form. Tissue engineering is the emerging discipline of design and construction of spare parts for the human body to restore function based on principles of molecular developmental biology and morphogenesis governed by bioengineering. The three key ingredients for both morphogenesis and tissue engineering are inductive signals, responding stem cells, and the extracellular matrix. Among the many tissues in the human body, bone has considerable powers for regeneration and is a prototype model for tissue engineering based on morphogenesis. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and permitted the isolation of bone morphogens. Although it is traditional to study morphogenetic signals in embryos, bone morphogenetic proteins (BMPs), the inductive signals for bone, were isolated from demineralized bone matrix from adults. BMPs and related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote, and maintain chondrogenesis and osteogenesis and have actions beyond bone. The symbiosis of bone inductive and conductive strategies are critical for tissue engineering, and is in turn governed by the context and biomechanics. The context is the microenvironment, consisting of extracellular matrix, which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion proteins including fibronectins. Thus, the rules of architecture for tissue engineering are an imitation of the laws of developmental biology and morphogenesis, and thus may be universal for all tissues, including bones and joints.

  14. Bone Tissue Scaffold Technologies Based on RP Adopted Droplet Assembly

    DTIC Science & Technology

    2003-04-01

    poly (L- lactic acid ) scaffolds for bone tissue engineering via extrusion, Scripta Materialia, 2001, 45: 773-779. 12. Zhuo Xiong, Yongnian Yan, Shengguo... lactic acid ) and tri-calcium phosphate (TCP) was chosen to form bone tissue engineering scaffolds. The new computer aided manufacturing process can make...processing to form a variety of shapes and sizes. Biodegradable biomaterials, poly (L- lactic acid ) (PLLA), tricalcium phosphate (TCP) and their composites

  15. Management of soft tissue and bone sarcomas

    SciTech Connect

    Van Oosterom, A.T.; Van Unnik, J.A.M.

    1986-01-01

    This book contains 32 papers. Some of the titles are: Adjuvant Treatment for Osteosarcoma of the Limbs; Trial 20781 of the SIOP and the EORTC Radiotherapy/Chemotherapy; Application of Magnetic Resonance Imaging (MRI) in Diagnosis and Follow-up During Treatment of Bone Tumors; Radiological Assessment of Local Involvement in Bone Sarcomas; and Prevention of Lung Metastases by Irradiation Alone or Combined with Chemotherapy in an Animal Model.

  16. Silk scaffolds in bone tissue engineering: An overview.

    PubMed

    Bhattacharjee, Promita; Kundu, Banani; Naskar, Deboki; Kim, Hae-Won; Maiti, Tapas K; Bhattacharya, Debasis; Kundu, Subhas C

    2017-09-20

    Bone tissue plays multiple roles in our day-to-day functionality. The frequency of accidental bone damage and disorder is increasing worldwide. Moreover, as the world population continues to grow, the percentage of the elderly population continues to grow, which results in an increased number of bone degenerative diseases. This increased elderly population pushes the need for artificial bone implants that specifically employ biocompatible materials. A vast body of literature is available on the use of silk in bone tissue engineering. The current work presents an overview of this literature from materials and fabrication perspective. As silk is an easy-to-process biopolymer; this allows silk-based biomaterials to be molded into diverse forms and architectures, which further affects the degradability. This makes silk-based scaffolds suitable for treating a variety of bone reconstruction and regeneration objectives. Silk surfaces offer active sites that aid the mineralization and/or bonding of bioactive molecules that facilitate bone regeneration. Silk has also been blended with a variety of polymers and minerals to enhance its advantageous properties or introduce new ones. Several successful works, both in vitro and in vivo, have been reported using silk-based scaffolds to regenerate bone tissues or other parts of the skeletal system such as cartilage and ligament. A growing trend is observed toward the use of mineralized and nanofibrous scaffolds along with the development of technology that allows to control scaffold architecture, its biodegradability and the sustained releasing property of scaffolds. Further development of silk-based scaffolds for bone tissue engineering, taking them up to and beyond the stage of human trials, is hoped to be achieved in the near future through a cross-disciplinary coalition of tissue engineers, material scientists and manufacturing engineers. The state-of-art of silk biomaterials in bone tissue engineering, covering their wide

  17. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    PubMed Central

    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. PMID:28194185

  18. Distinctive Head and Neck Bone and Soft Tissue Neoplasms.

    PubMed

    Purgina, Bibianna; Lai, Chi K

    2017-03-01

    Benign and malignant primary bone and soft tissue lesions of the head and neck are rare. The uncommon nature of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, radiographic, and pathologic features of selected bone and soft tissue tumors involving the head and neck region, including angiofibroma, glomangiopericytoma, rhabdomyosarcoma, biphenotypic sinonasal sarcoma, chordoma, chondrosarcoma, and osteosarcoma. Emphasis is placed on key diagnostic pitfalls, differential diagnosis, and the importance of correlating clinical and radiographic information, particularly for tumors involving bone.

  19. Effect of Microgravity on Bone Tissue and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Session TA4 includes short reports concerning: (1) Human Bone Tissue Changes after Long-Term Space Flight: Phenomenology and Possible Mechanics; (2) Prediction of Femoral Neck Bone Mineral Density Change in Space; (3) Dietary Calcium in Space; (4) Calcium Metabolism During Extended-Duration Space Flight; (5) External Impact Loads on the Lower Extremity During Jumping in Simulated Microgravity and the Relationship to Internal Bone Strain; and (6) Bone Loss During Long Term Space Flight is Prevented by the Application of a Short Term Impulsive Mechanical Stimulus.

  20. NOTE: New tissue substitutes representing cortical bone and adipose tissue in quantitative radiology

    NASA Astrophysics Data System (ADS)

    Sanada, Shigeru; Kawahara, Kazuhiro; Yamamoto, Tomoyuki; Takashima, Tsutomu

    1999-06-01

    To employ quantitative radiology more accurately, we examined phantom materials for cortical bone and adipose tissue as calibration standards and as experimental phantoms. New tissue substitutes for cortical bone and adipose tissue composed of liquid phantom were verified by computing their attenuation coefficients and observing their chemical properties. We showed that a potassium pyrophosphate (K4P2O7) solution for cortical bone was comparable to a dipotassium hydrogen phosphate (K2HPO4) solution. Also, the use of methyl alcohol for adipose tissue was more suitable than ethyl alcohol as a phantom material because of its physical and chemical properties.

  1. Cell Sources for Bone Tissue Engineering: Insights from Basic Science

    PubMed Central

    2011-01-01

    One of the goals of bone tissue engineering is to design delivery methods for skeletal stem/progenitor cells to repair or replace bone. Although the materials used to retain cells play a central role in the quality of the constructs, the source of cells is key for bone regeneration. Bone marrow is the most common cell source, but other tissues are now being explored, such as the periosteum, fat, muscle, cord blood, and embryonic or induced pluripotent stem cells. The therapeutic effect of exogenous stem/progenitor cells is accepted, yet their contribution to bone repair is not well defined. The in vitro osteo- and/or chondrogenic potential of these skeletal progenitors do not necessarily predict their differentiation potential in vivo and their function may be affected by their ability to home correctly to bone. This review provides an overview of animal models used to test the efficacy of cell-based approaches. We examine the mechanisms of endogenous cell recruitment during bone repair and compare the role of local versus systemic cell recruitment. We discuss how the normal repair process can help define efficacious cell sources for bone tissue engineering and improve their methods of delivery. PMID:21902612

  2. Ultrasound elastography assessment of bone/soft tissue interface

    NASA Astrophysics Data System (ADS)

    Parmar, Biren J.; Yang, Xu; Chaudhry, Anuj; Shafeeq Shajudeen, Peer; Nair, Sanjay P.; Weiner, Bradley K.; Tasciotti, Ennio; Krouskop, Thomas A.; Righetti, Raffaella

    2016-01-01

    We report on the use of elastographic imaging techniques to assess the bone/soft tissue interface, a region that has not been previously investigated but may provide important information about fracture and bone healing. The performance of axial strain elastograms and axial shear strain elastograms at the bone/soft tissue interface was studied ex vivo on intact and fractured canine and ovine tibias. Selected ex vivo results were corroborated on intact sheep tibias in vivo. The elastography results were statistically analyzed using elastographic image quality tools. The results of this study demonstrate distinct patterns in the distribution of the normalized local axial strains and axial shear strains at the bone/soft tissue interface with respect to the background soft tissue. They also show that the relative strength and distribution of the elastographic parameters change in the presence of a fracture and depend on the degree of misalignment between the fracture fragments. Thus, elastographic imaging modalities might be used in the future to obtain information regarding the integrity of bones and to assess the severity of fractures, alignment of bone fragments as well as to follow bone healing.

  3. 3D-Printing Composite Polycaprolactone-Decellularized Bone Matrix Scaffolds for Bone Tissue Engineering Applications.

    PubMed

    Rindone, Alexandra N; Nyberg, Ethan; Grayson, Warren L

    2017-05-11

    Millions of patients worldwide require bone grafts for treatment of large, critically sized bone defects from conditions such as trauma, cancer, and congenital defects. Tissue engineered (TE) bone grafts have the potential to provide a more effective treatment than current bone grafts since they would restore fully functional bone tissue in large defects. Most bone TE approaches involve a combination of stem cells with porous, biodegradable scaffolds that provide mechanical support and degrade gradually as bone tissue is regenerated by stem cells. 3D-printing is a key technique in bone TE that can be used to fabricate functionalized scaffolds with patient-specific geometry. Using 3D-printing, composite polycaprolactone (PCL) and decellularized bone matrix (DCB) scaffolds can be produced to have the desired mechanical properties, geometry, and osteoinductivity needed for a TE bone graft. This book chapter will describe the protocols for fabricating and characterizing 3D-printed PCL:DCB scaffolds. Moreover, procedures for culturing adipose-derived stem cells (ASCs) in these scaffolds in vitro will be described to demonstrate the osteoinductivity of the scaffolds.

  4. Treatment of bone and soft tissue defects in infected nonunion.

    PubMed

    Fleischmann, W; Suger, G; Kinzl, L

    1992-01-01

    In the treatment of infected pseudarthroses the general principles of osteitis treatment are applied. This includes radical excision of pseudarthrotic and infected bone tissue, and of diseased surrounding soft tissue. External fixation devices are the preferred method of stabilization of the bone. Based on the data of a retrospective study of 31 Papineau procedures, 65 local flap transfers, and 46 free flap transfers we found that the Papineau procedure works in minor bone and soft tissue defects. Unstable scar formation is a major disadvantage of this method. Local muscular flaps are indicated in the treatment of soft tissue defects in the proximal and medial portions of the lower leg. A prerequisite for free flap transfers is the availability of trained personnel and suitable technical equipment. The option is limited by the patient's vascular situation. This kind of tissue transfer seems to be superior to other methods. For the substitution of bone defects corticocancellous bone transplantation may be used. A promising alternative method to deal with extensive bone defects is osteogenesis produced by callus distraction.

  5. Nanoceramics on osteoblast proliferation and differentiation in bone tissue engineering.

    PubMed

    S, Sai Nievethitha; N, Subhapradha; D, Saravanan; N, Selvamurugan; Tsai, Wei-Bor; N, Srinivasan; R, Murugesan; A, Moorthi

    2017-05-01

    Bone, a highly dynamic connective tissue, consist of a bioorganic phase comprising osteogenic cells and proteins which lies over an inorganic phase predominantly made of CaPO4 (biological apatite). Injury to bone can be due to mechanical, metabolic or inflammatory agents also owing pathological conditions like fractures, osteomyelitis, osteolysis or cysts may arise in enameloid, chondroid, cementum, or chondroid bone which forms the intermediate tissues of the body. Bone tissue engineering (BTE) applies bioactive scaffolds, host cells and osteogenic signals for restoring damaged or diseased tissues. Various bioceramics used in BTE can be bioactive (like glass ceramics and hydroxyapatite bioactive glass), bioresorbable (like tricalcium phosphates) or bioinert (like zirconia and alumina). Limiting the size of these materials to nano-scale has resulted in a higher surface area to volume ratio thereby improving multi-functionality, solubility, surface catalytic activity, high heat and electrical conductivity. Nanoceramics have been found to induce osteoconduction, osteointegration, osteogenesis and osteoinduction. The present review aims at summarizing the interactions of nanoceramics and osteoblast/stem cells for promoting the proliferation and differentiation of the osteoblast cells by nanoceramics as superior bone substitutes in bone tissue engineering applications.

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

    NASA Technical Reports Server (NTRS)

    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.

  7. Measures of Complexity to quantify Bone Structure

    NASA Astrophysics Data System (ADS)

    Saparin, Peter; Gowin, Wolfgang; Kurths, Jürgen; Felsenberg, Dieter

    1998-03-01

    We propose a technique to assess structure of the bone in its spatial distribution by describing and quantifying the structural architecture as a whole. The concept of measures of complexity based on symbolic dynamics is applied to computed tomography (CT) - images obtained from human lumbar vertebra. CT-images have been transformed into images consisting of 5 different symbols, whereby both statical and dynamical coding are included. Different aspects of the bone structure are quantified by several measures which have been introduced: index of global ensemble of elements composing the bone; complexity, homogeneity and dynamics within the bone architecture; complexity and inhomogeneity of the trabecular net. This leads to new insides to the understanding of bone's internal structure. The results give the first experimental and quantitative evidence of the theoretical prediction that complexity of bone structure declines rapidly with the increased disintegration of bone structures leading to the loss of bone mass and specify experimentally that bone structure is exponentially related to its density. Especially, osteoporotic vertebrae are less complex organized than normal ones. In addition, this method is significantly sensitive to changes in bone structure and provides improvements of diagnostic of pathological structural loss.

  8. Tissue Engineering Strategies for Promoting Vascularized Bone Regeneration

    PubMed Central

    Almubarak, Sarah; Nethercott, Hubert; Freeberg, Marie; Beaudon, Caroline; Jha, Amit; Jackson, Wesley; Marcucio, Ralph; Miclau, Theodore; Healy, Kevin; Bahney, Chelsea

    2016-01-01

    This review focuses on current tissue engineering strategies for promoting vascularized bone regeneration. We review the role of angiogenic growth factors in promoting vascularized bone regeneration and discuss the different therapeutic strategies for controlled/sustained growth factor delivery. Next, we address the therapeutic uses of stem cells in vascularized bone regeneration. Specifically, this review addresses the concept of co-culture using osteogenic and vasculogenic stem cells, and how adipose derived stem cells compare to bone marrow derived mesenchymal stem cells in the promotion of angiogenesis. We conclude this review with a discussion of a novel approach to bone regeneration through a cartilage intermediate, and discuss why it has the potential to be more effective than traditional bone grafting methods. PMID:26608518

  9. [Impedance testing of compact bone tissue in hypokinetic rats].

    PubMed

    Berezovs'kyĭ, V Ia; Levashov, O M; Safonov, S L; Levashov, M I; Litovka, I H

    2005-01-01

    The bioelectrical impedance method was used for determination of compact bone status in white rats after 28th days of strong hypokinesia. It was shown that the lowering of mechanical loading leads to disturbances in dielectric properties and changes in electrical impedance parameters. These disturbances had different direction and manifestation. It was distinguished the two typical variants of bone dielectric properties changes. The first variant was more characteristic for early stages of hypokinetic osteodestruction, the second variant was more characteristic for the fully development hypokinetic disturbances. It was determine a correlation between the changes in electrical impedance parameters and mane components of bone matrix. The results of this study show that hyperhydratation of bone tissue play important role in hypokinetic changes of bone dielectric properties. Electroimpedance method may be used for early diagnostic of bone state in clinic and experiments.

  10. Novel hybrid materials for preparation of bone tissue engineering scaffolds.

    PubMed

    Lewandowska-Łańcucka, Joanna; Fiejdasz, Sylwia; Rodzik, Łucja; Łatkiewicz, Anna; Nowakowska, Maria

    2015-09-01

    The organic-inorganic hybrid systems based on biopolymer hydrogels with dispersed silica nanoparticles were obtained and characterized in terms of their physicochemical properties, cytocompatibility and bioactivity. The hybrid materials were prepared in a form of collagen and collagen-chitosan sols to which the silica nanoparticles of two different sizes were incorporated. The ability of these materials to undergo in situ gelation under physiological temperature was assessed by microviscosity and gelation time determination based on steady-state fluorescence anisotropy measurements. The effect of silica nanoparticles addition on the physicochemical properties (surface wettability, swellability) of hybrid materials was analyzed and compared with those characteristic for pristine collagen and collagen-chitosan hydrogels. Biological studies indicate that surface wettability determined in terms of contact angle for all of the hybrids prepared is optimal and thus can provide satisfactory adhesion of fibroblasts. Cytotoxicity test results showed high metabolic activity of mouse as well as human fibroblast cell lines cultured on hybrid materials. The composition of hybrids was optimized in terms of concentration of silica nanoparticles. The effect of silica on the formation of bone-like mineral structures on exposition to simulated body fluid was determined. SEM images revealed mineral phase formation not only at the surfaces but also in the whole volumes of all hybrid materials developed suggesting their usefulness for bone tissue engineering. EDS and FTIR analyses indicated that these mineral phases consist of apatite-like structures.

  11. Physiological bases of bone regeneration I. Histology and physiology of bone tissue.

    PubMed

    Fernández-Tresguerres-Hernández-Gil, Isabel; Alobera-Gracia, Miguel Angel; del-Canto-Pingarrón, Mariano; Blanco-Jerez, Luis

    2006-01-01

    Bone is the only body tissue capable of regeneration, allowing the restitutio ad integrum following trauma. In the event of a fracture or bone graft, new bone is formed, which following the remodeling process is identical to the pre-existing. Bone is a dynamic tissue in constant formation and resorption. This balanced phenomena, known as the remodeling process, allows the renovation of 5-15% of the total bone mass per year under normal conditions. Bone remodeling consists of the resorption of a certain amount of bone by osteoclasts, likewise the formation of osteoid matrix by osteoblasts, and its subsequent mineralization. This phenomenon occurs in small areas of the cortical bone or the trabecular surface, called Basic Multicellular Units (BMU). Treatment in Traumatology, Orthopedics, Implantology, and Maxillofacial and Oral Surgery, is based on the biologic principals of bone regeneration, in which cells, extracellular matrix, and osteoinductive signals are involved. The aim of this paper is to provide an up date on current knowledge on the biochemical and physiological mechanisms of bone regeneration, paying particular attention to the role played by the cells and proteins of the bone matrix.

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

    NASA Astrophysics Data System (ADS)

    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

  13. Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

    PubMed Central

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

    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 osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering 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. PMID:26273505

  14. Comparative histomorphometric study of bone tissue synthesized after electric and ultrasound stimulation.

    PubMed

    Coman, Mălina; Hîncu, Mihaela; Surlin, Petra; Mateescu, Garofiţa; Nechita, A; Banu, Mihaela

    2011-01-01

    The clinical use of the alternative therapies in traumatology is conditioned by the knowledge and understanding of their actions on the bone tissue. The hereby study aims at the comparative assessment of the effectiveness of the direct current and ultrasounds in treating the fractures. Thus, we have proceeded to a comparative histological study of the bone tissue in the fractured area and the biomechanical description and the three-dimensional model of the stimulated bone's behavior by using micro-CT X-rays and the finite element analysis. The findings clearly show that the bone, which has been stimulated during a period of two weeks, has regained its functions, that is 85% of the compression one and 95% of the shearing one. These values prove that 90% of the bone structure has healed.

  15. Age related changes in the bone tissue under conditions of hypokinesia

    NASA Technical Reports Server (NTRS)

    Podrushnyak, E. P.; Suslov, E. I.

    1980-01-01

    Microroentgenography of nine young people, aged 24-29, before and after hypokinesia (16-37 days strict bed rest), showed that the heel bone density of those with initially high bone density generally decreased and that of those with initially low bone density generally increased. X-ray structural analysis of the femurs of 25 corpses of accidentally killed healthy people, aged 18-70, data are presented and discussed, with the conclusion that the bone hydroxyapatite crystal structure stabilizes by ages 20 to 25, is stable from ages 25 to 60 and decreases in density after age 60. It is concluded that bone tissue structure changes, both with age, and in a comparatively short time in hypokinesia.

  16. Internal channel structures in trabecular bone

    NASA Astrophysics Data System (ADS)

    Scherf, Heike; Beckmann, Felix; Fischer, Jens; Witte, Frank

    2004-10-01

    Material properties of bone are crucial for studies regarding the mechanical behavior of bone. The mechanical behavior depends on the macro- and micro-architecture as well as the organic and mineral content of bone. The marco-architecture of bone is normally analyzed by plane radiographs. The micro-architecture of the trabecular bone can be imaged by high resolution CT imaging techniques using conventional x-ray tubes. However, fine structures in bone architecture cannot be sufficiently analyzed by this technique due to its limited resolution. High resolution CT imaging technique using synchrotron radiation generates images with a high spatial resolution of bone structures on a micron scale. Additionally, this imaging technique provides superior determination of local differences in the bone mineral density. Two microtomography techniques, first: based on conventional x-ray tubes and second: based on synchrotron radiation were compared in this study to detect fine bone structures such as inner trabecular channels. In two red howler monkeys (Alouatta seniculus) femora channel structures were found inside the trabecular bone by both techniques. Only synchrotron-based microtomography was able to detect layers of lower mineral density in the channel walls. The found structures in trabecular bone are normally expected in the Haversian channel walls of the cortical bone. However, the origin of the trabecular channel structure is not fully understood. We found, that synchrotron-based microtomography is a very valuable technique in the research of fine bone structures. Further research should focus on the impact of these findings on the mechanical properties of trabecular bone.

  17. Tissue integration of the collagen-hydroxylapatite implant: histological examination in canine bone and surrounding tissues.

    PubMed

    Remacle, M; Marbaix, E; Mustin, V

    1991-01-01

    Using the dog as an animal model, we have tested an implant material composed of purified fibrillar collagen (PFC) and particulate hydroxylapatite (HA) in the mandible and in surrounding tissues. Bone and tissue samples were taken at 2, 4 and 6 months for histological study. After 2 months, the PFC was replaced by fibro-connective host tissues. After 4 months, some small areas of ossification were observed around the HA particles. After 6 months, the fibro-connective tissue was replaced by neo-formed bone in the mandible. PFC was found to increase the interfaces between the HA particles and the host tissues, permitting HA integration into the bone. The PFC/HA implant was also molded when moistened by blood or saline solution and then became mis-sharpen by local pressures exerted. These findings show that the implant should preferably be reserved for the restoration of bones not subjected to significant forces or local stresses.

