Sample records for bone tissue structure

  1. 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

  2. Nanocomposites for bone tissue regeneration.

    PubMed

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

    2013-04-01

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

  3. Specialized connective tissue: bone, the structural framework of the upper extremity

    PubMed Central

    Weatherholt, Alyssa M.; Fuchs, Robyn K.; Warden, Stuart J.

    2011-01-01

    Bone is a connective tissue containing cells, fibers and ground substance. There are many functions in the body in which the bone participates, such as storing minerals, providing internal support, protecting vital organs, enabling movement, and providing attachment sites for muscles and tendons. Bone is unique because its collagen framework absorbs energy, while the mineral encased within the matrix allows bone to resist deformation. This article provides an overview of the structure and function of bone tissue from a macroscopic to microscopic level and discusses the physiological processes contributing to upper extremity bone health. It concludes by discussing common conditions influencing upper extremity bone health. PMID:22047807

  4. Spiral-structured, nanofibrous, 3D scaffolds for bone tissue engineering.

    PubMed

    Wang, Junping; Valmikinathan, Chandra M; Liu, Wei; Laurencin, Cato T; Yu, Xiaojun

    2010-05-01

    Polymeric nanofiber matrices have already been widely used in tissue engineering. However, the fabrication of nanofibers into complex three-dimensional (3D) structures is restricted due to current manufacturing techniques. To overcome this limitation, we have incorporated nanofibers onto spiral-structured 3D scaffolds made of poly (epsilon-caprolactone) (PCL). The spiral structure with open geometries, large surface areas, and porosity will be helpful for improving nutrient transport and cell penetration into the scaffolds, which are otherwise limited in conventional tissue-engineered scaffolds for large bone defects repair. To investigate the effect of structure and fiber coating on the performance of the scaffolds, three groups of scaffolds including cylindrical PCL scaffolds, spiral PCL scaffolds (without fiber coating), and spiral-structured fibrous PCL scaffolds (with fiber coating) have been prepared. The morphology, porosity, and mechanical properties of the scaffolds have been characterized. Furthermore, human osteoblast cells are seeded on these scaffolds, and the cell attachment, proliferation, differentiation, and mineralized matrix deposition on the scaffolds are evaluated. The results indicated that the spiral scaffolds possess porosities within the range of human trabecular bone and an appropriate pore structure for cell growth, and significantly lower compressive modulus and strength than cylindrical scaffolds. When compared with the cylindrical scaffolds, the spiral-structured scaffolds demonstrated enhanced cell proliferation, differentiation, and mineralization and allowed better cellular growth and penetration. The incorporation of nanofibers onto spiral scaffolds further enhanced cell attachment, proliferation, and differentiation. These studies suggest that spiral-structured nanofibrous scaffolds may serve as promising alternatives for bone tissue engineering applications. Copyright 2009 Wiley Periodicals, Inc.

  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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Advances in bionanomaterials for bone tissue engineering.

    PubMed

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

    2013-01-01

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

  7. Nanoparticles for bone tissue engineering.

    PubMed

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

    2017-05-01

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

  8. [Principles of bone tissue structures interaction with full removable dentures fixed on intraosseous implantates modelling].

    PubMed

    Shashmurina, V R; Chumachenko, E N; Olesova, V N; Volozhin, A I

    2008-01-01

    Math modelling "removable dentures-implantate-bone" with size and density of bone tissue as variables was created. It allowed to study biomechanical bases of mandibular bone tissue structures interaction with full removable dentures of different constructions and fixed on intraosseous implantates. Analysis of the received data showed that in the majority of cases it was expedient to recommend 3 bearing (abutments) system of denture making. Rest on 4 and more implantates was appropriate for patients with reduced density of spongy bone and significant mandibular bone atrophy. 2 abutment system can be used in patients with high density of spongy bone and absence of mandibular bone atrophy.

  9. Dose in bone and tissue near bone-tissue interface from electron beam.

    PubMed

    Shiu, A S; Hogstrom, K R

    1991-08-01

    This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone-tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA)-hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for

  10. 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.

  11. 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

  12. 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.

  13. [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.

  14. 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

  15. 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.