  18. Mechanical response tissue analyzer for estimating bone strength

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Steele, Charles; Mauriello, Anthony

    1991-01-01

    One of the major concerns for extended space flight is weakness of the long bones of the legs, composed primarily of cortical bone, that functions to provide mechanical support. The strength of cortical bone is due to its complex structure, described simplistically as cylinders of parallel osteons composed of layers of mineralized collagen. The reduced mechanical stresses during space flight or immobilization of bone on Earth reduces the mineral content, and changes the components of its matrix and structure so that its strength is reduced. Currently, the established clinical measures of bone strength are indirect. The measures are based on determinations of mineral density by means of radiography, photon absorptiometry, and quantitative computer tomography. While the mineral content of bone is essential to its strength, there is growing awareness of the limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially osteoporosis. Other experimental methods in clinical trials that more directly evaluate the physical properties of bone, and do not require exposure to radiation, include ultrasound, acoustic emission, and low-frequency mechanical vibration. The last method can be considered a direct measure of the functional capacity of a long bone since it quantifies the mechanical response to a stimulus delivered directly to the bone. A low frequency vibration induces a response (impedance) curve with a minimum at the resonant frequency, that a few investigators use for the evaluation of the bone. An alternative approach, the method under consideration, is to use the response curve as the basis for determination of the bone bending stiffness EI (E is the intrinsic material property and I is the cross-sectional moment of inertia) and mass, fundamental mechanical properties of bone.

  19. Bone structure investigation using X-ray and neutron radiography techniques.

    PubMed

    Moghaddam, K Kamali; Taheri, T; Ayubian, M

    2008-01-01

    In this paper we report a study of the periodic variation of bone tissue humidity immediately after death using both neutron and X-ray radiography techniques. After death, bone tissue experiences sequential change over time. This change consists of organic and inorganic phase variations of the bone structure, as well as gradual reduction of the bone's water content. These variations are investigated by periodically imaging dead bone using X-ray and neutron radiography. Chemical separation techniques such as calcification and decalcification were used to separate the organic and inorganic phases of the bone. Comparison between X-ray and neutron radiographs of bone following phase separation can be potentially used to investigate the bone disease or to determine a cause of death. In our experiments, we use adult rat femur bones, and the interpretations of these results are presented based on our understanding of bone structure and images produced by neutron and X-ray photon interactions.

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

    PubMed

    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.

  1. Microporous Nanofibrous Fibrin-based Scaffolds for Bone Tissue Engineering

    PubMed Central

    Osathanon, Thanaphum; Linnes, Michael L.; Rajachar, Rupak M.; Ratner, Buddy D.; Somerman, Martha J.; Giachelli, Cecilia M.

    2008-01-01

    The fibrotic response of the body to synthetic polymers limits their success in tissue engineering and other applications. Though porous polymers have demonstrated improved healing, difficulty in controlling their pore sizes and pore interconnections has clouded the understanding of this phenomenon. In this study, a novel method to fabricate natural polymer/calcium phosphate composite scaffolds with tightly controllable pore size, pore interconnection, and calcium phosphate deposition was developed. Microporous, nanofibrous fibrin scaffolds were fabricated using sphere-templating methods. Composite scaffolds were created by solution deposition of calcium phosphate on fibrin surfaces or by direct incorporation of nanocrystalline hydroxyapatite (nHA). The SEM results showed that fibrin scaffolds exhibited a highly porous and interconnected structure. Osteoblast-like cells, obtained from murine calvaria, attached, spread and showed a polygonal morphology on the surface of the biomaterial. Multiple cell layers and fibrillar matrix deposition were observed. Moreover, cells seeded on mineralized fibrin scaffolds exhibited significantly higher alkaline phosphatase activity as well as osteoblast marker gene expression compared to fibrin scaffolds and nHA incorporated fibrin scaffolds (0.25 g and 0.5 g). All types of scaffolds were degraded both in vitro and in vivo. Furthermore, these scaffolds promoted bone formation in a mouse calvarial defect model and the bone formation was enhanced by addition of rhBMP-2. PMID:18640716

  2. Tissue Engineering for Bone Production- Stem Cells, Gene Therapy and Scaffolds

    PubMed Central

    Khaled, E.G; Saleh, M; Hindocha, S; Griffin, M; Khan, Wasim S

    2011-01-01

    A bone graft has been the gold standard treatment for repairing bone defects. However, due to bone grafts associated donor site morbidity several alternative bone substitutes options have been made available but with their added expense and limited osteoinductive properties they are not ideal. Therefore, research has begun in tissue engineering to investigate stem cells, which are one of the body’s own mechanisms used to repair bone. Stem cells are clonogenic undifferentiated cells capable of self-renewal. Readily available from numerous of sources stem cells have the potential to differentiate in osteoblasts and chrondrocytes showing capability to repair both bone and cartilage. The known immunologic properties of stem cells further enhance their therapeutic appeal. Stem cells have shown to be excellent carriers for gene transfer having the capability to be transduced. Gene transfer could enable growth factors and bone morphogentic proteins to enhance bone repair. Stem cells are implanted onto scaffolds, which are structures capable of supporting tissue formation by allowing cell migration, proliferation and differentiation. Research aims to produce scaffolds that deliver and retain cells, allow for cell attachment has adequate biodegradability, biocompatibility and non-immunogenicity. However, having tried and testing numerous materials including synthetic and natural products research into the perfect scaffold product continues. This review aims to explain how stem cells were discovered, the techniques used to isolate stem cells, identify and manipulate them down different cell lineages and discuss the research into using stem cells to reconstruct bone using genetic modification and scaffolds. PMID:21886695

  3. Repeated freeze-thawing of bone tissue affects Raman bone quality measurements

    PubMed Central

    McElderry, John-David P.; Kole, Matthew R.; Morris, Michael D.

    2011-01-01

    The ability to probe fresh tissue is a key feature to biomedical Raman spectroscopy. However, it is unclear how Raman spectra of calcified tissues are affected by freezing. In this study, six transverse sections of femoral cortical bone were subjected to multiple freeze/thaw cycles and probed using a custom Raman microscope. Significant decreases were observed in the amide I and amide III bands starting after two freeze thaw cycles. Raman band intensities arising from proline residues of frozen tissue appeared consistent with fresh tissue after four cycles. Crystallinity values of bone mineral diminished slightly with freezing and were noticeable after only one freezing. Mineral carbonate levels did not deviate significantly with freezing and thawing. The authors recommend freezing and thawing bone tissue only once to maintain accurate results. PMID:21806253

  4. Development of osteogenic cell sheets for bone tissue engineering applications.

    PubMed

    Pirraco, Rogério P; Obokata, Haruko; Iwata, Takanori; Marques, Alexandra P; Tsuneda, Satoshi; Yamato, Masayuki; Reis, Rui L; Okano, Teruo

    2011-06-01

    The use of scaffolds in combination with osteogenic cells has been the gold standard in bone tissue engineering strategies. These strategies have, however, in many cases failed to produce the desired results due to issues such as the immunogenicity of the biomaterials used and cell necrosis at the bulk of the scaffold related to deficient oxygen and nutrients diffusion. Here, we originally propose the use of cell sheet (CS) engineering as a possible way to overcome some of these obstacles. Osteogenic CSs were fabricated by culturing rat bone marrow stromal cells in thermoresponsive culture dishes. The CSs were recovered from the dishes using a low-temperature treatment and then were implanted subcutaneously in nude mice. New bone formation was verified from day 7 post-transplantation using X-ray, microcomputed tomography, and histological analysis. The presence of a vascularized marrow was also verified in the newly formed bone after 6 weeks of transplantation. Further, osteocytes were found in this newly formed tissue, supporting the conclusion that mature bone was formed after ectopically transplanting osteogenic CSs. These results therefore confirm the great potentiality of CS engineering to be used in bone tissue engineering applications.

  5. Strontium- and zinc-alginate hydrogels for bone tissue engineering.

    PubMed

    Place, Elsie S; Rojo, Luis; Gentleman, Eileen; Sardinha, José P; Stevens, Molly M

    2011-11-01

    The development of bone replacement materials is an important healthcare objective due to the drawbacks of treating defects with bone autografts. In this work we propose a bone tissue engineering approach in which arginine-glycine-aspartic acid (RGD)-modified alginate hydrogels are crosslinked with bioactive strontium and zinc ions as well as calcium. Strontium was chosen for its ability to stimulate bone formation, and zinc is essential for alkaline phosphatase (ALP) activity. Calcium and strontium gels had similar stiffnesses but different stabilities over time. Strontium gels made with alginate with a high percentage of guluronic acid residues (high G) were slow to degrade, whereas those made with alginate rich in mannuronic acid (high M) degraded more quickly, and supported proliferation of Saos-2 osteoblast-like cells. After an initial burst, strontium release from alginate gels was steady and sustained, and the magnitude of release from high M gels was biologically relevant. Saos-2 cultured within alginate gels upregulated the osteoblast phenotypic marker genes RUNX2, collagen I (COL1A1) and bone sialoprotein (BSP), and ALP protein activity was highest in alginate gels cast with strontium ions. This strategy has the potential to be combined with other alginate-based systems for bone tissue engineering, or adapted to other tissue engineering applications.

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

    NASA Astrophysics Data System (ADS)

    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

  7. Challenges in engineering osteochondral tissue grafts with hierarchical structures.

    PubMed

    Gadjanski, Ivana; Vunjak-Novakovic, Gordana

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

    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. PMID:23576648

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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.

  12. Bone tissue engineering and regeneration: from discovery to the clinic--an overview.

    PubMed

    O'Keefe, Regis J; Mao, Jeremy

    2011-12-01

    A National Institutes of Health sponsored workshop "Bone Tissue Engineering and Regeneration: From Discovery to the Clinic" gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. © Mary Ann Liebert, Inc.

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

    PubMed

    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.

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

    PubMed

    Mijiritsky, Eitan; Ferroni, Letizia; Gardin, Chiara; Bressan, Eriberto; Zanette, Gastone; Piattelli, Adriano; Zavan, Barbara

    2017-09-08

    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.

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

    PubMed

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

    2013-05-21

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

  16. Bone tissue engineering and repair by gene therapy.

    PubMed

    Betz, Volker M; Betz, Oliver B; Harris, Mitchel B; Vrahas, Mark S; Evans, Christopher H

    2008-01-01

    Many clinical conditions require the stimulation of bone growth. The use of recombinant bone morphogenetic proteins does not provide a satisfying solution to these conditions due to delivery problems and high cost. Gene therapy has emerged as a very promising approach for bone repair that overcomes limitations of protein-based therapy. Several preclinical studies have shown that gene transfer technology has the ability to deliver osteogenic molecules to precise anatomical locations at therapeutic levels for sustained periods of time. Both in-vivo and ex-vivo transduction of cells can induce bone formation at ectopic and orthotopic sites. Genetic engineering of adult stem cells from various sources with osteogenic genes has led to enhanced fracture repair, spinal fusion and rapid healing of bone defects in animal models. This review describes current viral and non-viral gene therapy strategies for bone tissue engineering and repair including recent work from the author's laboratory. In addition, the article discusses the potential of gene-enhanced tissue engineering to enter widespread clinical use.

  17. Mesenchymal stem cells and alginate microcarriers for craniofacial bone tissue engineering: A review.

    PubMed

    Saltz, Adam; Kandalam, Umadevi

    2016-05-01

    Craniofacial bone is a complex structure with an intricate anatomical and physiological architecture. The defects that exist in this region therefore require a precise control of osteogenesis in their reconstruction. Unlike traditional surgical intervention, tissue engineering techniques mediate bone development with limited postoperative risk and cost. Alginate stands as the premier polymer in bone repair because of its mild ionotropic gelation and excellent biocompatibility, biodegradability, and injectability. Alginate microcarriers are candidates of choice to mediate cells and accommodate into 3-D environment. Several studies reported the use of alginate microcarriers for delivering cells, drugs, and growth factors. This review will explore the potential use of alginate microcarrier for stem cell systems and its application in craniofacial bone tissue engineering.

  18. Technical report: immunofluorescence and TUNEL staining of celloidin embedded human temporal bone tissues.

    PubMed

    Markaryan, Adam; Nelson, Erik G; Tretiakova, Maria; Hinojosa, Raul

    2008-07-01

    The large archival human temporal bone collections of the world have been fixed in formalin and embedded in celloidin. These treatments have created challenges to the use of contemporary probes, which are routinely used in the evaluation of fresh and frozen tissues, for the analysis of archival temporal bone tissues. Formalin alters the configuration of proteins and can obscure antigens by modifying the epitopes recognized by antibodies. Celloidin embedding provides superior support of the delicate membranous structures of the inner ear to maintain tissue integrity during sectioning, however, inadequate removal of celloidin may limit tissue permeability resulting in poor penetration of large molecules. Methods are described in this manuscript that have allowed reproducible immunofluorescence and TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labeling) staining results in these archival tissues. To our knowledge, successful immunofluorescence staining of type I collagen, immunofluorescence staining of cytochrome c oxidase subunit III (COX III), and TUNEL staining in archival human temporal bone tissues with confocal microscopy has not been previously reported. These results demonstrate the utility of developing techniques to evaluate the existing collections of archival temporal bones which remain our greatest source of tissue for investigating the causes of ear diseases.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  20. Ultrastructural elastic deformation of cortical bone tissue probed by NIR Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Finney, William F.; Morris, Michael D.; Wallace, Joseph M.; Kohn, David H.

    2004-07-01

    Raman spectroscopy is used as a probe of ultrastructural (molecular) changes in both the mineral and matrix (protein and glycoprotein, predominantly type I collagen) components of murine cortical bone as it responds to loading in the elastic regime. At the ultrastructural level, crystal structure and protein secondary structure distort as the tissue is loaded. These structural changes are followed as perturbations to tissue spectra. We load tissue in a custom-made dynamic mechanical tester that fits on the stage of a Raman microprobe and can accept hydrated tissue specimens. As the specimen is loaded in tension and/or compression, the shifts in mineral P-O4 v1 and relative band heights in the Amide III band envelope are followed with the microprobe. Average load is measured using a load cell while the tissue is loaded under displacement control. Changes occur in both the mineral and matrix components of bone as a response to elastic deformation. We propose that the mineral apatitic crystal lattice is deformed by movement of calcium and other ions. The matrix is proposed to respond by deformation of the collagen backbone. Raman microspectroscopy shows that bone mineral is not a passive contributor to tissue strength. The mineral active response to loading may function as a local energy storage and dissipation mechanism, thus helping to protect tissue from catastrophic damage.

  1. Compact biomedical pulsed signal generator for bone tissue stimulation

    DOEpatents

    Kronberg, J.W.

    1993-06-08

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

  2. Compact biomedical pulsed signal generator for bone tissue stimulation

    SciTech Connect

    Kronberg, James W.

    1993-01-01

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

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

    PubMed

    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 < 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. The protein diet promotes significant bone change on femur and in the hormones levels related to bone synthesis and maintenance of this tissue.

  4. Quantification of spatial structure of human proximal tibial bone biopsies using 3D measures of complexity

    NASA Astrophysics Data System (ADS)

    Saparin, Peter I.; Skovhus Thomsen, Jesper; Prohaska, Steffen; Zaikin, Alexei; Kurths, Jürgen; Hege, Hans-Christian; Gowin, Wolfgang

    2005-05-01

    Changes in trabecular bone composition during development of osteoporosis are used as a model for bone loss in microgravity conditions during a space flight. Symbolic dynamics and measures of complexity are proposed and applied to assess quantitatively the structural composition of bone tissue from 3D data sets of human tibia bone biopsies acquired by a micro-CT scanner. In order to justify the newly proposed approach, the measures of complexity of the bone architecture were compared with the results of traditional 2D bone histomorphometry. The proposed technique is able to quantify the structural loss of the bone tissue and may help to diagnose and to monitor changes in bone structure of patients on Earth as well as of the space-flying personnel.

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

    PubMed

    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.

  6. Neoplastic fever in patients with bone and soft tissue sarcoma

    PubMed Central

    Nakamura, Tomoki; Matsumine, Akihiko; Matsubara, Takao; Asanuma, Kunihiro; Sudo, Akihiro

    2016-01-01

    The development of fever is a common complication in the clinical course of cancer. If all other potential causes of fever are excluded, the possibility of neoplastic fever should be considered. The aim of the present study was to determine the incidence of neoplastic fever in patients with bone and soft tissue sarcomas. Between January 2009 and December 2014, 195 patients with bone and soft tissue sarcoma (111 men and 84 women; mean age, 55 years) were admitted to the Department of Orthopaedic Surgery of Mie University Graduate School of Medicine (Tsu, Japan). Episodes of fever were observed in 58 patients (30%), of whom 11 (5.5%) had neoplastic fever (mean maximum temperature, 38.9°C). The causes of neoplastic fever were as follows: Primary tumor (n=3), local recurrence (n=1), metastasis (n=5), and local recurrence with metastasis (n=2). Of the 11 patients, 9 were treated with naproxen and 8 exhibited a complete response, with their temperature normalizing to <37.3°C within 24 h. The 2 patients who were not treated with naproxen underwent surgical tumor resection, which resulted in prompt and complete lysis of the fever. In conclusion, neoplastic fever occurred in 5.5% of the 195 patients with bone and soft tissue sarcomas investigated herein. Naproxen may be effective for treating neoplastic fever in patients with bone and soft tissue sarcoma; however, radical tumor treatment may have to be considered to achieve permanent lysis of the fever. PMID:27900101

  7. Mineralization of human bone tissue under hypokinesia and physical exercise with calcium supplements

    NASA Astrophysics Data System (ADS)

    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 < 0.01 in both groups of men. A comparison between bone density changes in the control and experimental groups of men failed to demonstrate significant differences. It was concluded that the level of mineralization of bone tissues decreased under hypokinesia and physical exercise with calcium supplements. Experimental studies of hypokinetic physiology are generally based on the assumption that diminished muscular activity (progressive reduction of number of steps per day) is detrimental to animal and 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.

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

    PubMed Central

    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

  9. Bone tissue engineering bioreactors: a role in the clinic?

    PubMed

    Salter, Erin; Goh, Brian; Hung, Ben; Hutton, Daphne; Ghone, Nalinkanth; Grayson, Warren L

    2012-02-01

    Tissue engineered bone grafts have the potential to be used to treat large bone defects due to congenital abnormalities, cancer resections, or traumatic incidents. Recent studies have shown that perfusion bioreactors can be used to generate grafts of clinically relevant sizes and shapes. Despite these scientific and technological successes, there is uncertainty regarding the translational utility of bioreactor-based approaches due to the perceived high costs associated with these procedures. In fact, experiences over the past two decades have demonstrated that the widespread application of cell-based therapies is heavily dependent on the commercial viability. In this article, we directly address the question of whether bioreactors used to create bone grafts have the potential to be implemented in clinical approaches to bone repair and regeneration. We provide a brief review of tissue engineering approaches to bone repair, clinical trials that have employed cell-based methods, and advances in bioreactor technologies over the past two decades. These analyses are combined to provide a perspective on what is missing from the scientific literature that would enable an objective baseline for weighing the benefit of extended in vitro cultivation of cells into functional bone grafts against the cost of additional cultivation. In our estimation, the cost of bioreactor-based bone grafts may range from $10,000 to $15,000, placing it within the range of other widely used cell-based therapies. Therefore, in situations where a clear advantage can be established for engineered grafts comprising patient-specific, autologous cells, engineered bone grafts may be a clinically feasible option.

  10. In situ strategy for bone repair by facilitated endogenous tissue engineering.

    PubMed

    Chen, Jingdi; Zhang, Yujue; Pan, Panpan; Fan, Tiantang; Chen, Mingmao; Zhang, Qiqing

    2015-11-01

    Traditional tissue engineering procedures are expensive and time consuming. Facilitated endogenous tissue engineering (FETE) provides a solution that can avoid the ex vivo culture of autologous cells and initiate in situ reparative endogenous repair processes in vivo. This method involves fabricating a porous scaffold that mimics the environment present during the bone formation process, consisting of components that provide biomimetic interfacial interactions to cells. After the scaffold is implanted, progenitor cells provided by autologous bone marrow and surrounding tissues then differentiate to bone cells under the direction of the in situ scaffold. This paper reports a biomimetic method to prepare a hierarchically structured hybrid scaffold. Bone-like nano hydroxyapatite (HA) was crystallized from a collagen and chitosan (CC) matrix to form a porous scaffold. The in vivo study demonstrates that this nanohybrid scaffold supports excellent bone repair. This means that the FETE approach, in which the cell culture portion of traditional tissue engineering takes place in vivo, can promote the intrinsic regenerative potential of endogenous tissues.

  11. Fine structure of bone in dinosaurs, birds and mammals.

    PubMed

    Rensberger, J M; Watabe, M

    2000-08-10

    After observation of detailed structural evidence for the origin of birds from dinosaurs, and in light of evidence that dinosaur bone tissue resembles the histology in mammals, the histology of bone has become one of the focal points in discussions of the physiology of dinosaurs and Mesozoic birds. Most of this microstructural information has focused on features related to the vascular organization and the amount of remodelled bone around vascular canals. However, the finer structures have received less attention, although differences in such structures have been observed among modern vertebrates. Here we present evidence that canaliculi--the submicrometre-sized channels that interconnect bone cells and vascular canals--and the collagen fibre bundles in bone are differently organized among certain dinosaur lineages. Ornithomimid dinosaurs are more like birds than mammals in these features. In canalicular structure, and to some extent in fibre bundle arrangement, ornithischian dinosaurs are more like mammals. These differences in both canalicular and lamellar structure are probably linked to differences in the process and rate of bone formation.

  12. Fabrication and characterization of strontium incorporated 3-D bioactive glass scaffolds for bone tissue from biosilica.

    PubMed

    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.

  13. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    PubMed

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  14. Biopolymer/Calcium phosphate scaffolds for bone tissue engineering.

    PubMed

    Li, Jianhua; Baker, Bryan A; Mou, Xiaoning; Ren, Na; Qiu, Jichuan; Boughton, Robert I; Liu, Hong

    2014-04-01

    With nearly 30 years of progress, tissue engineering has shown promise in developing solutions for tissue repair and regeneration. Scaffolds, together with cells and growth factors, are key components of this development. Recently, an increasing number of studies have reported on the design and fabrication of scaffolding materials. In particular, inspired by the nature of bone, polymer/ceramic composite scaffolds have been studied extensively. The purpose of this paper is to review the recent progress of the naturally derived biopolymers and the methods applied to generate biomimetic biopolymer/calcium phosphate composites as well as their biomedical applications in bone tissue engineering. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Combination of negative pressure wound therapy with open bone grafting for bone and soft tissue defects.

    PubMed

    Deng, Kai; Yu, Ai-Xi; Xia, Cheng-Yan; Li, Zong-Huan; Wang, Wei-Yang

    2013-08-01

    The aim of this study was to investigate the efficiency of negative pressure wound therapy (NPWT) combined with open bone graft (OBG; NPWT-OBG) for the treatment of bone and soft tissue defects with polluted wounds in an animal model. All rabbits with bone and soft tissue defects and polluted wounds were randomly divided into two groups, the experimental group (NPWT with bone graft) and the control group (OBG). The efficacy of the treatment was assessed by the wound conditions and healing time. Bacterial bioburdens and bony calluses were evaluated by bacteria counting and X-rays, respectively. Furthermore, granulation tissue samples from the wounds on days 0, 3, 7 and 14 of healing were evaluated for blood vessels and vascular endothelial growth factor (VEGF) levels. Wounds in the experimental group tended to have a shorter healing time, healthier wound conditions, lower bacterial bioburden, improvement of the bony calluses and an increased blood supply compared with those in the control group. With NPWT, wound infection was effectively controlled. For wounds with osseous and soft tissue defects, NPWT combined with bone grafting was demonstrated to be more effective than an OBG.

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

    PubMed

    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.

  18. Quantitative polarized Raman spectroscopy in highly turbid bone tissue

    PubMed Central

    Raghavan, Mekhala; Sahar, Nadder D.; Wilson, Robert H.; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H.; Morris, Michael D.

    2010-01-01

    Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim∕oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim∕oim bones (28±3 deg) compared to wild-type bones (22±3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76±2 deg and in oim∕oim mice, it is 72±4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy. PMID:20615030

  19. Quantitative polarized Raman spectroscopy in highly turbid bone tissue

    NASA Astrophysics Data System (ADS)

    Raghavan, Mekhala; Sahar, Nadder D.; Wilson, Robert H.; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H.; Morris, Michael D.

    2010-05-01

    Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim/oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim/oim bones (28+/-3 deg) compared to wild-type bones (22+/-3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76+/-2 deg and in oim/oim mice, it is 72+/-4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

  20. Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma?

    PubMed Central

    Holzapfel, Boris Michael; Chhaya, Mohit Prashant; Melchels, Ferry Petrus Wilhelmus; Holzapfel, Nina Pauline; Prodinger, Peter Michael; von Eisenhart-Rothe, Ruediger; van Griensven, Martijn; Schantz, Jan-Thorsten; Rudert, Maximilian; Hutmacher, Dietmar Werner

    2013-01-01

    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. PMID:23509421

  1. The Pathology of Bone Tissue during Peri-Implantitis

    PubMed Central

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

    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 peri-implantitis bone tissue compared with healthy peri-implant bone tissue. Furthermore, cells from the osteoblastic lineage derived from peri-implantitis samples were immortalized and characterized. We applied microarray, quantitative reverse transcription polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. The levels of typical bone matrix molecules, including SPP1, BGLAP, and COL9A1, in patients with peri-implantitis were reduced, while the inflammation marker interleukin 8 (IL8) was highly expressed. RUNX2, one of the transcription factors of mature osteoblasts, was also decreased in peri-implantitis. Finally, the human telomerase reverse transcriptase immortalized cell line from peri-implantitis exhibited a more fibro-osteoblastic character than did the healthy control. PMID:25406169

  2. The pathology of bone tissue during peri-implantitis.

    PubMed

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

    2015-02-01

    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 peri-implantitis bone tissue compared with healthy peri-implant bone tissue. Furthermore, cells from the osteoblastic lineage derived from peri-implantitis samples were immortalized and characterized. We applied microarray, quantitative reverse transcription polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. The levels of typical bone matrix molecules, including SPP1, BGLAP, and COL9A1, in patients with peri-implantitis were reduced, while the inflammation marker interleukin 8 (IL8) was highly expressed. RUNX2, one of the transcription factors of mature osteoblasts, was also decreased in peri-implantitis. Finally, the human telomerase reverse transcriptase immortalized cell line from peri-implantitis exhibited a more fibro-osteoblastic character than did the healthy control. © International & American Associations for Dental Research 2014.

  3. Novel biodegradable three-dimensional macroporous scaffold using aligned electrospun nanofibrous yarns for bone tissue engineering.

    PubMed

    Cai, You-Zhi; Zhang, Guo-Rong; Wang, Lin-Lin; Jiang, Yang-Zi; Ouyang, Hong-Wei; Zou, Xiao-Hui

    2012-05-01

    This study aimed to develop a practical three-dimensional (3D) macroporous scaffold from aligned electrospun nanofibrous yarns for bone tissue engineering. A novel 3D unwoven macroporous nanofibrous (MNF) scaffold was manufactured with electrospun poly(L-lactic acid) and polycaprolactone (w/w 9:1) nanofibers through sequential yarns manufacture and honeycombing process at 65°C. The efficacy of 3D MNF scaffold for bone formation were evaluated using human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) differentiation model and rabbit tibia bone defect model. In vitro, more cell proliferation and cell ingrowth were observed in 3D MNF scaffold. Moreover, calcium deposit was obviously detected in vitro differentiation of hESC-MSCs. In vivo, histology and X-ray showed that 3D MNF scaffold treated bone defect had fine 3D bony tissue formation around the scaffold as well as inside the scaffold at 3 weeks and 6 weeks. This study demonstrated that 3D MNF scaffold provides a structural support for hESC-MSCs growth and guides bone formation suggesting that this novel strategy successfully makes use of electrospun fibers for bone tissue engineering, which may help realize the clinical translation of electrospun nanofibers for regenerative medicine in future.

  4. Perspectives on the Role of Nanotechnology in Bone Tissue Engineering

    PubMed Central

    Saiz, Eduardo; Zimmermann, Elizabeth A.; Lee, Janice S.; Wegst, Ulrike G.K.; Tomsia, Antoni P.

    2013-01-01

    Objective This review surveys new developments in bone tissue engineering, specifically focusing on the promising role of nanotechnology and describes future avenues of research. Methods The review first reinforces the need to fabricate scaffolds with multi-dimensional hierarchies for improved mechanical integrity. Next, new advances to promote bioactivity by manipulating the nano-level internal surfaces of scaffolds are examined followed by an evaluation of techniques to using scaffolds as a vehicle for local drug delivery to promote bone regeneration/integration and methods of seeding cells into the scaffold. Results Through a review of the state of the field, critical questions are posed to guide future research towards producing materials and therapies to bring state-of-the-art technology to clinical settings. Significance The development of scaffolds for bone regeneration requires a material able to promote rapid bone formation while possessing sufficient strength to prevent fracture under physiological loads. Success in simultaneously achieving mechanical integrity and sufficient bioactivity with a single material has been limited. However, the use of new tools to manipulate and characterize matter down to the nano-scale may enable a new generation of bone scaffolds that will surpass the performance of autologous bone implants. PMID:22901861

  5. Prefabricated vascularized bone flap: a tissue transformation technique for bone reconstruction.

    PubMed

    Alam, M I; Asahina, I; Seto, I; Oda, M; Enomoto, S

    2001-09-15

    In this study, an attempt was made to transform a muscle vascularized pedicle raised on host vessels into a vascularized bone flap, using recombinant human bone morphogenetic protein 2 (rhBMP-2). The purpose of this study was to produce new bone vascularized in nature to increase the survival rate of the subsequently grafted bone and to fabricate the newly formed bone into the desired shape. Silicone molds in the shape of a rat mandible were used to deliver rat bone matrix impregnated with or without rhBMP-2. A muscle pedicle the same size as the mold was raised on the saphenous vessels in the rat thigh and then sandwiched in the center of the silicone molds. The molds were sliced in half and each section was filled with rat bone matrix that was impregnated either with 25 microg of rhBMP-2 for the experimental group or with diluting material alone for the control group. The sandwiched flaps were then secured by tying them to the adjacent muscles and were harvested at 2 and 4 weeks after surgery. Three and six rats were used in the control and experimental groups at each time point, respectively. Bone formation was assessed in the ex vivo specimens by macroscopic, radiologic, and histologic evaluation. Macroscopically, the continuation of the vascular pedicle was clearly visible for both the control and experimental muscle flaps. However, no evidence of muscle-tissue transformation was observed in the control flaps, whereas all the flaps treated with rhBMP-2 produced new bone that replicated the shape of the mold exactly and had saphenous vessels supplying the newly formed bone. This study demonstrates that this experimental model has the potential to be therapeutically applied for effective bone reconstruction.

  6. The influence of environmental factors on bone tissue engineering.

    PubMed

    Szpalski, Caroline; Sagebin, Fabio; Barbaro, Marissa; Warren, Stephen M

    2013-05-01

    Bone repair and regeneration are dynamic processes that involve a complex interplay between the substrate, local and systemic cells, and the milieu. Although each constituent plays an integral role in faithfully recreating the skeleton, investigators have long focused their efforts on scaffold materials and design, cytokine and hormone administration, and cell-based therapies. Only recently have the intangible aspects of the milieu received their due attention. In this review, we highlight the important influence of environmental factors on bone tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

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

    PubMed

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

    2017-09-11

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

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

    PubMed

    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.

  9. [The application and advancement of rapid prototyping technology in bone tissue engineering].

    PubMed

    He, Chuanglong; Xia, Liewen; Luo, Yanfeng; Wang, Yuanliang

    2004-10-01

    In bone tissue engineering, a highly porous artificial extracellular matrix or scaffold is essential to the attachment, proliferation and differentiation of bone cells (osteoblast, osteoclast and osteocytes) and the formation of bone tissue. However, conventional scaffold materials for bone tissue engineering proved less valuable for actual applications because they lack mechanical strength, interconnected channel network, and controllable porosity or channel size. Therefore,to explore the ideal scaffold materials is one of the popular studies on current bone tissue engineering. In this paper, we review, the application and advancement of a newly-developed technology generally known as rapid prototyping (RP) techniques in bone tissue engineering.

  10. Paper-based bioactive scaffolds for stem cell-mediated bone tissue engineering.

    PubMed

    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.

  11. Multiscale FE method for analysis of bone micro-structures.

    PubMed

    Podshivalov, L; Fischer, A; Bar-Yoseph, P Z

    2011-08-01

    Bones are composed of hierarchical bio-composite materials characterized by complex multiscale structural geometry and behavior. The architecture and the mechanical properties of bone tissue differ at each level of hierarchy. Thus, a multiscale approach for mechanical analysis of bone is imperative. This paper proposes a new approach for 3D multiscale finite element analysis of trabecular bone that can offer physicians a "digital magnifying glass" to facilitate continuous transition between macro- and micro-scales. The approach imitates the human ability to perceive details. That is, zooming-out from an object causes fewer details to be visible. As a result, the material appears to be smoother and more homogeneous. Zooming-in, in contrast, reveals additional details and material heterogeneity. Realization of the proposed approach requires synergy between a hierarchical geometric model for representing intermediate scales and a mechanical model for local material properties of bone tissue for each scale. The geometric model facilitates seamless and continuous bi-directional transition between macro- and micro-scales, while the mechanical model preserves the effective material properties. A 2D model of a simplified trabecular structure was implemented and analyzed in order to assess the feasibility of the proposed multiscale approach. The successful results of this model led to extending the method into 3D and analyzing real trabecular structures.

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

    PubMed

    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.

  13. Microfibril Orientation Dominates the Microelastic Properties of Human Bone Tissue at the Lamellar Length Scale

    PubMed Central

    Rupin, Fabienne; Raum, Kay; Peyrin, Françoise; Burghammer, Manfred; Saïed, Amena; Laugier, Pascal

    2013-01-01

    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. PMID:23472132

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

    Mkhabela, Vuyiswa J.; Ray, Suprakas Sinha

    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.

  16. Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue.

    PubMed

    Judex, Stefan; Boyd, Steve; Qin, Yi-Xian; Miller, Lisa; Müller, Ralph; Rubin, Clinton

    2003-06-01

    Atraumatic fractures of the skeleton in osteoporotic patients are directly related to a deterioration of bone strength. However, the failure of the bone tissue to withstand functional load bearing cannot be explained as a simple decrease in bone mineral density (quantity); strength is also significantly dependent upon bone quality. While a formal definition of bone quality is somewhat elusive, at the very least, it incorporates architectural, physical, and biologic factors that are critical to bone strength. Such factors include bone morphology (ie, trabecular connectivity, cross-sectional geometry, longitudinal curvature); the tissue's material properties (eg, stiffness, strength); its chemical composition and architecture (eg, ratio of calcium to other components of the organic and/or inorganic phase, collagen orientation, porosity, permeability); and the viability of the tissue (eg, responsivity of the bone cell population). Combining high-resolution structural indices of bone, as determined by micro-computed tomography; material properties determined by nanoindentation; and the chemical make-up of bone, as determined by infrared spectroscopy, helps to provide critical information toward a more comprehensive assessment of the interdependence of bone quality, quantity, and fracture risk.

  17. Characteristics of Bone Tissue and Composite Materials on the Basis of Natural Hydroxyapatite and Endodontic Cement for Replacement of the Tissue

    NASA Astrophysics Data System (ADS)

    Filipenkov, V. V.; Rupeks, L. E.; Vitins, V. M.; Knets, I. V.; Kasyanov, V. A.

    2017-07-01

    New biocomposites and the cattle bone tissue were investigated. The composites were made from an endodontic cement (EC) and natural hydroxyapatite (NHAp.) The results of experiments performed by the method of infrared spectroscopy showed that protein was removed from the heat-treated specimens of bone tissue practically completely. The structure of bone tissue before and after deproteinization and the structure of the composite materials based on NHAp and EC (with different percentage) were investigated by the method of optical microscopy. The characteristics of mechanical properties (the initial elastic modulus, breaking tensile and compressive stresses, and breaking strain) and the density and porosity of these materials were determined. The new composite materials were implanted in the live tissue of rat. Biocompatibility between the live tissue and the new biocomposites was estimated.

  18. Remineralized Bone Matrix (RBM) as a Scaffold for Bone Tissue Engineering

    PubMed Central

    Soicher, Matthew A.; Christiansen, Blaine A.; Stover, Susan M.; Leach, J. Kent; Yellowley, Clare E.; Griffiths, Leigh G.; Fyhrie, David P.

    2014-01-01

    There is a need for improved biomaterials for use in treating non-healing bone defects. A number of natural and synthetic biomaterials have been used for the regeneration of bone tissue with mixed results. One approach is to modify native tissue via decellularization or other treatment for use as natural scaffolding for tissue repair. In this study, our goal was to improve on our previously published alternating solution immersion (ASI) method to fabricate a robust, biocompatible, and mechanically competent biomaterial from natural demineralized bone matrix (DBM). The improved method includes an antigen removal (AR) treatment step which improves mineralization and stiffness while removing unwanted proteins. The chemistry of the mineral in the remineralized bone matrix (RBM) was consistent with dicalcium phosphate dihydrate (brushite), a material used clinically in bone healing applications. Mass spectrometry identified proteins removed from the matrix with AR treatment to include α-2 HS-glycoprotein and osteopontin, non-collagenous proteins (NCPs) and known inhibitors of biomineralization. Additionally, the RBM supported the survival, proliferation, and differentiation of human mesenchymal stromal cells (MSCs) in vitro as well or better than other widely used biomaterials including DBM and PLG scaffolds. DNA content increased more than 10-fold on RBM compared to DBM and PLG; likewise, osteogenic gene expression was significantly increased after 1 and 2 weeks. We demonstrated that ASI remineralization has the capacity to fabricate mechanically stiff and biocompatible RBM, a suitable biomaterial for cell culture applications. PMID:24616346

  19. Preparation of Laponite Bioceramics for Potential Bone Tissue Engineering Applications

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    PubMed

    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.

  2. Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering.

    PubMed

    Chen, Zhuoyue; Song, Yue; Zhang, Jing; Liu, Wei; Cui, Jihong; Li, Hongmin; Chen, Fulin

    2017-03-01

    Electrospinning is an effective means to generate nano- to micro-scale polymer fibers resembling native extracellular matrix for tissue engineering. However, a major problem of electrospun materials is that limited pore size and porosity may prevent adequate cellular infiltration and tissue ingrowth. In this study, we first prepared thin layers of hydroxyapatite nanoparticle (nHA)/poly-hydroxybutyrate (PHB) via electrospinning. We then laminated the nHA/PHB thin layers to obtain a scaffold for cell seeding and bone tissue engineering. The results demonstrated that the laminated scaffold possessed optimized cell-loading capacity. Bone marrow mesenchymal stem cells (MSCs) exhibited better adherence, proliferation and osteogenic phenotypes on nHA/PHB scaffolds than on PHB scaffolds. Thereafter, we seeded MSCs onto nHA/PHB scaffolds to fabricate bone grafts. Histological observation showed osteoid tissue formation throughout the scaffold, with most of the scaffold absorbed in the specimens 2months after implantation, and blood vessels ingrowth into the graft could be observed in the graft. We concluded that electrospun and laminated nanoscaled biocomposite scaffolds hold great therapeutic potential for bone regeneration.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  5. Biodegradable Materials for Bone Repair and Tissue Engineering Applications

    PubMed Central

    Sheikh, Zeeshan; Najeeb, Shariq; Khurshid, Zohaib; Verma, Vivek; Rashid, Haroon; Glogauer, Michael

    2015-01-01

    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. PMID:28793533

  6. Massive osteoradionecrosis of facial bones and soft tissues.

    PubMed

    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.

  7. Silicates in orthopedics and bone tissue engineering materials.

    PubMed

    Zhou, Xianfeng; Zhang, Nianli; Mankoci, Steven; Sahai, Nita

    2017-07-01

    Following the success of silicate-based glasses as bioactive materials, silicates are believed to play important roles in promoting bone formation and have therefore been considered to provide a hydroxyapatite (HAP) surface layer capable of binding to bone as well as potentially being a pro-osteoinductive factor. Natural silicate minerals and silicate-substituted HAPs are also being actively investigated as orthopaedic bone and dental biomaterials for application in tissue engineering. However, the mechanisms for the proposed roles of silicate in these materials have not been fully understood and are controversial. Here, we review the potential roles of silicate for bone tissue engineering applications and recent breakthroughs in identifying the cellular-level molecular mechanisms for the osteoinductivity of silica. The goal of this article is to inspire new ideas for the rational design of third-generation cell-and gene-affecting biomaterials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2090-2102, 2017. © 2017 Wiley Periodicals, Inc.

  8. Biodegradable Materials for Bone Repair and Tissue Engineering Applications.

    PubMed

    Sheikh, Zeeshan; Najeeb, Shariq; Khurshid, Zohaib; Verma, Vivek; Rashid, Haroon; Glogauer, Michael

    2015-08-31

    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.

  9. Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration

    PubMed Central

    Zhang, Xingdi; Zeng, Deliang; Li, Nan; Wen, Jin; Jiang, Xinquan; Liu, Changsheng; Li, Yongsheng

    2016-01-01

    Mesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process. PMID:26763311

  10. Bone transplantation and tissue engineering, part III: allografts, bone grafting and bone banking in the twentieth century.

    PubMed

    Hernigou, Philippe

    2015-03-01

    During the 20th century, allograft implantation waned in popularity as a clinical activity. Reports appeared in the literature describing several small series of patients in whom bone was obtained from amputation specimens or recently deceased individuals. The concept of bone banking became a reality during and after World War II when the National Naval Tissue Bank was established in Bethesda and a number of small banks sprang up in hospitals throughout the world. Small fragments, either of cortical or medullary bone, from these banks were used heterotopically to augment spinal fusions, to implant into cyst cavities, or to serve as a scaffolding for repair of non- or delayed union of fractures of the long bones.

  11. Use of NASA Bioreactor in Engineering Tissue for Bone Repair

    NASA Technical Reports Server (NTRS)

    Duke, Pauline

    1998-01-01

    This study was proposed in search for a new alternative for bone replacement or repair. Because the systems commonly used in repair of bony defects form bone by going through a cartilaginous phase, implantation of a piece of cartilage could enhance the healing process by having a more advanced starting point. However, cartilage has seldom been used to replace bone due, in part, to the limitations in conventional culture systems that did not allow production of enough tissue for implants. The NASA-developed bioreactors known as STLV (Slow Turning Lateral Vessel) provide homogeneous distribution of cells, nutrients, and waste products, with less damaging turbulence and shear forces than conventional systems. Cultures under these conditions have higher growth rates, viability, and longevity, allowing larger "tissue-like" aggregates to form, thus opening the possibilities of producing enough tissue for implantation, along with the inherent advantages of in vitro manipulations. To assure large numbers of cells and to eliminate the use of timed embryos, we proposed to use an immortalized mouse limb bud cell line as the source of cells.

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

    PubMed

    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.

  13. Prospect of Stem Cells in Bone Tissue Engineering: A Review

    PubMed Central

    Yousefi, Azizeh-Mitra; James, Paul F.; Akbarzadeh, Rosa; Subramanian, Aswati; Flavin, Conor; Oudadesse, Hassane

    2016-01-01

    Mesenchymal stem cells (MSCs) have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) have been the focus of most studies due to the inherent potential of these cells to differentiate into various cell types. Although, the discovery of induced pluripotent stem cells (iPSCs) represents a paradigm shift in our understanding of cellular differentiation. These cells are another attractive stem cell source because of their ability to be reprogramed, allowing the generation of multiple cell types from a single cell. This paper briefly covers various types of stem cell sources that have been used for tissue engineering applications, with a focus on bone regeneration. Then, an overview of some recent studies making use of MSC-seeded 3D scaffold systems for bone tissue engineering has been presented. The emphasis has been placed on the reported scaffold properties that tend to improve MSCs adhesion, proliferation, and osteogenic differentiation outcomes. PMID:26880976

  14. Segmentation of bone CT images and assessment of bone structure using measures of complexity.

    PubMed

    Saparin, Peter; Thomsen, Jesper Skovhus; Kurths, Jürgen; Beller, Gisela; Gowin, Wolfgang

    2006-10-01

    A nondestructive and noninvasive method for numeric characterization (quantification) of the structural composition of human bone tissue has been developed and tested. In order to quantify and to compare the structural composition of bones from 2D computed tomography (CT) images acquired at different skeletal locations, a series of robust, versatile, and adjustable image segmentation and structure assessment algorithms were developed. The segmentation technique facilitates separation from cortical bone and standardizes the region of interest. The segmented images were symbol-encoded and different aspects of the bone structural composition were quantified using six different measures of complexity. These structural examinations were performed on CT images of bone specimens obtained at the distal radius, humeral mid-diaphysis, vertebral body, femoral head, femoral neck, proximal tibia, and calcaneus. In addition, the ability of the noninvasive and nondestructive measures of complexity to quantify trabecular bone structure was verified by comparing them to conventional static histomorphometry performed on human fourth lumbar vertebral bodies. Strong correlations were established between the measures of complexity and the histomorphometric parameters except for measures expressing trabecular thickness. Furthermore, the ability of the measures of complexity to predict vertebral bone strength was investigated by comparing the outcome of the complexity analysis of the CT images with the results of a biomechanical compression test of the third lumbar vertebral bodies from the same population as used for histomorphometry. A multiple regression analysis using the proposed measures including structure complexity index, structure disorder index, trabecular network index, index of a global ensemble, maximal L-block, and entropy of x-ray attenuation distribution revealed an excellent relationship (r=0.959, r2=0.92) between the measures of complexity and compressive bone strength

  15. Segmentation of bone CT images and assessment of bone structure using measures of complexity

    SciTech Connect

    Saparin, Peter; Thomsen, Jesper Skovhus; Kurths, Juergen; Beller, Gisela; Gowin, Wolfgang

    2006-10-15

    A nondestructive and noninvasive method for numeric characterization (quantification) of the structural composition of human bone tissue has been developed and tested. In order to quantify and to compare the structural composition of bones from 2D computed tomography (CT) images acquired at different skeletal locations, a series of robust, versatile, and adjustable image segmentation and structure assessment algorithms were developed. The segmentation technique facilitates separation of trabecular from cortical bone and standardizes the region of interest. The segmented images were symbol-encoded and different aspects of the bone structural composition were quantified using six different measures of complexity. These structural examinations were performed on CT images of bone specimens obtained at the distal radius, humeral mid-diaphysis, vertebral body, femoral head, femoral neck, proximal tibia, and calcaneus. In addition, the ability of the noninvasive and nondestructive measures of complexity to quantify trabecular bone structure was verified by comparing them to conventional static histomorphometry performed on human fourth lumbar vertebral bodies. Strong correlations were established between the measures of complexity and the histomorphometric parameters except for measures expressing trabecular thickness. Furthermore, the ability of the measures of complexity to predict vertebral bone strength was investigated by comparing the outcome of the complexity analysis of the CT images with the results of a biomechanical compression test of the third lumbar vertebral bodies from the same population as used for histomorphometry. A multiple regression analysis using the proposed measures including structure complexity index, structure disorder index, trabecular network index, index of a global ensemble, maximal L-block, and entropy of x-ray attenuation distribution revealed an excellent relationship (r=0.959, r{sup 2}=0.92) between the measures of complexity and

  16. Hybrid Hydroxyapatite Nanoparticle Colloidal Gels are Injectable Fillers for Bone Tissue Engineering

    PubMed Central

    Gu, Zhen; Jamal, Syed; Detamore, Michael S.