  16. 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

  17. Mechanical control of tissue-engineered bone.

    PubMed

    Hung, Ben P; Hutton, Daphne L; Grayson, Warren L

    2013-01-31

    Bone is a load-bearing tissue and physical forces play key roles in the development and maintenance of its structure. Mechanical cues can stimulate the expression of an osteogenic phenotype, enhance matrix and mineral deposition, and influence tissue organization to improve the functional outcome of engineered bone grafts. In recent years, a number of studies have investigated the effects of biophysical forces on the bone formation properties of osteoprogenitor cells. The application of physiologically relevant stimuli to tissue-engineered bone may be determined through observation and understanding of forces to which osteoblasts, osteoclasts, and osteocytes are exposed in native bone. Subsequently, these cues may be parameterized and their effects studied in well-defined in vitro systems. The osteo-inductive effects of three specific mechanical cues - shear stress, substrate rigidity, and nanotopography - on cells cultured in monolayer or in three-dimensional biomaterial scaffolds in vitro are reviewed. Additionally, we address the time-dependent effects of mechanical cues on vascular infiltration and de novo bone formation in acellular scaffolds implanted into load-bearing sites in vivo. Recent studies employing cutting-edge advances in biomaterial fabrication and bioreactor design have provided key insights into the role of mechanical cues on cellular fate and tissue properties of engineered bone grafts. By providing mechanistic understanding, future studies may go beyond empirical approaches to rational design of engineering systems to control tissue development.

  18. 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

  19. Composition and structure of porcine digital flexor tendon-bone insertion tissues.

    PubMed

    Chandrasekaran, Sandhya; Pankow, Mark; Peters, Kara; Huang, Hsiao-Ying Shadow

    2017-11-01

    Tendon-bone insertion is a functionally graded tissue, transitioning from 200 MPa tensile modulus at the tendon end to 20 GPa tensile modulus at the bone, across just a few hundred micrometers. In this study, we examine the porcine digital flexor tendon insertion tissue to provide a quantitative description of its collagen orientation and mineral concentration by using Fast Fourier Transform (FFT) based image analysis and mass spectrometry, respectively. Histological results revealed uniformity in global collagen orientation at all depths, indicative of mechanical anisotropy, although at mid-depth, the highest fiber density, least amount of dispersion, and least cellular circularity were evident. Collagen orientation distribution obtained through 2D FFT of histological imaging data from fluorescent microscopy agreed with past measurements based on polarized light microscopy. Results revealed global fiber orientation across the tendon-bone insertion to be preserved along direction of physiologic tension. Gradation in the fiber distribution orientation index across the insertion was reflective of a decrease in anisotropy from the tendon to the bone. We provided elemental maps across the fibrocartilage for its organic and inorganic constituents through time-of-flight secondary ion mass spectrometry (TOF-SIMS). The apatite intensity distribution from the tendon to bone was shown to follow a linear trend, supporting past results based on Raman microprobe analysis. The merit of this study lies in the image-based simplified approach to fiber distribution quantification and in the high spatial resolution of the compositional analysis. In conjunction with the mechanical properties of the insertion tissue, fiber, and mineral distribution results for the insertion from this may potentially be incorporated into the development of a structural constitutive approach toward computational modeling. Characterizing the properties of the native insertion tissue would provide the

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

    PubMed

    Shadjou, Nasrin; Hasanzadeh, Mohammad

    2015-10-01

    Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Fundamentals of biomechanics in tissue engineering of bone.

    PubMed

    Athanasiou, K A; Zhu, C; Lanctot, D R; Agrawal, C M; Wang, X

    2000-08-01

    The objective of this review is to provide basic information pertaining to biomechanical aspects of bone as they relate to tissue engineering. The review is written for the general tissue engineering reader, who may not have a biomechanical engineering background. To this end, biomechanical characteristics and properties of normal and repair cortical and cancellous bone are presented. Also, this chapter intends to describe basic structure-function relationships of these two types of bone. Special emphasis is placed on salient classical and modern testing methods, with both material and structural properties described.

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

    PubMed

    Griffin, M F; Kalaskar, D M; Seifalian, A; Butler, P E

    2016-01-01

    Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Future studies to improve the application of nanomaterials for bone tissue engineering are needed.

  3. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies.

    PubMed

    Porter, Joshua R; Ruckh, Timothy T; Popat, Ketul C

    2009-01-01

    Critical-sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue-engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical-sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF-betas, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Biomimetic Materials and Fabrication Approaches for Bone Tissue Engineering.

    PubMed

    Kim, Hwan D; Amirthalingam, Sivashanmugam; Kim, Seunghyun L; Lee, Seunghun S; Rangasamy, Jayakumar; Hwang, Nathaniel S

    2017-12-01

    Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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.

  10. The materials used in bone tissue engineering

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

    Tereshchenko, V. P., E-mail: tervp@ngs.ru; Kirilova, I. A.; Sadovoy, M. A.

    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 aremore » 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.« less

  11. 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

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

    PubMed

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

    2015-01-01

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

  13. Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

    PubMed

    Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

    Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

  14. 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.

  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. 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.

  17. Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces.

    PubMed

    Boys, Alexander J; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J; Estroff, Lara A

    2017-09-01

    Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors.

  18. 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

  19. Chitosan Composites for Bone Tissue Engineering—An Overview

    PubMed Central

    Venkatesan, Jayachandran; Kim, Se-Kwon

    2010-01-01

    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 protheses to treat the loss or failure of an organ or bone tissue. Chitosan has played a major role in bone tissue engineering over the last two decades, being a natural polymer obtained from chitin, which forms a major component of crustacean exoskeleton. In recent years, considerable attention has been given to chitosan composite materials and their applications in the field of bone tissue engineering due to its minimal foreign body reactions, an intrinsic antibacterial nature, biocompatibility, biodegradability, and the ability to be molded into various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. The composite of chitosan including hydroxyapatite is very popular because of the biodegradability and biocompatibility in nature. Recently, grafted chitosan natural polymer with carbon nanotubes has been incorporated to increase the mechanical strength of these composites. Chitosan composites are thus emerging as potential materials for artificial bone and bone regeneration in tissue engineering. Herein, the preparation, mechanical properties, chemical interactions and in vitro activity of chitosan composites for bone tissue engineering will be discussed. PMID:20948907

  20. Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

    PubMed Central

    Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

    2017-01-01

    Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

  1. Chitosan based nanofibers in bone tissue engineering.

    PubMed

    Balagangadharan, K; Dhivya, S; Selvamurugan, N

    2017-11-01

    Bone tissue engineering involves biomaterials, cells and regulatory factors to make biosynthetic bone grafts with efficient mineralization for regeneration of fractured or damaged bones. Out of all the techniques available for scaffold preparation, electrospinning is given priority as it can fabricate nanostructures. Also, electrospun nanofibers possess unique properties such as the high surface area to volume ratio, porosity, stability, permeability and morphological similarity to that of extra cellular matrix. Chitosan (CS) has a significant edge over other materials and as a graft material, CS can be used alone or in combination with other materials in the form of nanofibers to provide the structural and biochemical cues for acceleration of bone regeneration. Hence, this review was aimed to provide a detailed study available on CS and its composites prepared as nanofibers, and their associated properties found suitable for bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism

    PubMed Central

    Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

    2017-01-01

    Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor–host cell dynamics, tumor tropism, and hematopoietic cell transplantation. PMID:28484009

  3. In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.

    PubMed

    Shih, Yu-Ru; Kang, Heemin; Rao, Vikram; Chiu, Yu-Jui; Kwon, Seong Keun; Varghese, Shyni

    2017-05-23

    Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor-host cell dynamics, tumor tropism, and hematopoietic cell transplantation.

  4. 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

  5. Electrospun nanofibrous 3D scaffold for bone tissue engineering.

    PubMed

    Eap, Sandy; Ferrand, Alice; Palomares, Carlos Mendoza; Hébraud, Anne; Stoltz, Jean-François; Mainard, Didier; Schlatter, Guy; Benkirane-Jessel, Nadia

    2012-01-01

    Tissue engineering aims at developing functional substitutes for damaged tissues by mimicking natural tissues. In particular, tissue engineering for bone regeneration enables healing of some bone diseases. Thus, several methods have been developed in order to produce implantable biomaterial structures that imitate the constitution of bone. Electrospinning is one of these methods. This technique produces nonwoven scaffolds made of nanofibers which size and organization match those of the extracellular matrix. Until now, seldom electrospun scaffolds were produced with thickness exceeding one millimeter. This article introduces a new kind of electrospun membrane called 3D scaffold of thickness easily exceeding one centimeter. The manufacturing involves a solution of poly(ε-caprolactone) in DMF/DCM system. The aim is to establish parameters for electrospinning in order to characterize these 3D scaffolds and, establish whether such scaffolds are potentially interesting for bone regeneration.