    2013-01-01

    Injectable bone fillers have emerged as an alternative to the invasive surgery often required to treat bone defects. Current bone fillers may benefit from improvements in dynamic properties such as shear thinning during injection and recovery of material stiffness after placement. Negatively charged inorganic hydroxyapatite (HAp) nanoparticles (NPs) were assembled with positively charged organic poly(d,l-lactic-co-glycolic acid) (PLGA) NPs to create a cohesive colloidal gel. This material is held together by electrostatic forces that may be disrupted by shear to facilitate extrusion, molding, or injection. Scanning electron micrographs of the dried colloidal gels showed a well-organized, three-dimensional porous structure. Rheology tests revealed that certain colloidal gels could recover after being sheared. Human umbilical cord mesenchymal stem cells were also highly viable when seeded on the colloidal gels. HAp/PLGA NP colloidal gels offer an attractive scheme for injectable filling and regeneration of bone tissue. PMID:23815275

  17. Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering.

    PubMed

    Denry, Isabelle; Kuhn, Liisa T

    2016-01-01

    Our goal is to review design strategies for the fabrication of calcium phosphate ceramic scaffolds (CPS), in light of their transient role in bone tissue engineering and associated requirements for effective bone regeneration. We examine the various design options available to meet mechanical and biological requirements of CPS and later focus on the importance of proper characterization of CPS in terms of architecture, mechanical properties and time-sensitive properties such as biodegradability. Finally, relationships between in vitro versus in vivo testing are addressed, with an attempt to highlight reliable performance predictors. A combinatory design strategy should be used with CPS, taking into consideration 3D architecture, adequate surface chemistry and topography, all of which are needed to promote bone formation. CPS represent the media of choice for delivery of osteogenic factors and anti-infectives. Non-osteoblast mediated mineral deposition can confound in vitro osteogenesis testing of CPS and therefore the expression of a variety of proteins or genes including collagen type I, bone sialoprotein and osteocalcin should be confirmed in addition to increased mineral content. CPS are a superior scaffold material for bone regeneration because they actively promote osteogenesis. Biodegradability of CPS via calcium and phosphate release represents a unique asset. Structural control of CPS at the macro, micro and nanoscale and their combination with cells and polymeric materials is likely to lead to significant developments in bone tissue engineering. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  18. Design and Characterization of Calcium Phosphate Ceramic Scaffolds for Bone Tissue Engineering

    PubMed Central

    Kuhn, Liisa T.

    2015-01-01

    Objectives Our goal is to review design strategies for the fabrication of calcium phosphate ceramic scaffolds (CPS), in light of their transient role in bone tissue engineering and associated requirements for effective bone regeneration. Methods We examine the various design options available to meet mechanical and biological requirements of CPS and later focus on the importance of proper characterization of CPS in terms of architecture, mechanical properties and time-sensitive properties such as biodegradability. Finally, relationships between in vitro vs. in vivo testing are addressed, with an attempt to highlight reliable performance predictors. Results A combinatory design strategy should be used with CPS taking into consideration 3D architecture, adequate surface chemistry and topography, all of which are needed to promote bone formation. CPS represent the media of choice for delivery of osteogenic factors and anti-infectives. Non-osteoblast mediated mineral deposition can confound in vitro osteogenesis testing of CPS and therefore the expression of a variety of proteins or genes including collagen type I, bone sialoprotein and osteocalcin should be confirmed in addition to increased mineral content. Conclusions CPS are a superior scaffold material for bone regeneration because they actively promote osteogenesis. Biodegradability of CPS via calcium and phosphate release represents a unique asset. Structural control of CPS at the macro, micro and nanoscale and their combination with cells and polymeric materials is likely to lead to significant developments in bone tissue engineering. PMID:26423007

  19. Processing nanoengineered scaffolds through electrospinning and mineralization suitable for biomimetic bone tissue engineering.

    PubMed

    Liao, Susan; Murugan, Ramalingam; Chan, Casey K; Ramakrishna, Seeram

    2008-07-01

    Processing scaffolds that mimic the extracellular matrix (ECM) of natural bone in structure and chemical composition is a potential promising option for engineering physiologically functional bone tissue. In this article, we report a novel method, by combining electrospinning and mineralization, to process a series of nano-fibrous scaffolding systems with desirable characteristics suitable for biomimetic bone tissue engineering. We have chosen two types of polymers, namely collagen and poly (lactic-co-glycolic acid) (PLGA), natural and synthetic of its kind, respectively, to electrospin into nano-fibrous scaffolds. The electrospun scaffolds have high surface area, high porosity and well connected open pore network. In order to mimic the chemical composition of native bone ECM, the electrospun scaffolds were subjected to mineralization under optimal conditions. From the experimental results, we observed that the formation of bone-like apatite into collagen was relatively abundant and significantly more uniform than PLGA. The major finding of this study has suggested that the surface functional groups of the scaffolding material, such as carboxyl and carbonyl groups of collagen, are important for the mineralization in vitro. In addition, this study revealed that the mineralization process predominantly induce the formation of nanosize carbonated hydroxyapatite (CHA) during collagen mineralization, whilst nanosize hydroxyapatite (HA) is formed during PLGA mineralization. These findings are critically important while selecting the material for processing bone scaffolding system.

  20. Natural marine sponges for bone tissue engineering: The state of art and future perspectives.

    PubMed

    Granito, Renata Neves; Custódio, Márcio Reis; Rennó, Ana Claudia Muniz

    2017-08-01

    Marine life and its rich biodiversity provide a plentiful resource of potential new products for the society. Remarkably, marine organisms still remain a largely unexploited resource for biotechnology applications. Among them, marine sponges are sessile animals from the phylum Porifera dated at least from 580 million years ago. It is known that molecules from marine sponges present a huge therapeutic potential in a wide range of applications mainly due to its antitumor, antiviral, anti-inflammatory, and antibiotic effects. In this context, this article reviews all the information available in the literature about the potential of the use of marine sponges for bone tissue engineering applications. First, one of the properties that make sponges interesting as bone substitutes is their structural characteristics. Most species have an efficient interconnected porous architecture, which allows them to process a significant amount of water and facilitates the flow of fluids, mimicking an ideal bone scaffold. Second, sponges have an organic component, the spongin, which is analogous to vertebral collagen, the most widely used natural polymer for tissue regeneration. Last, osteogenic properties of marine sponges is also highlighted by their mineral content, such as biosilica and other compounds, that are able to support cell growth and to stimulate bone formation and mineralization. This review focuses on recent studies concerning these interesting properties, as well as on some challenges to be overcome in the bone tissue engineering field. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1717-1727, 2017. © 2016 Wiley Periodicals, Inc.

  1. The use of bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.

    PubMed

    Kagami, Hideaki; Agata, Hideki; Inoue, Minoru; Asahina, Izumi; Tojo, Arinobu; Yamashita, Naohide; Imai, Kohzoh

    2014-06-01

    Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms.

  2. N-Glycan structures of an osteopontin from human bone.

    PubMed

    Masuda, K; Takahashi, N; Tsukamoto, Y; Honma, H; Kohri, K

    2000-02-24

    N-Glycan structures of osteopontin (a bone matrix protein) from human bone (lumbar vertabrate) are reported in detail. Asn-linked glycan portion was released from 100 microg of osteopontin by digestion with glycoamidase A (from sweet almond), and the reducing ends of the N-glycans were reductively aminated with 2-aminopyridine. The derivatized N-glycans were separated and structurally identified by a multidimensional mapping technique on HPLC columns. Two major N-glycan structures were also confirmed by mass spectrometry. The proposed structures are shown below. The result should permit future comparison with the N-glycan structures of osteopontins obtained from other sources (kidney tissues, macrophages, urinary stones, human milk, etc.).

  3. Biochemical and biophysical analyses of tissue-engineered bone obtained from three-dimensional culture of a subset of bone marrow mesenchymal stem cells.

    PubMed

    Ferro, Federico; Falini, Giuseppe; Spelat, Renza; D'Aurizio, Federica; Puppato, Elisa; Pandolfi, Maura; Beltrami, Antonio Paolo; Cesselli, Daniela; Beltrami, Carlo Alberto; Impiombato, Francesco Saverio Ambesi; Curcio, Francesco

    2010-12-01

    Grafts of tissue-engineered bone represent a promising alternative in the treatment of large and small bone defects. Current approaches are often badly tolerated by patients because of invasiveness, ethical problems, culture, and possibility of infection. Autologous grafts have been indicated as a solution to such problems. Because of tissue availability, many have proposed the use of cultured cells derived from bone marrow expanded in culture and induced to differentiate in bone tissue. Data reported in the literature show that it is possible to produce tissue substitutes in vitro indeed, but results are not always concordant regarding the in vitro produced bone quality. In the present work, we investigated bone formation in aggregates of human bone marrow-derived mesenchymal stem cells induced to differentiate in bone. After osteoinduction we characterized the mineral matrix produced using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and X-ray powder diffraction. Cells were obtained from bone marrow, subjected to immunodepletion for CD3, CD11b, CD14, CD16, CD19, CD56, CD66b, and glycophorin A using RosetteSep and cultured in a new formulation of medium for four passages and then were allowed to form spontaneous aggregates. At the end of proliferation before aggregation, cells were analyzed by fluorescent activated cell sorting (FACS) for markers routinely used to characterize expanded mesenchymal stem cells and were found to be remarkably homogeneous for CD29 (99% ± 1%), CD73 (99% ± 1%), CD90 (95% ± 4%), CD105 (96% ± 4%), and CD133 (0% ± 1%) expression. Our results show that not only aggregated cells express the major markers of osteogenic differentiation, such as osteocalcin, osteonectin, osteopontin, and bone sialoprotein, but also the inorganic matrix is made of an apatite structurally and morphologically similar to native bone even without a scaffold.

  4. The Treatment Efficacy of Bone Tissue Engineering Strategy for Repairing Segmental Bone Defects Under Osteoporotic Conditions.

    PubMed

    Wang, Zhen Xing; Chen, Cheng; Zhou, Quan; Wang, Xian Song; Zhou, Guangdong; Liu, Wei; Zhang, Zhi-Yong; Cao, Yilin; Zhang, Wen Jie

    2015-09-01

    The potential of increasing bone mass and preventing fractures in osteoporosis using stem cell therapy is currently an area of intense focus. However, there are very little data available regarding the postfracture bony defect healing efficacy under osteoporotic conditions. This study aims to investigate whether critical-sized segmental bone defects in a rabbit model of osteoporosis could be repaired using an allogenic stem cell-based tissue engineering (TE) approach and to investigate the potential influence of osteoporosis on the treatment efficacy. Rabbit fetal bone marrow mesenchymal stem cells (BMSCs) were harvested and expanded in vitro. Decalcified bone matrix (DBM) scaffolds were then seeded with allogenic fetal BMSCs and cultivated in osteogenic media to engineer BMSC/DBM constructs. Critical-sized radial defects were created in ovariectomized (OVX) rabbits and the defects were repaired either by insertion of BMSC/DBM constructs or by DBM scaffolds alone. Also, nonovariectomized age-matched (non-OVX) rabbits were served as control. At 3 months post-treatment under the osteoporotic condition (OVX rabbits), the BMSC/DBM constructs inserted within the defect generated significantly more bone tissue when compared to the DBM scaffold as demonstrated by the X-ray, microcomputed tomography, and histological analyses. In addition, when compared to a normal nonosteoporotic condition (age-matched non-OVX rabbits), the defect treatment efficacy was adversely affected by the osteoporotic condition with significantly less bone regeneration. This study demonstrated the potential of allogenic fetal BMSC-based TE strategy for repairing bone defects in an osteoporotic condition. However, the treatment efficacy could be considerably compromised in the OVX animals. Therefore, a more sophisticated strategy that addresses the complicated pathogenic conditions associated with osteoporosis is needed.

  5. Porous expandable device for attachment to bone tissue

    DOEpatents

    Rybicki, Edmund F.; Wheeler, Kenneth Ray; Hulbert, Lewis E.; Karagianes, Manuel Tom; Hassler, Craig R.

    1977-01-01

    A device for attaching to substantially solid living bone tissue, comprising a body member having an outer surface shaped to fit approximately into an empty space in the tissue and having pores into which the tissue can grow to strengthen the bond between the device and the tissue, and adjustable means for expanding the body member against the tissue to an extent such as to provide a compressive stress capable of maintaining a snug and stable fit and of enhancing the growth of the tissue into the pores in the body member. The expanding means is adjustable to provide a stress between the tissue and the body member in the range of about 150 to 750 psi, typically 150 to 350 psi. Typically the body member comprises an expandable cylindrical portion having at least one radial slit extending longitudinally from a first end to the vicinity of the opposite (second) end thereof, at least one radial slit extending longitudinally from the second end to the vicinity of the first end thereof, and a tapered cylindrical hole extending coaxially from a wider circular opening in the first end to a narrower circular opening communicating with the second end.

  6. Effect of microstructure on micromechanical performance of dry cortical bone tissues

    SciTech Connect

    Yin Ling; Venkatesan, Sudharshan; Kalyanasundaram, Shankar; Qin Qinghua

    2009-12-15

    The mechanical properties of bone depend on composition and structure. Previous studies have focused on macroscopic fracture behavior of bone. In the present study, we performed microindentation studies to understand the deformation properties and microcrack-microstructure interactions of dry cortical bone. Dry cortical bone tissues from lamb femurs were tested using Vickers indentation with loads of 0.245-9.8 N. We examined the effect of bone microstructure on deformation and crack propagation using scanning electron microscopy (SEM). The results showed the significant effect of cortical bone microstructure on indentation deformation and microcrack propagation. The indentation deformation of the dry cortical bone was basically plastic at any applied load with a pronounced viscoelastic recovery, in particular at lower loads. More microcracks up to a length of approximately 20 {mu}m occurred when the applied load was increased. At loads of 4.9 N and higher, most microcracks were found to develop from the boundaries of haversian canals, osteocyte lacunae and canaliculi. Some microcracks propagated from the parallel direction of the longitudinal interstitial lamellae. At loads 0.45 N and lower, no visible microcracks were observed.

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

    NASA Astrophysics Data System (ADS)

    Espinoza Orias, Alejandro A.

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

  8. (*) Fabrication and Characterization of Biphasic Silk Fibroin Scaffolds for Tendon/Ligament-to-Bone Tissue Engineering.

    PubMed

    Font Tellado, Sònia; Bonani, Walter; Balmayor, Elizabeth R; Foehr, Peter; Motta, Antonella; Migliaresi, Claudio; van Griensven, Martijn

    2017-08-01

    Tissue engineering is an attractive strategy for tendon/ligament-to-bone interface repair. The structure and extracellular matrix composition of the interface are complex and allow for a gradual mechanical stress transfer between tendons/ligaments and bone. Thus, scaffolds mimicking the structural features of the native interface may be able to better support functional tissue regeneration. In this study, we fabricated biphasic silk fibroin scaffolds designed to mimic the gradient in collagen molecule alignment present at the interface. The scaffolds had two different pore alignments: anisotropic at the tendon/ligament side and isotropic at the bone side. Total porosity ranged from 50% to 80% and the majority of pores (80-90%) were <100-300 μm. Young's modulus varied from 689 to 1322 kPa depending on the type of construct. In addition, human adipose-derived mesenchymal stem cells were cultured on the scaffolds to evaluate the effect of pore morphology on cell proliferation and gene expression. Biphasic scaffolds supported cell attachment and influenced cytoskeleton organization depending on pore alignment. In addition, the gene expression of tendon/ligament, enthesis, and cartilage markers significantly changed depending on pore alignment in each region of the scaffolds. In conclusion, the biphasic scaffolds fabricated in this study show promising features for tendon/ligament-to-bone tissue engineering.

  9. Permeability analysis of scaffolds for bone tissue engineering.

    PubMed

    Dias, M R; Fernandes, P R; Guedes, J M; Hollister, S J

    2012-04-05

    Porous artificial bone substitutes, especially bone scaffolds coupled with osteobiologics, have been developed as an alternative to the traditional bone grafts. The bone scaffold should have a set of properties to provide mechanical support and simultaneously promote tissue regeneration. Among these properties, scaffold permeability is a determinant factor as it plays a major role in the ability for cells to penetrate the porous media and for nutrients to diffuse. Thus, the aim of this work is to characterize the permeability of the scaffold microstructure, using both computational and experimental methods. Computationally, permeability was estimated by homogenization methods applied to the problem of a fluid flow through a porous media. These homogenized permeability properties are compared with those obtained experimentally. For this purpose a simple experimental setup was used to test scaffolds built using Solid Free Form techniques. The obtained results show a linear correlation between the computational and the experimental permeability. Also, this study showed that permeability encompasses the influence of both porosity and pore size on mass transport, thus indicating its importance as a design parameter. This work indicates that the mathematical approach used to determine permeability may be useful as a scaffold design tool.

  10. Role of trace elements (Zn, Sr, Fe) in bone development: energy dispersive X-ray fluorescence study of rat bone and tooth tissue.

    PubMed

    Maciejewska, Karina; Drzazga, Zofia; Kaszuba, Michał

    2014-01-01

    Osteoporosis is one of the most common debilitating disease around the world and it is more and more established among young people. There are well known recommendations for nutrition of newborns and children concerning adequate calcium and vitamin D intake in order to maintain proper bone density. Nevertheless, important role in structure and function of a healthy bone tissue is played by an integration between all constituents including elements other than Ca, like trace elements, which control vital processes in bone tissue. It is important from scientific point of view as well as prevention of bone diseases, to monitor the mineralization process considering changes of the concentration of minerals during first stage of bone formation. This work presents studies of trace element (zinc, strontium, and iron) concentration in bones and teeth of Wistar rats at the age of 7, 14, and 28 days. Energy dispersive X-ray fluorescence (EDXRF) was used to examine mandibles, skulls, femurs, tibiae, and incisors. The quantitative analysis was performed using fundamental parameters method (FP). Zn and Sr concentrations were highest for the youngest individuals and decreased with age of rats, while Fe content was stable in bone matrix for most studied bones. Our results reveal the necessity of monitoring concentration of not only major, but also minor elements, because the trace elements play special role in the first period of bone development.

  11. High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

    PubMed

    Babur, Betul Kul; Futrega, Kathryn; Lott, William B; Klein, Travis Jacob; Cooper-White, Justin; Doran, Michael Robert

    2015-09-01

    Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8-14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

  12. Conception on the cell mechanisms of bone tissue loss under spase flight conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia; Oganov, Victor; Kabitskaya, Olga

    Basing on the analysis of available literature and the results of our own electron microscopic and radioautographic researches the data are presented about the morpho-functional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures under normal conditions and after exposure of animals (rats, monkeys, mice) to microgravity (SLS-2, Bion-11, BionM-1). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and surface osteocytes as well as to the bone-marrow stromal cells and to those lying on bone surfaces. As a response to the mechanical stimulus (microgravity) the system of stromal cell-preosteoblast-osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, some of the osteoblasts undergo apoptosis. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts and bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process. However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn’t occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in these remodeling loci. These cell reactions are considered as adaptive-compensatory, but they don’t result

  13. Biodegradable nanofibers-reinforced microfibrous composite scaffolds for bone tissue engineering.

    PubMed

    Martins, Albino; Pinho, Elisabete D; Correlo, Vítor M; Faria, Susana; Marques, Alexandra P; Reis, Rui L; Neves, Nuno M

    2010-12-01

    Native bone extracellular matrix (ECM) is a complex hierarchical fibrous composite structure, resulting from the assembling of collagen fibrils at several length scales, ranging from the macro to the nanoscale. The combination of nanofibers within microfibers after conventional reinforcement methodologies seems to be a feasible solution to the rational design of highly functional synthetic ECM substitutes. The present work aims at the development of bone ECM inspired structures, conjugating electrospun chitosan (Cht) nanofibers within biodegradable polymeric microfibers [poly(butylene succinate)-PBS and PBS/Cht], assembled in a fiber mesh structure. The nanofibers-reinforced composite fiber mesh scaffolds were seeded with human bone marrow mesenchymal stem cells (hBMSCs) and cultured under osteogenic differentiation conditions. These nanofibers-reinforced composite scaffolds sustained ECM deposition and mineralization, mainly in the PBS/Cht-based fiber meshes, as depicted by the increased amount of calcium phosphates produced by the osteogenic differentiated hBMSCs. The osteogenic genotype of the cultured hBMSCs was confirmed by the expression of osteoblastic genes, namely Alkaline Phosphatase, Osteopontin, Bone Sialoprotein and Osteocalcin, and the transcription factors Runx2 and Osterix, all involved in different stages of the osteogenesis. These data represent the first report on the biological functionality of nanofibers-reinforced composite scaffolds, envisaging the applicability of the developed structures for bone tissue engineering.

  14. Solubility of Structurally Complicated Materials: II. Bone

    NASA Astrophysics Data System (ADS)

    Horvath, Ari L.

    2006-12-01

    Bone is a structurally complex material, formed of both organic and inorganic chemicals. The organic compounds constitute mostly collagen and other proteins. The inorganic or bone mineral components constitute predominantly calcium, phosphate, carbonate, and a host of minor ingredients. The mineralized bone is composed of crystals which are closely associated with a protein of which collagen is an acidic polysaccharide material. This association is very close and the protein integrates into the crystalline structure. The mineralization involves the deposition of relatively insoluble crystals on an organic framework. The solubility process takes place when the outermost ions in the crystal lattice breakaway from the surface and become separated from the crystal. This is characteristic for ions dissolving in water or aqueous solutions at the specified temperature. The magnitude of solubility is temperature and pH dependent. Bone is sparingly soluble in most solvents. Enamel is less soluble than bone and fluoroapatite is the least soluble of all apatites in acid buffers. Collagen is less soluble in neutral salt solution than in dilute acid solutions at ambient temperatures. The solubility of collagens in solvents gradually decreases with increasing age of the bone samples.

  15. Ethnic and sex differences in bone marrow adipose tissue and bone mineral density relationship

    PubMed Central

    Chen, J.; Gantz, M.; Punyanitya, M.; Heymsfield, S. B.; Gallagher, D.; Albu, J.; Engelson, E.; Kotler, D.; Pi-Sunyer, X.; Shapses, S.

    2012-01-01

    Summary The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. Introduction It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. Methods Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18–88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. Results A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r=−0.533, −0.576, respectively; P<0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premeno-pausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. Conclusions An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations. PMID

  16. Self-assembling peptide nanofibers coupled with neuropeptide substance P for bone tissue engineering.

    PubMed

    Kim, Su Hee; Hur, Woojune; Kim, Ji Eun; Min, Hye Jeong; Kim, Sukwha; Min, Hye Sook; Kim, Byeung Kyu; Kim, Soo Hyun; Choi, Tae Hyun; Jung, Youngmee

    2015-04-01

    The number of patients requiring flat bone transplantation continues to increase worldwide. Cell transplantation has been successfully applied clinically; however, it causes another defect site and the time requirements to harvest cells and expand them are considerable. In this study, KLD12/KLD12-SP (KLD12+KLD12-substance P [SP]) was designed to mimic endogenous tissue-healing processes. The structures of KLD12, KLD12-SP, and KLD12/KLD12-SP were observed by transmission electron microscopy and circular dichroism spectra. KLD12/KLD12-SP nanofibers (5-10 nm) were created under physiological conditions by formation of a β-sheet structure. The ability of mesenchymal stem cells (MSCs) to recruit KLD12/KLD12-SP was observed by using an in vivo fluorescence imaging system. Labeled human bone marrow stromal cells supplied via an intravenous injection were recruited to the scaffold containing KLD12/KLD12-SP. Polylactic acid/beta-tricalcium phosphate (PLA/β-TCP) scaffolds filled with KLD12/KLD12-SP were applied to repair calvarial defects. The composite constructs (groups: defect, PLA/β-TCP, PLA/β-TCP/KLD12, and PLA/β-TCP/KLD12/KLD12-SP) were implanted into rat defect sites. Bone tissue regeneration was evaluated by observing gross morphology by hematoxylin and eosin and Masson's trichrome staining at 12 and 24 weeks after surgery. Gross morphology showed that the defect site was filled with new tissue that was integrated with host tissue in the KLD12/KLD12-SP group. In addition, from the staining data, cells were recruited to the defect site and lacunae structures formed in the KLD12/KLD12-SP group. From these results, the PLA/β-TCP+KLD12/KLD12-SP composite construct was considered for enhancement of bone tissue regeneration without cell transplantation.

  17. [Bone Cell Biology Assessed by Microscopic Approach. Novel insights about bone tissue by new microscopy systems].

    PubMed

    Tsuboi, Kanako; Hasegawa, Tomoka; Hongo, Hiromi; Yurimoto, Hisayoshi; Kobayashi, Sachio

    2015-10-01

    The osteocytic cytoplasmic processes show regularly-arranged three-dimensional structure, a cellular network called osteocytic lacunar-canalicular system (OLCS). We have demonstrated the ultrastructure of the cellular network of OLCS by means of a structured illumination microscope method (SIM) and a Focused Ion Beam-Scanning Electron Microscope (FIB-SEM). We also attempted to localize exogenously-administered minodronate, a new generation of bisphosphonate, as well as calcium deposition onto the bone forming surface, using an isotope microscope system. Recent devised microscopic technique may provide new insights in the research field of bone.

  18. Core-shell fibrous stem cell carriers incorporating osteogenic nanoparticulate cues for bone tissue engineering.

    PubMed

    Olmos Buitrago, Jennifer; Perez, Roman A; El-Fiqi, Ahmed; Singh, Rajendra K; Kim, Joong-Hyun; Kim, Hae-Won

    2015-12-01

    Moldable hydrogels that incorporate stem cells hold great promise for tissue engineering. They secure the encapsulated cells for required periods while allowing a permeable exchange of nutrients and gas with the surroundings. Core-shell fibrous structured hydrogel system represents these properties relevant to stem cell delivery and defect-adjustable tissue engineering. A designed dual concentric nozzle is used to simultaneously deposit collagen and alginate with a core-shell structured continuous fiber form in the ionic calcium bath. We aimed to impart extrinsic osteogenic cues in the nanoparticulate form, i.e., bioactive glass nanoparticles (BGn), inside the alginate shell, while encapsulating rat mesenchymal stem cells in the collagen core. Ionic measurement in aqueous solution indicated a continuous release of calcium ions from the BGn-added and -free scaffolds, whereas silicon was only released from the BGn-containing scaffolds. The presence of BGn allowed higher number of cells to migrate into the scaffolds when implanted in subcutaneous tissues of rat. Cell viability was preserved in the presence of the BGn, with no significant differences noticed from the control. The presence of BGn enhanced the osteogenic differentiation of the encapsulated rat mesenchymal stem cells, presenting higher levels of alkaline phosphatase activity as well as bone related genes, including collagen type I, bone sialoprotein and osteocalcin. Taken together, the incorporated BGn potentiated the capacity of the core-shell fibrous hydrogel system to deliver stem cells targeting bone tissue engineering. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. Characterization of bone marrow mononuclear cells on biomaterials for bone tissue engineering in vitro.

    PubMed

    Henrich, Dirk; Verboket, René; Schaible, Alexander; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

    2015-01-01

    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.

  20. Reconstruction of large mandibular bone and soft-tissue defect using bone transport distraction osteogenesis.

    PubMed

    Elsalanty, Mohammed E; Taher, Taher N; Zakhary, Ibrahim E; Al-Shahaat, Osama A; Refai, Mohammed; El-Mekkawi, Hatem A

    2007-11-01

    Reconstruction of large anterior mandibular defects is a challenging task. The condition can become even more complex if primary reconstruction fails, leading to loss of the entire midline portion of the lower face with massive scarring of the remaining tissues. Bone transport distraction osteogenesis can provide a viable treatment option for these patients. One of such cases will be presented, followed by a discussion of the advantages, disadvantages, and limitations of the technique.

  1. The prospective opportunities offered by magnetic scaffolds for bone tissue engineering: a review

    PubMed Central

    ORTOLANI, ALESSANDRO; BIANCHI, MICHELE; MOSCA, MASSIMILIANO; CARAVELLI, SILVIO; FUIANO, MARIO; MARCACCI, MAURILIO; RUSSO, ALESSANDRO

    2016-01-01

    Magnetic scaffolds are becoming increasingly attractive in tissue engineering, due to their ability to enhance bone tissue formation by attracting soluble factors, such as growth factors, hormones and polypeptides, directly to the implantation site, as well as their potential to improve the fixation and stability of the implant. Moreover, there is increasing evidence that the synergistic effects of magnetic scaffolds and magnetic fields can promote bone repair and regeneration. In this manuscript we review the recent innovations in bone tissue engineering that exploit magnetic biomaterials combined with static magnetic fields to enhance bone cell adhesion and proliferation, and thus bone tissue growth. PMID:28217659

  2. Bone-demineralization diagnosis in a bone-tissue-skin matrix using the pulsed-chirped photothermal radar

    NASA Astrophysics Data System (ADS)

    Kaiplavil, Sreekumar; Mandelis, Andreas

    2012-02-01

    A chirped pulsed photothermal radiometric radar is introduced for the diagnosis of biological samples, especially bones with tissue and skin overlayers. The constraints imposed by the laser safety (maximum permissible exposure, MPE) ceiling on pump laser energy and the strong attenuation of thermal-wave signals in tissues significantly limit the photothermally active depth in most biological specimens to a level which is normally insufficient for practical applications (approx. 1 mm below the skin surface). A theoretical approach for improvement of signal-to-noise ratio (SNR), minimizing the static (dc) component of the photothermal signal and making use of the photothermal radiometric nonlinearity has been introduced and verified by comparing the SNR of four distinct excitation wave forms (sine-wave, square-wave, constant- width and constant duty-cycle pulses) for chirping the pump laser, under constant exposure energy. At low frequencies fixed-pulsewidth chirps of large peak power were found to be superior to all other equal-energy modalities, with an SNR improvement up to two orders of magnitude. Distinct thickness-dependent characteristic delay times in a goat bone were obtained, establishing an active depth resolution range of ca. 2.8 mm in a layered skin-fat- bone structure, a favorable result compared to the maximum reported pulsed photothermal radiometric depth resolution < 1 mm in turbid biological media. Compared to radar peak delay and amplitude, the long-delayed radar output amplitude is found to be more sensitive to subsurface conditions. Two-dimensional spatial plots of this parameter depicting the back surface conditions of bones with and without fat-tissue overlayers are presented.

  3. Muscle, tendons, and bone: structural changes during denervation and FES treatment.

    PubMed

    Gargiulo, Paolo; Reynisson, Páll Jens; Helgason, Benedikt; Kern, Helmut; Mayr, Winfried; Ingvarsson, Páll; Helgason, Thordur; Carraro, Ugo

    2011-09-01

    This paper describes a novel approach to determine structural changes in bone, muscle, and tendons using medical imaging, finite element models, and processing techniques to evaluate and quantify: (1) progression of atrophy in permanently lower motor neuron (LMN) denervated human muscles, and tendons; (2) their recovery as induced by functional electrical stimulation (FES); and (3) changes in bone mineral density and bone strength as effect of FES treatment. Briefly, we used three-dimensional reconstruction of muscle belly, tendons, and bone images to study the structural changes occurring in these tissues in paralysed subjects after complete lumbar-ischiadic spinal cord injury (SCI). These subjects were recruited through the European project RISE, an endeavour designed to establish a novel clinical rehabilitation method for patients who have permanent and non-recoverable muscle LMN denervation in the lower extremities. This paper describes the use of segmentation techniques to study muscles, tendons, and bone in several states: healthy, LMN denervated-degenerated but not stimulated, and LMN denervated-stimulated. Here, we have used medical images to develop three-dimensional models and advanced imaging, including computational tools to display tissue density. Different tissues are visualized associating proper Hounsfield intervals defined experimentally to fat, connective tissue, and muscle. Finite element techniques are used to calculate Young's modulus on the patella bone and to analyse correlation between muscle contraction and bone strength changes. These analyses show restoration of muscular structures, tendons, and bone after FES as well as decline of the same tissues when treatment is not performed. This study suggests also a correlation between muscle growth due to FES treatment and increase in density and strength in patella bone. Segmentation techniques and finite element analysis allow the study of the structural changes of human skeletal muscle

  4. Human collagen-based multilayer scaffolds for tendon-to-bone interface tissue engineering.

    PubMed

    Kim, Beob Soo; Kim, Eun Ji; Choi, Ji Suk; Jeong, Ji Hoon; Jo, Chris Hyunchul; Cho, Yong Woo

    2014-11-01

    The natural tendon-to-bone region has a gradient in structure and composition, which is translated into a spatial variation of chemical, physical, and biological properties. This unique transitional tissue between bone and tendon is not normally recreated during natural bone-to-tendon healing. In this study, we have developed a human collagen-based multilayer scaffold mimicking the tendon-to-bone region. The scaffold consists of four different layers with the following composition gradient: (a) a tendon layer composed of collagen; (b) an uncalcified fibrocartilage layer composed of collagen and chondroitin sulfate; (c) a calcified fibrocartilage layer composed of collagen and less apatite; (d) a bone layer composed of collagen and apatite. The chemical, physical, and mechanical properties of the scaffold were characterized by a scanning electron microscope, porosimeter, universal tensile machine, Fourier transform infrared spectrometer, energy dispersive X-ray analysis apparatus, and thermogravimetric analysis apparatus. The multilayer scaffold provided a gradual transition of the physical, chemical, and mechanical environment and supported the adhesion and proliferation of human fibroblasts, chondrocytes, and osteoblasts toward each corresponding matrix. Overall, our results suggest the feasibility of a human collagen-based multilayer scaffold for regeneration of hard-to-soft interface tissues. © 2014 Wiley Periodicals, Inc.

  5. The state of human bone tissue during space flight.

    PubMed

    Oganov, V S; Rakhmanov, A S; Novikov, V E; Zatsepin, S T; Rodionova, S S; Cann, C

    1991-01-01

    The results of studying the bone tissue of cosmonauts after the flights (4-8 month) have been compared to the data of investigating the healthy individuals during head-down tilt (HDT, 370 days). Noninvasive methods (computer tomography, gammaphoton absorptiometry) revealed a decrease in the vertebral spongy mineral density or a increase of this parameter by a similar magnitude versus the individual preflight values in some cosmonauts. During studies of clinical cases of osteoporosis it was shown that the vertebral mineral density ratios and presence or absence of vertebral compression fractures in different age groups are nonequal.

  6. The state of human bone tissue during space flight

    NASA Astrophysics Data System (ADS)

    Oganov, V. S.; Rakhmanov, A. S.; Novikov, V. E.; Zatsepin, S. T.; Rodionova, S. S.; Cann, Ch.

    The results of studying the bone tissue of cosmonauts after the flights (4-8 month) have been compared to the data of investigating the healthy individuals during head-down tilt (HDT, 370 days). Noninvasive methods (computer tomography, gammaphoton absorptiometry) revealed a decrease in the vertebral spongy mineral density or a increase of this parameter by a similar magnitude versus the individual preflight values in some cosmonauts. During studies of clinical cases of osteoporosis it was shown that the vertebral mineral density ratios and presence or absence of vertebral compression fractures in different age groups are nonequal.

  7. Highly structured and surface modified poly(epsilon-caprolactone) scaffolds derived from co-continuous polymer blends for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Mehr, Nima Ghavidel

    L) surface modification has never been evaluated before. This part of the study tests the hypothesis that in vitro osteogenesis can be achieved in 3D PCL scaffolds with fully interconnected pores of 84 im or 141 im average diameter and biomineralization can be enhanced when pore surfaces are coated with chitosan adsorbed to LbL deposited polyelectrolytes. In order to reduce the errors originating from cell infiltration inefficiencies, the most competent cell seeding protocol has to be defined. Among classical cell seeding at 37°C, 2-step seeding at 37°C and cold seeding at 4°C in a medium containing 2% FBS, the last strategy proved to yield the best population of freshly trypsinized hBMSCs at all depths of the 1mm-thick scaffolds. hBMSCs cold-seeded in PCL scaffolds with or without an LbL-chitosan coating were cultured for 10 days in proliferation medium, followed by 21 days in osteogenic medium. At day 2, MSCs formed sparse monolayers with rounded cell morphologies with thin filopodia anchored to the unmodified PCL, as compared to more spread cells on chitosan-coated pore surfaces. At day 10, cells proliferated as an external layer, and migrated onto secreted collagen networks that filled the interpore spaces of all scaffolds, but only adhered to chitosan-coated pore surfaces. At day 31, similar levels of tissue formed in scaffolds with and without chitosan, but more tissue was deposited in the outer pores than the inner pores. Furthermore, more biomineralized matrix was observed in the inner 84 im chitosan-coated pores (p<0.05). In the PCL-only samples, haphazard mineral deposits were observed in highly colonized outer layers and in the inner 141 im pores. MSCs cultured on chitosan-coated 2D control surfaces show higher alkaline phosphatase staining but negligible mineralization. This study showed that hBMSCs survive, proliferate, and attach to fibrotic matrix rather than the PCL-only scaffold pore surfaces. LbL-chitosan-coated scaffolds showed more biomineralization in

  8. Soft tissues, areal bone mineral density and hip geometry estimates in active young boys: the PRO-BONE study.

    PubMed

    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.

  9. Scaffolds for Bone Tissue Engineering: State of the art and new perspectives.

    PubMed

    Roseti, Livia; Parisi, Valentina; Petretta, Mauro; Cavallo, Carola; Desando, Giovanna; Bartolotti, Isabella; Grigolo, Brunella

    2017-09-01

    This review is intended to give a state of the art description of scaffold-based strategies utilized in Bone Tissue Engineering. Numerous scaffolds have been tested in the orthopedic field with the aim of improving cell viability, attachment, proliferation and homing, osteogenic differentiation, vascularization, host integration and load bearing. The main traits that characterize a scaffold suitable for bone regeneration concerning its biological requirements, structural features, composition, and types of fabrication are described in detail. Attention is then focused on conventional and Rapid Prototyping scaffold manufacturing techniques. Conventional manufacturing approaches are subtractive methods where parts of the material are removed from an initial block to achieve the desired shape. Rapid Prototyping techniques, introduced to overcome standard techniques limitations, are additive fabrication processes that manufacture the final three-dimensional object via deposition of overlying layers. An important improvement is the possibility to create custom-made products by means of computer assisted technologies, starting from patient's medical images. As a conclusion, it is highlighted that, despite its encouraging results, the clinical approach of Bone Tissue Engineering has not taken place on a large scale yet, due to the need of more in depth studies, its high manufacturing costs and the difficulty to obtain regulatory approval. PUBMED search terms utilized to write this review were: "Bone Tissue Engineering", "regenerative medicine", "bioactive scaffolds", "biomimetic scaffolds", "3D printing", "3D bioprinting", "vascularization" and "dentistry". Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Tautomerizable β-ketonitrile copolymers for bone tissue engineering: Studies of biocompatibility and cytotoxicity.

    PubMed

    Lastra, M Laura; Molinuevo, M Silvina; Giussi, Juan M; Allegretti, Patricia E; Blaszczyk-Lezak, Iwona; Mijangos, Carmen; Cortizo, M Susana

    2015-06-01

    β-Ketonitrile tautomeric copolymers have demonstrated tunable hydrophilicity/hydrophobicity properties according to surrounding environment, and mechanical properties similar to those of human bone tissue. Both characteristic properties make them promising candidates as biomaterials for bone tissue engineering. Based on this knowledge we have designed two scaffolds based on β-ketonitrile tautomeric copolymers which differ in chemical composition and surface morphology. Two of them were nanostructured, using an anodized aluminum oxide (AAO) template, and the other two obtained by solvent casting methodology. They were used to evaluate the effect of the composition and their structural modifications on the biocompatibility, cytotoxicity and degradation properties. Our results showed that the nanostructured scaffolds exhibited higher degradation rate by macrophages than casted scaffolds (6 and 2.5% of degradation for nanostructured and casted scaffolds, respectively), a degradation rate compatible with bone regeneration times. We also demonstrated that the β-ketonitrile tautomeric based scaffolds supported osteoblastic cell proliferation and differentiation without cytotoxic effects, suggesting that these biomaterials could be useful in the bone tissue engineering field. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue.

    PubMed

    Byambaa, Batzaya; Annabi, Nasim; Yue, Kan; Trujillo-de Santiago, Grissel; Alvarez, Mario Moisés; Jia, Weitao; Kazemzadeh-Narbat, Mehdi; Shin, Su Ryon; Tamayol, Ali; Khademhosseini, Ali

    2017-08-01

    Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMALOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Comparison of mechanical behavior between implant-simulated bone tissue and implant-jaw bone tissue interfaces based on Pull Out testing

    NASA Astrophysics Data System (ADS)

    Lopez, C.; Muñoz, J. C.; Pinillos, J. C.

    2013-11-01

    The main purpose of this research was to achieve a better understanding of the relationship within the mechanical properties of human cadaver jaw bone with kind D2 density regarding a substitute polymer to simulate bone tissue, proposed by the ASTM, to evaluate orthopedic implants. However, despite the existence of several densities of foams and his mechanical characterization has been classified into different degrees of tissue densities to simulate cancellous and cortical bone, the value of the densities are different contrasted with the densities of bone tissue, making difficult to establish direct relationship about mechanical behavior between the polymer and the bone material, and therefore no clear criteria known for choosing the polymeric foam which describes the mechanical behavior of tissue for a specific or particular study. To understand such behavior from bone tissue regarding the polymer samples, on this research was a dental implant inserted into the samples, and subjected to destructive Pull Out test according to ASTM F543The Pull Out strength was compared between implant-jawbone and implant-rigid polyurethane foam interfaces. Thus, the test pieces with mechanical behavior similar to bone tissue, enabling an approximation to choose degree appropriate of polymer to replace the bone tissue in future trials biomechanical.

  13. Informing phenomenological structural bone remodelling with a mechanistic poroelastic model.

    PubMed

    Villette, Claire C; Phillips, Andrew T M

    2016-02-01

    Studies suggest that fluid motion in the extracellular space may be involved in the cellular mechanosensitivity at play in the bone tissue adaptation process. Previously, the authors developed a mesoscale predictive structural model of the femur using truss elements to represent trabecular bone, relying on a phenomenological strain-based bone adaptation algorithm. In order to introduce a response to bending and shear, the authors considered the use of beam elements, requiring a new formulation of the bone adaptation drivers. The primary goal of the study presented here was to isolate phenomenological drivers based on the results of a mechanistic approach to be used with a beam element representation of trabecular bone in mesoscale structural modelling. A single-beam model and a microscale poroelastic model of a single trabecula were developed. A mechanistic iterative adaptation algorithm was implemented based on fluid motion velocity through the bone matrix pores to predict the remodelled geometries of the poroelastic trabecula under 42 different loading scenarios. Regression analyses were used to correlate the changes in poroelastic trabecula thickness and orientation to the initial strain outputs of the beam model. Linear (R(2) > 0.998) and third-order polynomial (R(2) > 0.98) relationships were found between change in cross section and axial strain at the central axis, and between beam reorientation and ratio of bending strain to axial strain, respectively. Implementing these relationships into the phenomenological predictive algorithm for the mesoscale structural femur has the potential to produce a model combining biofidelic structure and mechanical behaviour with computational efficiency.