  6. Recent advances in bone tissue engineering scaffolds

    PubMed Central

    Bose, Susmita; Roy, Mangal; Bandyopadhyay, Amit

    2012-01-01

    Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, biodegradable materials that harbor different growth factors, drugs, genes or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. PMID:22939815

  7. Cell-scaffold interactions in the bone tissue engineering triad.

    PubMed

    Murphy, Ciara M; O'Brien, Fergal J; Little, David G; Schindeler, Aaron

    2013-09-20

    Bone tissue engineering has emerged as one of the leading fields in tissue engineering and regenerative medicine. The success of bone tissue engineering relies on understanding the interplay between progenitor cells, regulatory signals, and the biomaterials/scaffolds used to deliver them--otherwise known as the tissue engineering triad. This review will discuss the roles of these fundamental components with a specific focus on the interaction between cell behaviour and scaffold structural properties. In terms of scaffold architecture, recent work has shown that pore size can affect both cell attachment and cellular invasion. Moreover, different materials can exert different biomechanical forces, which can profoundly affect cellular differentiation and migration in a cell type specific manner. Understanding these interactions will be critical for enhancing the progress of bone tissue engineering towards clinical applications.

  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. Brown Adipose Tissue and Its Relationship to Bone Structure in Pediatric Patients

    PubMed Central

    Ponrartana, Skorn; Aggabao, Patricia C.; Hu, Houchun H.; Aldrovandi, Grace M.; Wren, Tishya A. L.

    2012-01-01

    Context: Emerging evidence suggests a possible link between brown adipose tissue (BAT) and bone metabolism. Objective: The objective of this study was to examine the relationships between BAT and bone cross-sectional dimensions in children and adolescents. Design: This was a cross-sectional study. Setting: The study was conducted at a pediatric referral center. Patients: Patients included 40 children and teenagers (21 males and 19 females) successfully treated for pediatric malignancies. Interventions: There were no interventions. Main Outcome Measures: The volume of BAT was determined by fluorodeoxyglucose-positron emission tomography/computed tomography. Measures of the cross-sectional area and cortical bone area and measures of thigh musculature and sc fat were determined at the midshaft of the femur. Results: Regardless of sex, there were significant correlations seen between BAT volume and the cross-sectional dimensions of the bone (r values between 0.68 and 0.77; all P ≤ 0 .001). Multiple regression analyses indicated that the volume of BAT predicted femoral cross-sectional area and cortical bone area, even after accounting for height, weight, and gender. The addition of muscle as an independent variable increased the predictive power of the model but significantly decreased the contribution of BAT. Conclusions: The volume of BAT is positively associated with the amount of bone and the cross-sectional size of the femur in children and adolescents. This relation between BAT and bone structure could, at least in part, be mediated by muscle. PMID:22593587

  10. 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

  11. 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

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

    PubMed

    Sakai, Akinori

    2011-04-01

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

  13. Bionic Design, Materials and Performance of Bone Tissue Scaffolds

    PubMed Central

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

    2017-01-01

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

  14. Bionic Design, Materials and Performance of Bone Tissue Scaffolds.

    PubMed

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

    2017-10-17

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

  15. 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.

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

    PubMed Central

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

    2017-01-01

    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 humans 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 (2×2×2mm) 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 seven 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 orthotropic elastic behavior where the highest stiffness was in the axial direction followed by the transverse and the radial directions respectively (21.6±3.3 GPa, 17.6±3.0 GPa and 14.9±1.9 GPa respectively). Our results also revealed a slight non-significant decrease in bone stiffness after seven days. Finally, our sample size allowed us to establish that population variance was much bigger in the axial direction compared to the radial direction which potentially reflects bone adaptation to the large diversity in loading activity between individuals in the loading direction (axial) compared to the normal (radial) direction. This study confirms that the well mechanically-studied human transverse-isotropic osteonal bone is just one possible functional adaptation of bone tissue and that other vertebrate

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

    PubMed

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

    2018-01-01

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

  18. 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.

  19. 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

  20. Extracorporeal human bone-like tissue generation

    PubMed Central

    Rosenberg, N.; Rosenberg, O.

    2012-01-01

    Objectives The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation. Methods Human osteoblast-like cells were seeded on porous granules of tricalcium phosphate and incubated in osteogenic media while exposed to mechanical stimulation by vibration in the infrasonic range of frequencies. The generated tissue was examined microscopically following haematoxylin eosin, trichrome and immunohistochemical staining. Results Following 14 days of incubation the generated tissue showed histological characteristics of bone-like material due to the characteristic eosinophilic staining, a positive staining for collagen trichrome and a positive specific staining for osteocalcin and collagen 1. Macroscopically, this tissue appeared in aggregates of between 0.5 cm and 2 cm. Conclusions We present evidence that the interaction of the cellular, inorganic and mechanical components in vitro can rapidly generate three-dimensional bone-like tissue that might be used as an autologous bone graft. PMID:23610651

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

    PubMed

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

    2009-10-01

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

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

    PubMed

    Wei, Xuelei; Dong, Fuhui

    2011-12-01

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

  3. Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo.