  14. Fabrication of Bioceramic Bone Scaffolds for Tissue Engineering

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    Bourgeois, Damien; Burt-Pichat, Brigitte; Le Goff, Xavier; Garrevoet, Jan; Tack, Pieter; Falkenberg, Gerald; Van Hoorebeke, Luc; Vincze, Laszlo; Denecke, Melissa A; Meyer, Daniel; Vidaud, Claude; Boivin, Georges

    2015-09-01

    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.

  16. Osteoinductive small molecules: growth factor alternatives for bone tissue engineering.

    PubMed

    Aravamudhan, Aja; Ramos, Daisy M; Nip, Jonathan; Subramanian, Aditi; James, Roshan; Harmon, Matthew D; Yu, Xiaojun; Kumbar, Sangamesh G

    2013-01-01

    Tissue engineering aims to repair, restore, and regenerate lost or damaged tissues by using biomaterials, cells, mechanical forces and factors (chemical and biological) alone or in combination. Growth factors are routinely used in the tissue engineering approach to expedite the process of regeneration. The growth factor approach has been hampered by several complications including high dose requirements, lower half-life, protein instability, higher costs and undesired side effects. Recently a variety of alternative small molecules of both natural and synthetic origin have been explored as alternatives to growth factors for tissue regeneration applications. Small molecules are simple biochemical components that elicit certain cellular responses through signaling cascades. Small molecules present a viable alternative to biological factors. Small molecule strategies can reduce various side effects, maintain bioactivity in a biological environment and minimize cost issues associated with complex biological growth factors. This manuscript focuses on three-osteoinductive small molecules, namely melatonin, resveratrol (from natural sources) and purmorphamine (synthetically designed) as inducers of bone formation and osteogenic differentiation of stem cells. Efforts have been made to summarize possible biological pathways involved in the action of each of these drugs. Melatonin is known to affect Mitogen Activated Protein (MAP) kinase, Bone morphogenic protein (BMP) and canonical wnt signaling. Resveratrol is known to activate cascades involving Wnt and NAD-dependent deacetylase sirtuin-1 (Sirt1). Purmorphamine is a Hedgehog (Hh) pathway agonist as it acts on Smoothened (Smo) receptors. These mechanisms and the way they are affected by the respective small molecules will also be discussed in the manuscript.

  17. Engineering a mimicry of bone marrow tissue ex vivo.

    PubMed

    Panoskaltsis, Nicki; Mantalaris, Athanasios; Wu, J H David

    2005-07-01

    Hematopoietic stem cells reside in specific niches in the bone marrow and give rise to either more stem cells or maturing hematopoietic progeny depending on the signals provided in the bone marrow microenvironment. This microenvironment is comprised of cellular components as well as soluble constituents called cytokines. The use of cytokines alone for the ex vivo expansion of stem cells in flat, two-dimensional culture flasks, dishes or bags is inadequate and, given the three-dimensionality of the in vivo bone marrow microenvironment, inappropriate. Three-dimensional culture conditions can therefore provide an ex vivo mimicry of bone marrow, recapitulate the desired niche, and provide a suitable environment for stem cell expansion and differentiation. Choice of scaffold, manipulation and reproducibility of the scaffold properties and directed structuring of the niche, by choosing pore size and porosity may inform the resident stem cells of their fate in a directed fashion. The use of bioreactors for cultivation of hematopoietic cells will allow for culture control, optimization, standardization, scale-up, and a "hands-off" operation making the end-product dependable, predictable and free of contaminants, and therefore suitable for human use and therapeutic applications.

  18. Biomechanical comparison of the hand-based transplant used in bone-tissue-bone scapho-lunate ligament reconstruction.

    PubMed

    Gay, A M; Thoreson, A; Berger, R A

    2014-02-01

    Although work has been published comparing the five most commonly used transplant techniques to the properties of the scapho-lunate interosseous ligament (SLIL), no study has been carried out which compares the biomechanical properties of the different bone-tissue-bone autografts to each other, using a standard methodology of testing. The hypothesis of this study was that mechanically significant differences in the material properties of commonly used bone-tissue-bone exist when compared to each other. We tested the dorsal part of the SLIL and the five most quoted transplants in the literature: capitate to trapezoid; trapezoid to second metacarpal; third metacarpal-carpal; dorsal capitate-hamate; 4-5 extensor retinaculum. For each transplant, we measured failure load, failure displacement, width, and thickness. Anova was used to compare the different results obtained and the level of significance attributed to P<0.05. Load to failure were: SLIL 94.3±42.86N; capitate to trapezoid 37.7±23.13N; trapezoid to second metacarpal 45.43±14.28N; third metacarpal-carpal 60.11±19.94N; dorsal capitate-hamate 63±25.51N; 4-5 retinaculum 15.67±10.7N. Only the dorsal capitate-hamate ligament showed to have no significant (P>0.05) difference in term of load to failure, all the others was significantly weaker (P<0.05). Previous biomechanical studies have identified the dorsal region of the SLIL as the most structurally and functionally important area of the SLIL. As a result, attention has been more specifically brought to the replacement of the dorsal portion of the SLIL. An attempt to achieve a reconstruction that reproduces more closely the SLIL has generated research on the use of bone-tissue-bone composite graft, several donor sites have been used in order to find the most similar. Our results suggest that, using a normalized method to compare the previously described grafts harvested at the wrist level, that the dorsal capitate-hamate ligament has the closest properties

  19. Biological evaluation of porous aliphatic polyurethane/hydroxyapatite composite scaffolds for bone tissue engineering.

    PubMed

    Yang, Wanxun; Both, Sanne K; Zuo, Yi; Birgani, Zeinab Tahmasebi; Habibovic, Pamela; Li, Yubao; Jansen, John A; Yang, Fang

    2015-07-01

    Biomaterial scaffolds meant to function as supporting structures to osteogenic cells play a pivotal role in bone tissue engineering. Recently, we synthesized an aliphatic polyurethane (PU) scaffold via a foaming method using non-toxic components. Through this procedure a uniform interconnected porous structure was created. Furthermore, hydroxyapatite (HA) particles were introduced into this process to increase the bioactivity of the PU matrix. To evaluate the biological performances of these PU-based scaffolds, their influence on in vitro cellular behavior and in vivo bone forming capacity of the engineered cell-scaffold constructs was investigated in this study. A simulated body fluid test demonstrated that the incorporation of 40 wt % HA particles significantly promoted the biomineralization ability of the PU scaffolds. Enhanced in vitro proliferation and osteogenic differentiation of the seeded mesenchymal stem cells were also observed on the PU/HA composite. Next, the cell-scaffold constructs were implanted subcutaneously in a nude mice model. After 8 weeks, a considerable amount of vascularized bone tissue with initial marrow stroma development was generated in both PU and PU/HA40 scaffold. In conclusion, the PU/HA composite is a potential scaffold for bone regeneration applications.

  20. Preparation and mechanical property of a novel 3D porous magnesium scaffold for bone tissue engineering.

    PubMed

    Zhang, Xue; Li, Xiao-Wu; Li, Ji-Guang; Sun, Xu-Dong

    2014-09-01

    Porous magnesium has been recently recognized as a biodegradable metal for bone substitute applications. A novel porous Mg scaffold with three-dimensional (3D) interconnected pores and with a porosity of 33-54% was produced by the fiber deposition hot pressing (FDHP) technology. The microstructure and morphologies of the porous Mg scaffold were characterized by scanning electron microscopy (SEM), and the effects of porosities on the microstructure and mechanical properties of the porous Mg were investigated. Experimental results indicate that the measured Young's modulus and compressive strength of the Mg scaffold are ranged in 0.10-0.37 GPa, and 11.1-30.3 MPa, respectively, which are fairly comparable to those of cancellous bone. Such a porous Mg scaffold having a 3D interconnected network structure has the potential to be used in bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. In vitro evaluation of ionizing radiation effects in bone tissue by FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Zezell, Denise Maria; Veloso, Marcelo Noronha; Dias, Derly Augusto; Politano, Rodolfo; Benetti, Carolina

    2015-06-01

    We verified the changes promoted by ionizing radiation in bone tissue using FTIR. Samples of bovine bone were irradiated using Cobalt-60 with 0.01kGy, 0.1kGy, 1kGy, 15kGy and 75kGy. The effects of ionizing irradiation on chemical structure of bone, were studied considering the sub-bands of amide I, the crystallinity index and relation of organic and inorganic materials. ATR-FTIR spectroscopy showed changes in organic components and in hydroxyapatite crystals organization. High correlation with statistical significance was observed between (amideIII+collagen)/ ν1,ν3PO4, crystallinity and mechanical properties of the samples.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2010-01-01

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

  5. Collagen in Human Tissues: Structure, Function, and Biomedical Implications from a Tissue Engineering Perspective

    NASA Astrophysics Data System (ADS)

    Balasubramanian, Preethi; Prabhakaran, Molamma P.; Sireesha, Merum; Ramakrishna, Seeram

    The extracellular matrix is a complex biological structure encoded with various proteins, among which the collagen family is the most significant and abundant of all, contributing 30-35% of the whole-body protein. "Collagen" is a generic term for proteins that forms a triple-helical structure with three polypeptide chains, and around 29 types of collagen have been identified up to now. Although most of the members of the collagen family form such supramolecular structures, extensive diversity exists between each type of collagen. The diversity is not only based on the molecular assembly and supramolecular structures of collagen types but is also observed within its tissue distribution, function, and pathology. Collagens possess complex hierarchical structures and are present in various forms such as collagen fibrils (1.5-3.5 nm wide), collagen fibers (50-70 nm wide), and collagen bundles (150-250 nm wide), with distinct properties characteristic of each tissue providing elasticity to skin, softness of the cartilage, stiffness of the bone and tendon, transparency of the cornea, opaqueness of the sclera, etc. There exists an exclusive relation between the structural features of collagen in human tissues (such as the collagen composition, collagen fibril length and diameter, collagen distribution, and collagen fiber orientation) and its tissue-specific mechanical properties. In bone, a transverse collagen fiber orientation prevails in regions of higher compressive stress whereas longitudinally oriented collagen fibers correlate to higher tensile stress. The immense versatility of collagen compels a thorough understanding of the collagen types and this review discusses the major types of collagen found in different human tissues, highlighting their tissue-specific uniqueness based on their structure and mechanical function. The changes in collagen during a specific tissue damage or injury are discussed further, focusing on the many tissue engineering applications for

  6. Peculiarities of the bone tissue resorption under microgravity conditions

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

    Sibonga, J. D.; Iwaniec, U.; Wu, H.

    2011-01-01

    PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal

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

    NASA Astrophysics Data System (ADS)

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

    PubMed

    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.

  10. Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration.

    PubMed

    Ripamonti, Ugo; Petit, Jean-Claude

    2009-01-01

    'Bone: Formation by autoinduction', initiates by invocation of soluble molecular signals which, when combined to insoluble signals or substrata trigger the ripple-like cascade of bone differentiation by induction. The osteogenic proteins of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs), and uniquely in the non-human primate Papio ursinus also the three mammalian TGF-beta isoforms, induce endochondral bone formation as recapitulation of embryonic development. The pleiotropic activities of the BMPs/OPs are vast and include the induction of periodontal tissue regeneration. Implantation of naturally derived highly purified osteogenic fractions after sequential adsorption/affinity and gel filtration chromatography in mandibular Class II furcation defects of P. ursinus induces cementogenesis as highly cellular collagenic cementoid attached to the exposed dentine with foci of nascent mineralization with inserted de novo generated Sharpey's fibres. Recombinant human osteogenic protein-1 (hOP-1) when implanted in Class II furcation defects of P. ursinus with surgically exposed dentine matrix preferentially initiates the induction of cementogenesis; on the other hand, hBMP-2 preferentially induces alveolar bone regeneration with mineralized bone covered by prominent osteoid seams. Long-term studies with gamma-irradiated 0.5 and 2.5mg hOP-1 per gram of xenogeneic bovine collagenous matrix induce the restitutio ad integrum of the periodontal tissues in furcation defects exposed by chronic periodontitis in P. ursinus. A challenging question for tissue engineering and regenerative medicine is whether the presence of molecularly different osteogenic proteins of the TGF-beta superfamily has a therapeutic significance. Mechanistically, the specificity of hOP-1 primarily initiating cementogenesis in periodontal defects is regulated by both the dentine extracellular matrix upon which responding cells attach and

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

    PubMed Central

    Wu, Chengtie; Chang, Jiang

    2012-01-01

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

  12. In-vitro imaging of bone tissue and monitoring of tissue viability by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Wang, Ruikang K.; El Haj, Alicia

    2001-07-01

    Optical coherence tomography (OCT) has developed as a promising medical diagnostic imaging technology for non- invasive in situ cross-sectional imaging of biological tissues. We present this technique to image bone tissue and to monitor the redox state of mitochondria enzyme Cytochrome oxidase (CytOx) in bone for applications in tissue engineering. Superluminescent diode (SLD) with its peak emission wavelength (λ = 820nm) on the absorption band of oxidized form of CytOx was used in the experiments. The results demonstrate that the OCT system is capable of imaging the calvaria of newborn rats tomographically with a resolution at 9 microns, which could only be previously obtained by the conventional excisional biopsy. The thickness of periosteum of various calvarias from different ages of rats can be accurately determined by the system. The backscattered power-versus-depth profile form the liquid phantoms (naphthol green B with intralipid) and tissue specimens (periosteum of calvaria from newborn rats) are used to quantify the absorption changes of the sample. Absorption coefficients of naphthol green B could be quantified accurately by the linear relationship between attenuation coefficients from the slopes of the reflected signals and naphthol green B concentration. The results also show that the attenuation coefficient decreases in periosteums as CytOx being reduced by sodium dithionite, demonstrating the feasibility of this method to monitor the redox state of tissues studied.

  13. Bone marrow adipose tissue as an endocrine organ: close to the bone?

    PubMed

    Sulston, Richard J; Cawthorn, William P

    2016-10-01

    White adipose tissue (WAT) is a major endocrine organ, secreting a diverse range of hormones, lipid species, cytokines and other factors to exert diverse local and systemic effects. These secreted products, known as 'adipokines', contribute extensively to WAT's impact on physiology and disease. Adipocytes also exist in the bone marrow (BM), but unlike WAT, study of this bone marrow adipose tissue (MAT) has been relatively limited. We recently discovered that MAT contributes to circulating adiponectin, an adipokine that mediates cardiometabolic benefits. Moreover, we found that MAT expansion exerts systemic effects. Together, these observations identify MAT as an endocrine organ. Additional studies are revealing further secretory functions of MAT, including production of other adipokines, cytokines and lipids that exert local effects within bone. These observations suggest that, like WAT, MAT has secretory functions with diverse potential effects, both locally and systemically. A major limitation is that these findings are often based on in vitro approaches that may not faithfully recapitulate the characteristics and functions of BM adipocytes in vivo. This underscores the need to develop improved methods for in vivo analysis of MAT function, including more robust transgenic models for MAT targeting, and continued development of techniques for non-invasive analysis of MAT quantity and quality in humans. Although many aspects of MAT formation and function remain poorly understood, MAT is now attracting increasing research focus; hence, there is much promise for further advances in our understanding of MAT as an endocrine organ, and how MAT impacts human health and disease.

  14. A polycaprolactone/cuttlefish bone-derived hydroxyapatite composite porous scaffold for bone tissue engineering.

    PubMed

    Kim, Beom-Su; Yang, Sun-Sik; Lee, Jun

    2014-07-01

    Cuttlefish bone (CB) is an attractive natural biomaterial source to obtain hydroxyapatite (HAp). In this study, a porous polycaprolactone (PCL) scaffold incorporating CB-derived HAp (CB-HAp) powder was fabricated using the solvent casting and particulate leaching method. The presence of CB-HAp in PCL/CB-HAp scaffold was confirmed by X-ray diffraction (XRD). Scanning electron microscopy (SEM) and porosity analysis showed that the average pore dimension of the fabricated scaffold was approximately 200-300 μm, with ∼85% porosity, and that the compressive modulus increased after addition of CB-HAp powders. In vitro tests such as cell proliferation assay, cytotoxicity analysis, cell attachment observations, and alkaline phosphatase activity assays showed that the PCL/CB-HAp scaffold could improve the proliferation, viability, adherence, and osteoblast differentiation rate of MG-63 cells. When surgically implanted into rabbit calvarial bone defects, consistent with the in vitro results, PCL/CB-HAp scaffold implantation resulted in significantly higher new bone formation than did implantation of PCL alone. These findings suggest that addition of CB-HAp powder to the PCL scaffold can improve cellular response and that the PCL/CB-HAp composite scaffold has great potential for use in bone tissue engineering. © 2013 Wiley Periodicals, Inc.

  15. [RESEARCH PROGRESS OF THREE-DIMENSIONAL PRINTING POROUS SCAFFOLDS FOR BONE TISSUE ENGINEERING].

    PubMed

    Wu, Tianqi; Yang, Chunxi

    2016-04-01

    To summarize the research progress of several three-dimensional (3-D)-printing scaffold materials in bone tissue engineering. The recent domestic and international articles about 3-D printing scaffold materials were reviewed and summarized. Compared with conventional manufacturing methods, 3-D printing has distinctive advantages, such as enhancing the controllability of the structure and increasing the productivity. In addition to the traditional metal and ceramic scaffolds, 3-D printing scaffolds carrying seeding cells and tissue factors as well as scaffolds filling particular drugs for special need have been paid more and more attention. The development of 3-D printing porous scaffolds have revealed new perspectives in bone repairing. But it is still at the initial stage, more basic and clinical researches are still needed.

  16. Chitosan scaffolds containing silicon dioxide and zirconia nano particles for bone tissue engineering.

    PubMed

    Pattnaik, Soumitri; Nethala, Sricharan; Tripathi, Anjali; Saravanan, Sekaran; Moorthi, Ambigapathi; Selvamurugan, Nagarajan

    2011-12-01

    A scaffold harboring the desired features such as biodegradation, biocompatibility, porous structure could serve as template for bone tissue engineering. In the present study, chitosan (CS), nano-scaled silicon dioxide (Si) and zirconia (Zr) were combined by freeze drying technique to fabricate a bio-composite scaffold. The bio-composite scaffold (CS/Si/Zr) was characterized by SEM, XRD and FT-IR studies. The scaffold possessed a porous nature with pore dimensions suitable for cell infiltration and colonization. The presence of zirconia in the CS/Si/Zr scaffold decreased swelling and increased biodegradation, protein adsorption and bio-mineralization properties. The CS/Si/Zr scaffold was also found to be non-toxic to rat osteoprogenitor cells. Thus, we suggest that CS/Si/Zr bio-composite scaffold is a potential candidate to be used for bone tissue engineering. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Biotemplated syntheses of macroporous materials for bone tissue engineering scaffolds and experiments in vitro and vivo.

    PubMed

    Li, Xing; Zhao, Yayun; Bing, Yue; Li, Yaping; Gan, Ning; Guo, Zhiyong; Peng, Zhaoxiang; Zhu, Yabin

    2013-06-26

    The macroporous materials were prepared from the transformation of cuttlebone as biotemplates under hydrothermal reactions and characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric/differential thermal analyses (TG-DTA), and scanning electron microscopy (SEM). Cell experimental results showed that the prepared materials as bone tissue engineering scaffolds or fillers had fine biocompatibility suitable for adhesion and proliferation of the hMSCs (human marrow mesenchymal stem cells). Histological analyses were carried out by implanting the scaffolds into a rabbit femur, where the bioresorption, degradation, and biological activity of the scaffolds were observed in the animal body. The prepared scaffolds kept the original three-dimensional frameworks with the ordered porous structures, which made for blood circulation, nutrition supply, and the cells implantation. The biotemplated syntheses could provide a new effective approach to prepare the bone tissue engineering scaffold materials.

  18. Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering.

    PubMed

    Long, Teng; Yang, Jun; Shi, Shan-Shan; Guo, Ya-Ping; Ke, Qin-Fei; Zhu, Zhen-An

    2015-10-01

    An ideal scaffold for bone tissue engineering should have interconnected porous structure, good biocompatibility, and mechanical properties well-matched with natural bones. Collagen is the key component in the extracellular matrix (ECM) of natural bones, and plays an important role in bone regeneration. The biological activity of collagen has promoted it to be an advantageous biomaterial for bone tissue engineering; however, the mechanical properties of these scaffolds are insufficient and the porous structures are not stable in the wet state. An effective strategy to solve this problem is to fabricate a hybrid scaffold of biologically derived and synthetic material, which have the necessary bioactivity and mechanical stability needed for bone synthesis. In this work, a three-dimensional macroporous bone scaffold based on collagen (CO) fiber and bioglass (BG) is fabricated by a slurry-dipping technique, and its relevant mechanical and biological properties are evaluated. The CO/BG scaffold is interconnected with a porosity of 81 ± 4.6% and pore size of 40-200 μm. Compared with CO scaffold, water absorption value of CO/BG scaffold decreases greatly from 889% to 52%, which significantly alleviates the swelling behavior of collagen and improves the stability of scaffold structure. The CO/BG scaffold has a compression strength of 5.8 ± 1.6 MPa and an elastic modulus of 0.35 ± 0.01 Gpa, which are well-matched with the mechanical properties of trabecular bones. In vitro cell assays demonstrate that the CO/BG scaffold has good biocompatibility to facilitate the spreading and proliferation of human bone marrow stromal cells. Hence, the CO/BG scaffold is promising for bone tissue engineering application.

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

    NASA Astrophysics Data System (ADS)

    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

  20. Unusual intraosseous fossilized soft tissues from the Middle Triassic Nothosaurus bone

    NASA Astrophysics Data System (ADS)

    Surmik, Dawid; Rothschild, Bruce M.; Pawlicki, Roman

    2017-04-01

    Fossilized soft tissues, occasionally found together with skeletal remains, provide insights to the physiology and functional morphology of extinct organisms. Herein, we present unusual fossilized structures from the cortical region of bone identified in isolated skeletal remains of Middle Triassic nothosaurs from Upper Silesia, Poland. The ribbed or annuli-shaped structures have been found in a sample of partially demineralized coracoid and are interpreted as either giant red blood cells or as blood vessel walls. The most probable function is reinforcing the blood vessels from changes of nitrogen pressure in air-breathing diving reptiles. These structures seem to have been built of extensible muscle layers which prevent the vessel damage during rapid ascent. Such suspected function presented here is parsimonious with results of previous studies, which indicate rarity of the pathological modification of bones associated with decompression syndrome in Middle Triassic nothosaurs.

  1. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

    PubMed

    Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

    2015-08-01

    Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Influence of structural load-bearing scaffolds on mechanical load- and BMP-2-mediated bone regeneration.

    PubMed

    McDermott, Anna M; Mason, Devon E; Lin, Angela S P; Guldberg, Robert E; Boerckel, Joel D

    2016-09-01

    A common design constraint in functional tissue engineering is that scaffolds intended for use in load-bearing sites possess similar mechanical properties to the replaced tissue. Here, we tested the hypothesis that in vivo loading would enhance bone morphogenetic protein-2 (BMP-2)-mediated bone regeneration in the presence of a load-bearing PLDL scaffold, whose pores and central core were filled with BMP-2-releasing alginate hydrogel. First, we evaluated the effects of in vivo mechanical loading on bone regeneration in the structural scaffolds. Second, we compared scaffold-mediated bone regeneration, independent of mechanical loading, with alginate hydrogel constructs, without the structural scaffold, that have been shown previously to facilitate in vivo mechanical stimulation of bone formation. Contrary to our hypothesis, mechanical loading had no effect on bone formation, distribution, or biomechanical properties in structural scaffolds. Independent of loading, the structural scaffolds reduced bone formation compared to non-structural alginate, particularly in regions in which the scaffold was concentrated, resulting in impaired functional regeneration. This is attributable to a combination of stress shielding by the scaffold and inhibition of cellular infiltration and tissue ingrowth. Collectively, these data question the necessity of scaffold similarity to mature tissue at the time of implantation and emphasize development of an environment conducive to cellular activation of matrix production and ultimate functional regeneration.

  3. Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

    PubMed Central

    Walker, John A.; Singleton, Brian M.; Hernandez, Jesus W.; Son, Jun-Sik; Kim, Su-Gwan; Oh, Daniel S.; Appleford, Mark R.; Ong, Joo L.; Wenke, Joseph C.

    2013-01-01

    a collagen membrane with a hydroxyapatite structural graft provides benefits for bone tissue regeneration in terms of early interfacial integration. PMID:22844877

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

    PubMed

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

    2014-04-01

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

  5. Current Concepts of Bone Tissue Engineering for Craniofacial Bone Defect Repair

    PubMed Central

    Fishero, Brian Alan; Kohli, Nikita; Das, Anusuya; Christophel, John Jared; Cui, Quanjun

    2014-01-01

    Craniofacial fractures and bony defects are common causes of morbidity and contribute to increasing health care costs. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. Current methods of repair and reconstruction include rigid fixation, grafting, and free tissue transfer. However, these methods carry innate complications, including plate extrusion, nonunion, graft/flap failure, and donor site morbidity. Recent research efforts have focused on using stem cells and synthetic scaffolds to heal critical-sized bone defects similar to those sustained from traumatic injury or ablative oncologic surgery. Growth factors can be used to augment both osteogenesis and neovascularization across these defects. Many different growth factor delivery techniques and scaffold compositions have been explored yet none have emerged as the universally accepted standard. In this review, we will discuss the recent literature regarding the use of stem cells, growth factors, and synthetic scaffolds as alternative methods of craniofacial fracture repair. PMID:25709750

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Developing bioactive composite scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Chen, Yun

    bone-like apatite/collagen composite coating. Saos-2 osteoblast-like cells were used to evaluate the cellular behaviors on these biomimetic coatings. Cell morphologies on the surfaces of PLLA films and scaffolds, PLLA films and scaffolds with apatite coating, and PLLA films and scaffolds with apatite/collagen composite coating were studied by SEM. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide (MTT) assay. In addition, differentiated cell function was assessed by measuring alkaline phosphatase activity. These results suggested that the apatite coating and apatite/collagen composite coating fabricated through the accelerated biomimetic processes could improve the interactions between osteoblasts and PLLA. The composite coating was more effective than apatite coating in improving such interactions. PLLA scaffolds coated with submicron collagen fibrils and submicron apatite paticulates are expected to be one of the promising 3D substrates for bone tissue engineering. To facilitate coating into scaffolds, the flowing condition was introduced into the accelerated biomimetic process. The apatite formed in the different sites in the scaffold was characterized using SEM. It was found that the accelerated biomimetic process performed in the flowing condition yielded more uniform spatial distribution of apatite particles than that in the regular shaking condition. This work provides a novel condition for obtaining uniform spatial distribution of bone-like apatite within the scaffolds in a timely manner, which is expected to facilitate uniform distribution of attached cells within the scaffoldsin vitro and in vivo.

  8. Utilizing core-shell fibrous collagen-alginate hydrogel cell delivery system for bone tissue engineering.

    PubMed

    Perez, Roman A; Kim, Meeju; Kim, Tae-Hyun; Kim, Joong-Hyun; Lee, Jae Ho; Park, Jeong-Hui; Knowles, Jonathan C; Kim, Hae-Won

    2014-01-01

    Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core-shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of ~700-1000 μm for the core and 200-500 μm for the shell area, which was largely dependent on the alginate concentration (2%-5%) as well as the injection rate (20-80 mL/h). The water uptake capacity of the core-shell carriers was as high as 98%, which could act as a pore channel to supply nutrients and oxygen to the cells. Degradation of the scaffolds showed a weight loss of ~22% at 7 days and ~43% at 14 days, suggesting a possible role as a degradable tissue-engineered construct. The MSCs encapsulated within the collagen core showed excellent viability, exhibiting significant cellular proliferation up to 21 days with levels comparable to those observed in the pure collagen gel matrix used as a control. A live/dead cell assay also confirmed similar percentages of live cells within the core-shell carrier compared to those in the pure collagen gel, suggesting the carrier was cell compatible and was effective for maintaining a cell population. Cells allowed to differentiate under osteogenic conditions expressed high levels of bone-related genes, including osteocalcin, bone sialoprotein, and osteopontin. Further, when the core-shell fibrous carriers were implanted in a rat calvarium defect, the bone healing was significantly

  9. Utilizing Core–Shell Fibrous Collagen-Alginate Hydrogel Cell Delivery System for Bone Tissue Engineering

    PubMed Central

    Perez, Roman A.; Kim, Meeju; Kim, Tae-Hyun; Kim, Joong-Hyun; Lee, Jae Ho; Park, Jeong-Hui; Knowles, Jonathan C.

    2014-01-01

    Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core–shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of ∼700–1000 μm for the core and 200–500 μm for the shell area, which was largely dependent on the alginate concentration (2%–5%) as well as the injection rate (20–80 mL/h). The water uptake capacity of the core–shell carriers was as high as 98%, which could act as a pore channel to supply nutrients and oxygen to the cells. Degradation of the scaffolds showed a weight loss of ∼22% at 7 days and ∼43% at 14 days, suggesting a possible role as a degradable tissue-engineered construct. The MSCs encapsulated within the collagen core showed excellent viability, exhibiting significant cellular proliferation up to 21 days with levels comparable to those observed in the pure collagen gel matrix used as a control. A live/dead cell assay also confirmed similar percentages of live cells within the core–shell carrier compared to those in the pure collagen gel, suggesting the carrier was cell compatible and was effective for maintaining a cell population. Cells allowed to differentiate under osteogenic conditions expressed high levels of bone-related genes, including osteocalcin, bone sialoprotein, and osteopontin. Further, when the core–shell fibrous carriers were implanted in a rat calvarium defect, the bone

  10. Longitudinal elastic properties and porosity of cortical bone tissue vary with age in human proximal femur.

    PubMed

    Malo, M K H; Rohrbach, D; Isaksson, H; Töyräs, J; Jurvelin, J S; Tamminen, I S; Kröger, H; Raum, K

    2013-04-01

    Tissue level structural and mechanical properties are important determinants of bone strength. As an individual ages, microstructural changes occur in bone, e.g., trabeculae and cortex become thinner and porosity increases. However, it is not known how the elastic properties of bone change during aging. Bone tissue may lose its elasticity and become more brittle and prone to fractures as it ages. In the present study the age-dependent variation in the spatial distributions of microstructural and microelastic properties of the human femoral neck and shaft were evaluated by using acoustic microscopy. Although these properties may not be directly measured in vivo, there is a major interest to investigate their relationships with the linear elastic measurements obtained by diagnostic ultrasound at the most severe fracture sites, e.g., the femoral neck. However, before the validity of novel in vivo techniques can be established, it is essential to understand the age-dependent variation in tissue elastic properties and porosity at different skeletal sites. A total of 42 transverse cross-sectional bone samples were obtained from the femoral neck (Fn) and proximal femoral shaft (Ps) of 21 men (mean±SD age 47.1±17.8, range 17-82years). Samples were quantitatively imaged using a scanning acoustic microscope (SAM) equipped with a 50MHz ultrasound transducer. Distributions of the elastic coefficient (c33) of cortical (Ct) and trabecular (Tr) tissues and microstructure of cortex (cortical thickness Ct.Th and porosity Ct.Po) were determined. Variations in c33 were observed with respect to tissue type (c33Trc33(Ct.Fn)=35.3GPa>c33(Tr.Ps)=33.8GPa>c33(Tr.Fn)=31.9GPa), and cadaver age (R(2)=0.28-0.46, p<0.05). Regional variations in porosity were found in the neck (superior 13.1%; inferior 6.1%; anterior 10.1%; posterior 8.6%) and in the shaft (medial 9.5%; lateral 7.7%; anterior 8.6%; posterior 12.0%). In conclusion, significant variations in

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

    PubMed Central

    Sun, Han; Yang, Hui-Lin

    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. PMID:25881610

  12. Bio-inspired mineralization of hydroxyapatite in 3D silk fibroin hydrogel for bone tissue engineering.

    PubMed

    Jin, Yashi; Kundu, Banani; Cai, Yurong; Kundu, Subhas C; Yao, Juming

    2015-10-01

    To fabricate hard tissue implants with bone-like structure using a biomimetic mineralization method is drawing much more attentions in bone tissue engineering. The present work focuses in designing 3D silk fibroin hydrogel to modulate the nucleation and growth of hydroxyapatite crystals via a simple ion diffusion method. The study indicates that Ca(2+) incorporation within the hydrogel provides the nucleation sites for hydroxyapatite crystals and subsequently regulates their oriented growth. The mineralization process is regulated in a Ca(2+) concentration- and minerlization time-dependent way. Further, the compressive strength of the mineralized hydrogels is directly proportional with the mineral content in hydrogel. The orchestrated organic/inorganic composite supports well the viability and proliferation of human osteoblast cells; improved cyto-compatibility with increased mineral content. Together, the present investigation reports a simple and biomimetic process to fabricate 3D bone-like biomaterial with desired efficacy to repair bone defects. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Ribose mediated crosslinking of collagen-hydroxyapatite hybrid scaffolds for bone tissue regeneration using biomimetic strategies.

    PubMed

    Krishnakumar, Gopal Shankar; Gostynska, Natalia; Campodoni, Elisabetta; Dapporto, Massimiliano; Montesi, Monica; Panseri, Silvia; Tampieri, Anna; Kon, Elizaveta; Marcacci, Maurilio; Sprio, Simone; Sandri, Monica

    2017-08-01

    This study explores for the first time the application of ribose as a highly biocompatible agent for the crosslinking of hybrid mineralized constructs, obtained by bio-inspired mineralization of self-assembling Type I collagen matrix with magnesium-doped-hydroxyapatite nanophase, towards a biomimetic mineralized 3D scaffolds (MgHA/Coll) with excellent compositional and structural mimicry of bone tissue. To this aim, two different crosslinking mechanisms in terms of pre-ribose glycation (before freeze drying) and post-ribose glycation (after freeze drying) were investigated. The obtained results explicate that with controlled freeze-drying, highly anisotropic porous structures with opportune macro-micro porosity are obtained. The physical-chemical features of the scaffolds characterized by XRD, FTIR, ICP and TGA demonstrated structural mimicry analogous to the native bone. The influence of ribose greatly assisted in decreasing solubility and increased enzymatic resistivity of the scaffolds. In addition, enhanced mechanical behaviour in response to compressive forces was achieved. Preliminary cell culture experiments reported good cytocompatibility with extensive cell adhesion, proliferation and colonization. Overall, scaffolds developed by pre-ribose glycation process are preferred, as the related crosslinking technique is more facile and robust to obtain functional scaffolds. As a proof of concept, we have demonstrated that ribose crosslinking is cost-effective, safe and functionally effective. This study also offers new insights and opportunities in developing promising scaffolds for bone tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Poly (glycerol sebacate) Elastomer Supports Bone Regeneration by Its Mechanical Properties Being Closer to Osteoid Tissue Rather than to Mature Bone.

    PubMed

    Zaky, S H; Lee, K W; Gao, J; Jensen, A; Verdelis, K; Wang, Y; Almarza, A J; Sfeir, C

    2017-01-18

    Mechanical load influences bone structure and mass. Arguing the importance of load-transduction, we investigated the mechanisms inducing bone formation using an elastomeric substrate. We characterized Poly (glycerol sebacate) (PGS) in-vitro for its mechanical properties, compatibility with osteoprogenitor cells regarding adhesion, proliferation, differentiation under compression versus static cultures and in-vivo for the regeneration of a rabbit ulna critical size defect. The load-transducing properties of PGS were compared in-vitro to a stiffer poly lactic-co- glycolic-acid (PLA/PGA) scaffold of similar porosity and interconnectivity. Under cyclic compression for 7days, we report focal adhesion kinase overexpression on the less stiff PGS and upregulation of the transcription factor Runx2 and late osteogenic markers osteocalcin and bone sialoprotein (1.7, 4.0 and 10.0 folds increase respectively). Upon implanting PGS in the rabbit ulna defect, histology and micro-computed tomography analysis showed complete gap bridging with new bone by the PGS elastomer by 8 weeks while minimal bone formation was seen in empty controls. Immunohistochemical analysis demonstrated the new bone to be primarily regenerated by recruited osteoprogenitors cells expressing periostin protein during early phase of maturation similar to physiological endochondral bone development. This study confirms PGS to be osteoconductive contributing to bone regeneration by recruiting host progenitor/stem cell populations and as a load-transducing substrate, transmits mechanical signals to the populated cells promoting differentiation and matrix maturation toward proper bone remodeling. We hence conclude that the material properties of PGS being closer to osteoid tissue rather than to mineralized bone, allows bone maturation on a substrate mechanically closer to where osteoprogenitor/stem cells differentiate to develop mature load-bearing bone.

  15. [New methods for the evaluation of bone quality. Assessment of bone structural property using imaging.

    PubMed

    Ito, Masako

    Structural property of bone includes micro- or nano-structural property of the trabecular and cortical bone, and macroscopic geometry. Radiological technique is useful to analyze the bone structural property;multi-detector row CT(MDCT)or high-resolution peripheral QCT(HR-pQCT)is available to analyze human bone in vivo. For the analysis of hip geometry, CT-based hip structure analysis(HSA)is available as well as DXA-based HSA. These structural parameters are related to biomechanical property, and these assessment tools provide information of pathological changes or the effects of anti-osteoporotic agents on bone.

  16. Fabrication of 3D porous SF/β-TCP hybrid scaffolds for bone tissue reconstruction.

    PubMed

    Park, Hyun Jung; Min, Kyung Dan; Lee, Min Chae; Kim, Soo Hyeon; Lee, Ok Joo; Ju, Hyung Woo; Moon, Bo Mi; Lee, Jung Min; Park, Ye Ri; Kim, Dong Wook; Jeong, Ju Yeon; Park, Chan Hum

    2016-07-01

    Bio-ceramic is a biomaterial actively studied in the field of bone tissue engineering. But, only certain ceramic materials can resolve the corrosion problem and possess the biological affinity of conventional metal biomaterials. Therefore, the recent development of composites of hybrid composites and polymers has been widely studied. In this study, we aimed to select the best scaffold of silk fibroin and β-TCP hybrid for bone tissue engineering. We fabricated three groups of scaffold such as SF (silk fibroin scaffold), GS (silk fibroin/small granule size of β-TCP scaffold) and GM (silk fibroin/medium granule size of β-TCP scaffold), and we compared the characteristics of each group. During characterization of the scaffold, we used scanning electron microscopy (SEM) and a Fourier transform infrared spectroscopy (FTIR) for structural analysis. We compared the physiological properties of the scaffold regarding the swelling ratio, water uptake and porosity. To evaluate the mechanical properties, we examined the compressive strength of the scaffold. During in vitro testing, we evaluated cell attachment and cell proliferation (CCK-8). Finally, we confirmed in vivo new bone regeneration from the implanted scaffolds using histological staining and micro-CT. From these evaluations, the fabricated scaffold demonstrated high porosity with good inter-pore connectivity, showed good biocompatibility and high compressive strength and modulus. In particular, the present study indicates that the GM scaffold using β-TCP accelerates new bone regeneration of implanted scaffolds. Accordingly, our scaffold is expected to act a useful application in the field of bone tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1779-1787, 2016.

  17. Micro-Brillouin scattering measurements in mature and newly formed bone tissue surrounding an implant.

    PubMed

    Mathieu, Vincent; Fukui, Kenji; Matsukawa, Mami; Kawabe, Masahiko; Vayron, Romain; Soffer, Emmanuel; Anagnostou, Fani; Haiat, Guillaume

    2011-02-01

    The evolution of implant stability in bone tissue remains difficult to assess because remodeling phenomena at the bone-implant interface are still poorly understood. The characterization of the biomechanical properties of newly formed bone tissue in the vicinity of implants at the microscopic scale is of importance in order to better understand the osseointegration process. The objective of this study is to investigate the potentiality of micro-Brillouin scattering techniques to differentiate mature and newly formed bone elastic properties following a multimodality approach using histological analysis. Coin-shaped Ti-6Al-4V implants were placed in vivo at a distance of 200 μm from rabbit tibia leveled cortical bone surface, leading to an initially empty cavity of 200 μm×4.4 mm. After 7 weeks of implantation, the bone samples were removed, fixed, dehydrated, embedded in methyl methacrylate, and sliced into 190 μm thick sections. Ultrasonic velocity measurements were performed using a micro-Brillouin scattering device within regions of interest (ROIs) of 10 μm diameter. The ROIs were located in newly formed bone tissue (within the 200 μm gap) and in mature bone tissue (in the cortical layer of the bone sample). The same section was then stained for histological analysis of the mineral content of the bone sample. The mean values of the ultrasonic velocities were equal to 4.97×10(-3) m/s in newly formed bone tissue and 5.31×10(-3) m/s in mature bone. Analysis of variance (p=2.42×10(-4)) tests revealed significant differences between the two groups of measurements. The standard deviation of the velocities was significantly higher in newly formed bone than in mature bone. Histological observations allow to confirm the accurate locations of the velocity measurements and showed a lower degree of mineralization in newly formed bone than in the mature cortical bone. The higher ultrasonic velocity measured in newly formed bone tissue compared with

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

    PubMed Central

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

    2016-01-01

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

  19. Blood and Interstitial flow in the hierarchical pore space architecture of bone tissue

    PubMed Central

    Cowin, Stephen C.; Cardoso, Luis

    2015-01-01

    There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. PMID:25666410

  20. Blood and interstitial flow in the hierarchical pore space architecture of bone tissue.

    PubMed

    Cowin, Stephen C; Cardoso, Luis

    2015-03-18

    There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Bio-inspired in situ crosslinking and mineralization of electrospun collagen scaffolds for bone tissue engineering.

    PubMed

    Dhand, Chetna; Ong, Seow Theng; Dwivedi, Neeraj; Diaz, Silvia Marrero; Venugopal, Jayarama Reddy; Navaneethan, Balchandar; Fazil, Mobashar H U T; Liu, Shouping; Seitz, Vera; Wintermantel, Erich; Beuerman, Roger W; Ramakrishna, Seeram; Verma, Navin K; Lakshminarayanan, Rajamani

    2016-10-01

    Bone disorders are the most common cause of severe long term pain and physical disability, and affect millions of people around the world. In the present study, we report bio-inspired preparation of bone-like composite structures by electrospinning of collagen containing catecholamines and Ca(2+). The presence of divalent cation induces simultaneous partial oxidative polymerization of catecholamines and crosslinking of collagen nanofibers, thus producing mats that are mechanically robust and confer photoluminescence properties. Subsequent mineralization of the mats by ammonium carbonate leads to complete oxidative polymerization of catecholamines and precipitation of amorphous CaCO3. The collagen composite scaffolds display outstanding mechanical properties with Young's modulus approaching the limits of cancellous bone. Biological studies demonstrate that human fetal osteoblasts seeded on to the composite scaffolds display enhanced cell adhesion, penetration, proliferation, differentiation and osteogenic expression of osteocalcin, osteopontin and bone matrix protein when compared to pristine collagen or tissue culture plates. Among the two catecholamines, mats containing norepinephrine displayed superior mechanical, photoluminescence and biological properties than mats loaded with dopamine. These smart multifunctional scaffolds could potentially be utilized to repair and regenerate bone defects and injuries.

  2. Biophysicochemical evaluation of chitosan-hydroxyapatite-marine sponge collagen composite for bone tissue engineering.

    PubMed

    Pallela, Ramjee; Venkatesan, Jayachandran; Janapala, Venkateswara Rao; Kim, Se-Kwon

    2012-02-01

    Tricomponent scaffold systems prepared by natural materials especially of marine origin are gaining much attention nowadays for the application in bone tissue engineering. A novel scaffold (Chi-HAp-MSCol) containing chitosan (Chi), hydroxyapatite (HAp) derived from Thunnus obesus bone and marine sponge (Ircinia fusca) collagen (MSCol) was prepared using freeze-drying and lyophilization method. This biomimetic scaffold, along with the Chi and Chi-HAp scaffolds were characterized biophysicochemically for their comparative significance in bone grafting applications. The structural composition of the chitosan, Chi-Hap, and Chi-HAp-MSCol scaffolds were characterized by Fourier Transform Infrared spectroscopy. The porosity, water uptake, and retention abilities of the composite scaffolds decreased, whereas Thermogravimetric and Differential Thermal Analyses results revealed the increase in thermal stability in the scaffold because of the highly stable HAp and MSCol. Homogeneous dispersion of HAp and MSCol in chitosan matrix with interconnected porosity of 60-180 μm (Chi-HAp) and 50-170 μm (Chi-HAp-MSCol) was observed by Scanning Electron Microscopy, X-ray diffraction, and optical microscopy. Cell proliferation in composite scaffolds was relatively higher than pure chitosan when observed by MTT assay and Hoechst staining in vitro using MG-63 cell line. These observations suggest that the novel Chi-HAp-MSCol composite scaffolds are promising biomaterials for matrix-based bone repair and bone augmentation. Copyright © 2011 Wiley Periodicals, Inc.