    PubMed

    Kim, Ju-Ang; Lim, Jiwon; Naren, Raja; Yun, Hui-Suk; Park, Eui Kyun

    2016-10-15

    Similar to calcium phosphates, magnesium phosphate (MgP) ceramics have been shown to be biocompatible and support favorable conditions for bone cells. Micropores below 25μm (MgP25), between 25 and 53μm (MgP53), or no micropores (MgP0) were introduced into MgP scaffolds using different sizes of an NaCl template. The porosities of MgP25 and MgP53 were found to be higher than that of MgP0 because of their micro-sized pores. Both in vitro and in vivo analysis showed that MgP scaffolds with high porosity promoted rapid biodegradation. Implantation of the MgP0, MgP25, and MgP53 scaffolds into rabbit calvarial defects (with 4- and 6-mm diameters) was assessed at two times points (4 and 8weeks), followed by analysis of bone regeneration. The micro-CT and histologic analyses of the 4-mm defect showed that the MgP25 and MgP53 scaffolds were degraded completely at 4weeks with simultaneous bone and marrow-like structure regeneration. For the 6-mm defect, a similar pattern of regeneration was observed. These results indicate that the rate of degradation is associated with bone regeneration. The MgP25 and MgP53 scaffold-implanted bone showed a better lamellar structure and enhanced calcification compared to the MgP0 scaffold because of their porosity and degradation rate. Tartrate-resistant acid phosphatase (TRAP) staining indicated that the newly formed bone was undergoing maturation and remodeling. Overall, these data suggest that the pore architecture of MgP ceramic scaffolds greatly influence bone formation and remodeling activities and thus should be considered in the design of new scaffolds for long-term bone tissue regeneration. The pore structural conditions of scaffold, including porosity, pore size, pore morphology, and pore interconnectivity affect cell ingrowth, mechanical properties and biodegradabilities, which are key components of scaffold in bone tissue regeneration. In this study, we designed hierarchical pore structure of the magnesium phosphate (Mg

  4. 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

  5. Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

    DTIC Science & Technology

    2013-01-01

    Praetorius, F. Guided tissue regeneration using de- gradable and nondegradable membranes in rabbit tibia. Clin Oral Implants Res 4, 172, 1993. 8. Queiroz... Regeneration of periodontal tissues : combinations of barrier membranes and grafting materials–biological foundation and preclinical evi- dence: a...structural graft provides benefits for bone tissue regeneration in terms of early interfacial integration. Introduction The treatment of large-bone defects

  6. 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.

  7. 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.

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

    PubMed

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

    2014-11-01

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

  9. 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.

  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. 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

  12. Cryopreservation of tissue engineered constructs for bone.

    PubMed

    Kofron, Michelle D; Opsitnick, Natalie C; Attawia, Mohamed A; Laurencin, Cato T

    2003-11-01

    The large-scale clinical use of tissue engineered constructs will require provisions for its mass availability and accessibility. Therefore, it is imperative to understand the effects of low temperature (-196 degrees C) on the tissue engineered biological system. Initial studies used samples of the osteoblast-like cell line (SaOS-2) adhered to a two-dimensional poly(lactide-co-glycolide) thin film (2D-PLAGA) or a three-dimensional poly(lactide-co-glycolide) sintered microsphere matrix (3D-PLAGA) designed for bone tissue engineering. Experimental samples were tested for their ability to maintain cell viability, following low temperature banking for one week, in solutions of the penetrating cryoprotective agents, dimethylsulfoxide (DMSO), ethylene glycol, and glycerol. Results indicated the DMSO solution yielded the greatest percent cell survival for SaOS-2 cells adhered to both the 2D- and 3D-PLAGA scaffolds; therefore, DMSO was used to cryopreserve mineralizing primary rabbit osteoblasts cells adhered to 2D-PLAGA matrices for 35 days. Results indicated retention of the extracellular matrix architecture as no statistically significant difference in the pre- and post-thaw mineralized structures was measured. Percent cell viability of the mineralized constructs following low temperature storage was approximately 50%. These are the first studies to address the issue of preservation techniques for tissue engineered constructs. The ability to successfully cryopreserve mineralized tissue engineered matrices for bone may offer an unlimited and readily available source of bone-like materials for orthopaedic applications.