  3. Viral inactivation of human bone tissue using supercritical fluid extraction.

    PubMed

    Fages, J; Poirier, B; Barbier, Y; Frayssinet, P; Joffret, M L; Majewski, W; Bonel, G; Larzul, D

    1998-01-01

    A new bone tissue process using supercritical carbon dioxide fluid extraction (SFE) has been evaluated for its ability to inactivate or eliminate viruses. Four viruses, human immunodeficiency virus type 1 (HIV-1), Sindbis virus, polio Sabin type I virus, and pseudorabies virus (PRV), were exposed to four different processing steps. In addition to supercritical CO2, hydrogen peroxide, sodium hydroxide, and ethanol treatments were evaluated. The mean cumulated reduction factors (log10) for the four viruses exposed to these four steps were > 14.2 for HIV-1, > 18.2 for Sindbis virus, > 24.4 for poliovirus, and > 17.6 for PRV. The mean reduction factors obtained by the supercritical fluid extraction alone were > 4.0, > 4.3, > 6.6, and > 4.0, respectively. These results demonstrate that the SFE process is effective in inactivating viruses on human femoral heads, and provides a level of inactivation similar to that obtained by traditional cleaning methods. It is proposed that CO2 SFE be incorporated as a routine step in the processing of bone allografts for transplantation either to replace or supplement existing procedures.

  4. Photoacoustic and ultrasound imaging of cancellous bone tissue

    NASA Astrophysics Data System (ADS)

    Yang, Lifeng; Lashkari, Bahman; Tan, Joel W. Y.; Mandelis, Andreas

    2015-07-01

    We used ultrasound (US) and photoacoustic (PA) imaging modalities to characterize cattle trabecular bones. The PA signals were generated with an 805-nm continuous wave laser used for optimally deep optical penetration depth. The detector for both modalities was a 2.25-MHz US transducer with a lateral resolution of ˜1 mm at its focal point. Using a lateral pixel size much larger than the size of the trabeculae, raster scanning generated PA images related to the averaged values of the optical and thermoelastic properties, as well as density measurements in the focal volume. US backscatter yielded images related to mechanical properties and density in the focal volume. The depth of interest was selected by time-gating the signals for both modalities. The raster scanned PA and US images were compared with microcomputed tomography (μCT) images averaged over the same volume to generate similar spatial resolution as US and PA. The comparison revealed correlations between PA and US modalities with the mineral volume fraction of the bone tissue. Various features and properties of these modalities such as detectable depth, resolution, and sensitivity are discussed.

  5. Processing and characterization of innovative scaffolds for bone tissue engineering.

    PubMed

    Bellucci, D; Chiellini, F; Ciardelli, G; Gazzarri, M; Gentile, P; Sola, A; Cannillo, V

    2012-06-01

    A new protocol, based on a modified replication method, is proposed to obtain bioactive glass scaffolds. The main feature of these samples, named "shell scaffolds", is their external surface that, like a compact and porous shell, provides both high permeability to fluids and mechanical support. In this work, two different scaffolds were prepared using the following slurry components: 59 % water, 29 % 45S5 Bioglass(®) and 12 % polyvinylic binder and 51 % water, 34 % 45S5 Bioglass(®), 10 % polyvinylic binder and 5 % polyethylene. All the proposed samples were characterized by a widespread microporosity and an interconnected macroporosity, with a total porosity of 80 % vol. After immersion in a simulated body fluid (SBF), the scaffolds showed strong ability to develop hydroxyapatite, enhanced by the high specific surface of the porous systems. Moreover preliminary biological evaluations suggested a promising role of the shell scaffolds for applications in bone tissue regeneration. As regards the mechanical behaviour, the shell scaffolds could be easily handled without damages, due to their resistant external surface. More specifically, they possessed suitable mechanical properties for bone regeneration, as proved by compression tests performed before and after immersion in SBF.

  6. Chitosan and alginate scaffolds for bone tissue regeneration.

    PubMed

    Olmez, S S; Korkusuz, P; Bilgili, H; Senel, S

    2007-06-01

    Polymeric scaffold for tissue regeneration was developed for veterinary applications. Oxytetracycline hydrochloride (OTC), which is a widely used antibiotic in veterinary medicine was chosen as the model compound. Gel formulations using chitosan and alginate were prepared in distilled water or in 1% (v/v) acetic acid solution. Sponges were also prepared by a freeze-drying process. Tripolyphosphate was used for cross-linking. Viscosity was decreased in the presence of OTC in chitosan gels whereas no difference was found with alginate gels. All gels showed pseudoplastic behaviour. Water absorption capacity was highest with chitosan/alginate sponges. The solvent used for preparation of the chitosan gels was found to affect the release of OTC. The release of OTC from the sponges was increased by cross-linking. Chitosan/alginate sponges showed the slowest and lowest drug release among the developed sponge formulations in this study. The formulations were found to be biocompatible, inducing no adverse reaction in vivo on surgically formed bone defects of radius of rabbits. The level of organization of the remodelled new bone in the treatment groups was better than that of control. Incorporation of OTC into formulations did not show any considerable enhancing effect.

  7. Photoacoustic and ultrasound imaging of cancellous bone tissue.

    PubMed

    Yang, Lifeng; Lashkari, Bahman; Tan, Joel W Y; Mandelis, Andreas

    2015-07-01

    We used ultrasound (US) and photoacoustic (PA) imaging modalities to characterize cattle trabecular bones. The PA signals were generated with an 805-nm continuous wave laser used for optimally deep optical penetration depth. The detector for both modalities was a 2.25-MHz US transducer with a lateral resolution of ~1 mm at its focal point. Using a lateral pixel size much larger than the size of the trabeculae, raster scanning generated PA images related to the averaged values of the optical and thermoelastic properties, as well as density measurements in the focal volume. US backscatter yielded images related to mechanical properties and density in the focal volume. The depth of interest was selected by time-gating the signals for both modalities. The raster scanned PA and US images were compared with microcomputed tomography (μCT) images averaged over the same volume to generate similar spatial resolution as US and PA. The comparison revealed correlations between PA and US modalities with the mineral volume fraction of the bone tissue. Various features and properties of these modalities such as detectable depth, resolution, and sensitivity are discussed.

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

    PubMed

    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 < 0.05) among all 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.

  9. Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Feng, Kai

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

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

    PubMed Central

    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. PMID:26380018

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

    PubMed

    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.

  12. Improved Prediction of Rat Cortical Bone Mechanical Behavior using Composite Beam Theory to Integrate Tissue Level Properties

    PubMed Central

    Kim, Grace; Boskey, Adele L.; Baker, Shefford P.; van der Meulen, Marjolein C. H.

    2012-01-01

    Tissue level characteristics of bone can be measured by nanoindentation and microspectroscopy, but are challenging to translate to whole bone mechanical behavior in this hierarchically structured material. The current study calculated weighted section modului from microCT attenuation values based on tissue level relationships (Zlin,a and Zlin,b) between mineralization and material properties to predict whole bone mechanical behavior. Zlin,a was determined using the equation of the best fit linear regression between nanoindentation indentation modulus and mineral:matrix ratio from Raman spectroscopy. To better represent the modulus of unmineralized tissue, a second linear regression with the intercept fixed at 0 was used to calculate Zlin,b. The predictive capability of the weighted section moduli calculated using a tissue level relationship were compared with average tissue level properties and weighted section moduli calculated using an apparent level relationship (Zexp) between Young’s Modulus and mineralization. A range of bone mineralization was created using vitamin D deficiency in growing rats. After 10 weeks, left femurs were scanned using microCT and tested to failure in 3 point bending. Contralateral limbs were used for co-localized tissue level mechanical properties by nanoindentation and compositional measurements by Raman microspectroscopy. Vitamin D deficiency reduced whole bone stiffness and strength by ~35% and ~30%, respectively, but only reduced tissue mineral density by ~10% compared with Controls. Average tissue level properties did not correlate with whole bone mechanical behavior while Zlin,a, Zlin,b, and Zexp predicted 54%, 66%, and 80% of the failure moment respectively. This study demonstrated that in a model for varying mineralization, the composite beam model in this paper is an improved method to extrapolate tissue level data to macro-scale mechanical behavior. PMID:23021607

  13. Hydroxyapatite scaffolds for bone tissue engineering made by 3D printing.

    PubMed

    Leukers, Barbara; Gülkan, Hülya; Irsen, Stephan H; Milz, Stefan; Tille, Carsten; Schieker, Matthias; Seitz, Hermann

    2005-12-01

    Nowadays, there is a significant need for synthetic bone replacement materials used in bone tissue engineering (BTE). Rapid prototyping and especially 3D printing is a suitable technique to create custom implants based on medical data sets. 3D printing allows to fabricate scaffolds based on Hydroxyapatite with complex internal structures and high resolution. To determine the in vitro behaviour of cells cultivated on the scaffolds, we designed a special test-part. MC3T3-E1 cells were seeded on the scaffolds and cultivated under static and dynamic setups. Histological evaluation was carried out to characterise the cell ingrowth. In summary, the dynamic cultivation method lead to a stronger population compared to the static cultivation method. The cells proliferated deep into the structure forming close contact to Hydroxyapatite granules.

  14. Three-dimensional fiber deposition of cell-laden, viable, patterned constructs for bone tissue printing.

    PubMed

    Fedorovich, Natalja E; De Wijn, Joost R; Verbout, Abraham J; Alblas, Jacqueline; Dhert, Wouter J A

    2008-01-01

    Organ or tissue printing, a novel approach in tissue engineering, creates layered, cell-laden hydrogel scaffolds with a defined three-dimensional (3D) structure and organized cell placement. In applying the concept of tissue printing for the development of vascularized bone grafts, the primary focus lies on combining endothelial progenitors and bone marrow stromal cells (BMSCs). Here we characterize the applicability of 3D fiber deposition with a plotting device, Bioplotter, for the fabrication of spatially organized, cell-laden hydrogel constructs. The viability of printed BMSCs was studied in time, in several hydrogels, and extruded from different needle diameters. Our findings indicate that cells survive the extrusion and that their subsequent viability was not different from that of unprinted cells. The applied extrusion conditions did not affect cell survival, and BMSCs could subsequently differentiate along the osteoblast lineage. Furthermore, we were able to combine two distinct cell populations within a single scaffold by exchanging the printing syringe during deposition, indicating that this 3D fiber deposition system is suited for the development of bone grafts containing multiple cell types.

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

    PubMed Central

    Cheng, Tegan L; Murphy, Ciara M; Ravarian, Roya; Dehghani, Fariba; Little, David G; Schindeler, Aaron

    2015-01-01

    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. PMID:26668709

  16. Free Vascularized Medial Femoral Condyle Structural Flaps for Septic Terminal Digital Bone Loss.

    PubMed

    Henry, Mark

    2015-12-01

    A unique clinical problem exists when the majority of distal bone stock in a digit is destroyed by osteomyelitis, leaving a residual soft tissue envelope with tenuous, random perfusion surrounding a nidus of scar tissue. Pulp pinch is lost in the absence of bony support, and limited options exist. Apart from toe transfer or revision amputation with shortening, non-vascularized bone grafting inside the residual soft tissue envelope risks graft resorption and reactivation of infection. The purpose of this investigation was to evaluate the clinical outcomes of free vascularized medial femoral condyle structural bone flaps to restore lost pulp pinch in such cases. Nine patients (8 males, 1 female) with a mean age of 43 years sustained extensive terminal bone loss near digital tips following osteomyelitis. The mean length of bone defect was 28 mm (± 8.4). The patients were reconstructed at a mean of 12 weeks from initial trauma/infection, having undergone a mean of two prior surgeries. A structural block of vascularized bone from the medial femoral condyle replaced the missing bone at the digital tip defect, temporarily fixed with K-wires. The bone flap was encased by the residual soft tissue envelope after removing scar tissue from the prior trauma and infection. All bone flaps incorporated fully, restoring pulp pinch function to the respective digits with a mean time to union of 8.6 (± 2.1) weeks; range 6-11 weeks. With few alternative solutions able to address this unique and difficult problem, the structural block of vascularized bone proved able to resist resorption, nonunion, and reactivation of infection; the problems normally encountered under this scenario.

  17. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo.

    PubMed

    Chang, Ming K; Raggatt, Liza-Jane; Alexander, Kylie A; Kuliwaba, Julia S; Fazzalari, Nicola L; Schroder, Kate; Maylin, Erin R; Ripoll, Vera M; Hume, David A; Pettit, Allison R

    2008-07-15

    Resident macrophages are an integral component of many tissues and are important in homeostasis and repair. This study examines the contribution of resident tissue macrophages to bone physiology. Using immunohistochemistry, we showed that a discrete population of resident macrophages, OsteoMacs, was intercalated throughout murine and human osteal tissues. OsteoMacs were distributed among other bone lining cells within both endosteum and periosteum. Furthermore, OsteoMacs were coisolated with osteoblasts in murine bone explant and calvarial preparations. OsteoMacs made up 15.9% of calvarial preparations and persisted throughout standard osteoblast differentiation cultures. Contrary to previous studies, we showed that it was OsteoMacs and not osteoblasts within these preparations that responded to pathophysiological concentrations of LPS by secreting TNF. Removal of OsteoMacs from calvarial cultures significantly decreased osteocalcin mRNA induction and osteoblast mineralization in vitro. In a Transwell coculture system of enriched osteoblasts and macrophages, we demonstrated that macrophages were required for efficient osteoblast mineralization in response to the physiological remodeling stimulus, elevated extracellular calcium. Notably, OsteoMacs were closely associated with areas of bone modeling in situ, forming a distinctive canopy structure covering >75% of mature osteoblasts on diaphyseal endosteal surfaces in young growing mice. Depletion of OsteoMacs in vivo using the macrophage-Fas-induced apoptosis (MAFIA) mouse caused complete loss of osteoblast bone-forming surface at this modeling site. Overall, we have demonstrated that OsteoMacs are an integral component of bone tissues and play a novel role in bone homeostasis through regulating osteoblast function. These observations implicate OsteoMacs, in addition to osteoclasts and osteoblasts, as principal participants in bone dynamics.

  18. Hard tissue regeneration using bone substitutes: an update on innovations in materials

    PubMed Central

    Sarkar, Swapan Kumar

    2015-01-01

    Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues. PMID:25995658

  19. Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study.

    PubMed

    Casazza, K; Hanks, L J; Hidalgo, B; Hu, H H; Affuso, O

    2012-01-01

    Mechanical stimulation is necessary for maximization of geometrical properties of bone mineralization contributing to long-term strength. The amount of mineralization in bones has been reciprocally related to volume of bone marrow adipose tissue and this relationship is suggested to be an independent predictor of fracture. Physical activity represents an extrinsic factor that impacts both mineralization and marrow volume exerting permissive capacity of the growing skeleton to achieve its full genetic potential. Because geometry- and shape-determining processes primarily manifest during the linear growth period, the accelerated structural changes accompanying early childhood (ages 3 to 6 y) may have profound impact on lifelong bone health. The objective of this pilot study was to determine if a short-term physical activity intervention in young children would result in augmentation of geometric properties of bone. Three days per week the intervention group (n=10) participated in 30 min of moderate intensity physical activity, such as jumping, hopping and running, and stretching activities, whereas controls (n=10) underwent usual activities during the 10-week intervention period. Femoral bone marrow adipose tissue volume and total body composition were assessed by magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively, at baseline and after 10 weeks. Although after 10-weeks, intergroup differences were not observed, a significant decrease in femoral marrow adipose tissue volume was observed in those participating in physical activity intervention. Our findings suggest that physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization.

  20. Nanohydroxyapatite/poly(ester urethane) scaffold for bone tissue engineering.

    PubMed

    Boissard, C I R; Bourban, P-E; Tami, A E; Alini, M; Eglin, D

    2009-11-01

    Biodegradable viscoelastic poly(ester urethane)-based scaffolds show great promise for tissue engineering. In this study, the preparation of hydroxyapatite nanoparticles (nHA)/poly(ester urethane) composite scaffolds using a salt-leaching-phase inverse process is reported. The dispersion of nHA microaggregates in the polymer matrix were imaged by microcomputed X-ray tomography, allowing a study of the effect of the nHA mass fraction and process parameters on the inorganic phase dispersion, and ultimately the optimization of the preparation method. How the composite scaffold's geometry and mechanical properties change with the nHA mass fraction and the process parameters were assessed. Increasing the amount of nHA particles in the composite scaffold decreased the porosity, increased the wall thickness and consequently decreased the pore size. The Young's modulus of the poly(ester urethane) scaffold was improved by 50% by addition of 10 wt.% nHA (from 0.95+/-0.5 to 1.26+/-0.4 MPa), while conserving poly(ester urethane) viscoelastic properties and without significant changes in the scaffold macrostructure. Moreover, the process permitted the inclusion of nHA particles not only in the poly(ester urethane) matrix, but also at the surface of the scaffold pores, as shown by scanning electron microscopy. nHA/poly(ester urethane) composite scaffolds have great potential as osteoconductive constructs for bone tissue engineering.

  1. Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

    PubMed Central

    Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

    2012-01-01

    There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

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

    PubMed

    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

  3. Tooth and bone deformation: structure and material properties by ESPI

    NASA Astrophysics Data System (ADS)

    Zaslansky, Paul; Shahar, Ron; Barak, Meir M.; Friesem, Asher A.; Weiner, Steve

    2006-08-01

    In order to understand complex-hierarchical biomaterials such as bones and teeth, it is necessary to relate their structure and mechanical-properties. We have adapted electronic speckle pattern-correlation interferometry (ESPI) to make measurements of deformation of small water-immersed specimens of teeth and bones. By combining full-field ESPI with precision mechanical loading we mapped sub-micron displacements and determined material-properties of the samples. By gradually and elastically compressing the samples, we compensate for poor S/N-ratios and displacement differences of about 100nm were reliably determined along samples just 2~3mm long. We produced stress-strain curves well within the elastic performance range of these materials under biologically relevant conditions. For human tooth-dentin, Young's modulus in inter-dental areas of the root is 40% higher than on the outer sides. For cubic equine bone samples the compression modulus of axial orientations is about double the modulus of radial and tangential orientations (20 GPa versus 10 GPa respectively). Furthermore, we measured and reproduced a surprisingly low Poisson's ratio, which averaged about 0.1. Thus the non-contact and non-destructive measurements by ESPI produce high sensitivity analyses of mechanical properties of mineralized tissues. This paves the way for mapping deformation-differences of various regions of bones, teeth and other biomaterials.

  4. Targeting gene expression during the early bone healing period in the mandible: A base for bone tissue engineering.

    PubMed

    Beck-Broichsitter, Benedicta E; Werk, Anneke N; Smeets, Ralf; Gröbe, Alexander; Heiland, Max; Cascorbi, Ingolf; Wiltfang, Jörg; Häsler, Robert; Becker, Stephan T

    2015-10-01

    Although bone tissue engineering techniques have become more and more sophisticated than in the past, natural bone healing mechanisms have not been sufficiently considered for further improvement of these techniques so far. We used an established animal model with transcriptome analysis to generate an unbiased picture of early bone healing to support tissue engineering concepts. In 30 Wistar rats, a 3-mm bone defect was created in the mandibular angle. Tissue was sampled at 5, 10, and 15 days, and the former defect area was excised to undergo transcriptome analysis after RNA extraction. Five differentially expressed genes were further evaluated with reverse transcription-polymerase chain reaction (rt-PCR). Transcriptome analysis revealed 2467 significantly over- and under-expressed transcripts after 5 days and 2265 after 15 days of bone healing, respectively. Validation via rt-PCR confirmed overexpression of osteoactivin, angiopoietin-like factor-4, and metallomatrix proteinase-9 and underexpression of mastcellprotease-10 and proteoglycane-2 in comparison to values in the control group. This systematic genome-wide transcriptome analysis helps to decipher the physiological mechanisms behind physiological bone healing. The exemplary depiction of 5 genes demonstrates the great complexity of metabolic processes during early bone healing. Here, BMP-2 signaling pathways and local hypoxia play decisive roles in bone formation. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  6. Imaging stem cell distribution, growth, migration, and differentiation in 3-D scaffolds for bone tissue engineering using mesoscopic fluorescence tomography.

    PubMed

    Tang, Qinggong; Piard, Charlotte; Lin, Jonathan; Nan, Kai; Guo, Ting; Caccamese, John; Fisher, John; Chen, Yu

    2017-09-16

    Regenerative medicine has emerged as an important discipline that aims to repair injury or replace damaged tissues or organs by introducing living cells or functioning tissues. Successful regenerative medicine strategies will likely depend upon a simultaneous optimization strategy for the design of biomaterials, cell-seeding methods, cell-biomaterial interactions and molecular signaling within the engineered tissues. It remains a challenge to image three-dimensional (3-D) structures and functions of the cell-seeded scaffold in mesoscopic scale (>2∼3 mm). In this study, we utilized angled fluorescence laminar optical tomography (aFLOT), which allows depth-resolved molecular characterization of engineered tissues in 3-D to investigate cell viability, migration and bone mineralization within bone tissue engineering scaffolds in situ. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Comparison of structural, architectural and mechanical aspects of cellular and acellular bone in two teleost fish.

    PubMed

    Cohen, Liat; Dean, Mason; Shipov, Anna; Atkins, Ayelet; Monsonego-Ornan, Efrat; Shahar, Ron

    2012-06-01

    The histological diversity of the skeletal tissues of fishes is impressive compared with that of other vertebrate groups, yet our understanding of the functional consequences of this diversity is limited. In particular, although it has been known since the mid-1800s that a large number of fish species possess acellular bones, the mechanical advantages and consequences of this structural characteristic - and therefore the nature of the evolution of this feature - remain unclear. Although several studies have examined the material properties of fish bone, these have used a variety of techniques and there have been no direct contrasts of acellular and cellular bone. We report on a comparison of the structural and mechanical properties of the ribs and opercula between two freshwater fish - the common carp Cyprinus carpio (a fish with cellular bone) and the tilapia Oreochromis aureus (a fish with acellular bone). We used light microscopy to show that the bones in both fish species exhibit poor blood supply and possess discrete tissue zones, with visible layering suggesting differences in the underlying collagen architecture. We performed identical micromechanical testing protocols on samples of the two bone types to determine the mechanical properties of the bone material of opercula and ribs. Our data support the consensus of literature values, indicating that Young's moduli of cellular and acellular bones are in the same range, and lower than Young's moduli of the bones of mammals and birds. Despite these similarities in mechanical properties between the bone tissues of the fish species tested here, cellular bone had significantly lower mineral content than acellular bone; furthermore, the percentage ash content and bone mineral density values (derived from micro-CT scans) show that the bone of these fishes is less mineralized than amniote bone. Although we cannot generalize from our data to the numerous remaining teleost species, the results presented here suggest

  8. Method and system for in vivo measurement of bone tissue using a two level energy source

    NASA Technical Reports Server (NTRS)

    Cameron, J. R.; Judy, P. F. (Inventor)

    1976-01-01

    Methods and apparatus are provided for radiologically determining the bone mineral content of living human bone tissue independently of the concurrent presence of adipose and other soft tissues. A target section of the body of the subject is irradiated with a beam of penetrative radiations of preselected energy to determine the attenuation of such beam with respect to the intensity of each of two radiations of different predetermined energy levels. The resulting measurements are then employed to determine bone mineral content.