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

    PubMed

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

    2011-03-01

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

  14. Avoiding Complications in Bone and Soft Tissue Ablation

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

    Kurup, A. Nicholas, E-mail: kurup.anil@mayo.edu; Schmit, Grant D., E-mail: schmit.grant@mayo.edu; Morris, Jonathan M., E-mail: morris.jonathan@mayo.edu

    As with percutaneous ablation of tumors in the liver, lungs, and kidneys, ablation of bone and non-visceral soft tissue tumors carries risk, primarily from collateral damage to vital structures in proximity to the target tumor. Certain risks are of particular interest when ablating bone and non-visceral soft tissue tumors, namely neural or skin injury, bowel injury, fracture, and gas embolism from damaged applicators. Ablation of large volume tumors also carries special risk. Many techniques may be employed by the interventional radiologist to minimize complications when treating tumors in the musculoskeletal system. These methods include those to depict, displace, or monitormore » critical structures. Thus, measures to provide thermoprotection may be active, such as careful ablation applicator placement and use of various displacement techniques, as well as passive, including employment of direct temperature, radiographic, or neurophysiologic monitoring techniques. Cementoplasty should be considered in certain skeletal locations at risk of fracture. Patients treated with large volume tumors should be monitored for renal dysfunction and properly hydrated. Finally, ablation applicators should be cautiously placed in the constrained environment of intact bone.« less

  15. 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.

  16. 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

  17. [Comparative study on graft of autogeneic iliac bone and tissue engineered bone].

    PubMed

    Shen, Bing; Xie, Fu-lin; Xie, Qing-fang

    2002-11-01

    To compare the clinical results of repairing bone defect of limbs with tissue engineering technique and with autogeneic iliac bone graft. From July 1999 to September 2001, 52 cases of bone fracture were randomly divided into two groups (group A and B). Open reduction and internal fixation were performed in all cases as routine operation technique. Autogeneic iliac bone was implanted in group A, while tissue engineered bone was implanted in group B. Routine postoperative treatment in orthopedic surgery was taken. The operation time, bleeding volume, wound healing and drainage volume were compared. The bone union was observed by the X-ray 1, 2, 3, and 5 months after operation. The sex, age and disease type had no obvious difference between groups A and B. all the wounds healed with first intention. The swelling degree of wound and drainage volume had no obvious difference. The operation time in group A was longer than that in group B (25 minutes on average) and bleeding volume in group A was larger than that in group B (150 ml on average). Bone union completed within 3 to 7 months in both groups. But there were 2 cases of delayed union in group A and 1 case in group B. Repair of bone defect with tissue engineered bone has as good clinical results as that with autogeneic iliac bone graft. In aspect of operation time and bleeding volume, tissue engineered bone graft is superior to autogeneic iliac bone.

  18. Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

    PubMed Central

    Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

    2017-01-01

    Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

  19. 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.

  20. 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. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Electromechanical Properties of Bone Tissue.

    NASA Astrophysics Data System (ADS)

    Regimbal, Raymond L.

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

  2. Nanomechanical properties of hybrid coatings for bone tissue engineering.

    PubMed

    Skarmoutsou, Amalia; Lolas, Georgios; Charitidis, Costas A; Chatzinikolaidou, Maria; Vamvakaki, Maria; Farsari, Maria

    2013-09-01

    Bone tissue engineering has emerged as a promising alternative approach in the treatment of bone injuries and defects arising from malformation, osteoporosis, and tumours. In this approach, a temporary scaffold possessing mechanical properties resembling those of natural bone is needed to serve as a substrate enhancing cell adhesion and growth, and a physical support to guide the formation of the new bone. In this regard, the scaffold should be biocompatible, biodegradable, malleable and mechanically strong. Herein, we investigate the mechanical properties of three coatings of different chemical compositions onto silanized glass substrates; a hybrid material consisting of methacryloxypropyl trimethoxysilane and zirconium propoxide, a type of a hybrid organic-inorganic material of the above containing also 50 mol% 2-(dimethylamino)ethyl methacrylate (DMAEMA) moieties and a pure organic material, based on PDMAEMA. This study investigates the variations in the measured hardness and reduced modulus values, wear resistance and plastic behaviour before and after samples' submersion in cell culture medium. Through this analysis we aim to explain how hybrid materials behave under applied stresses (pile-up formations), how water uptake changes this behaviour, and estimate how these materials will react while interaction with cells in tissue engineering applications. Finally, we report on the pre-osteoblastic cell adhesion and proliferation on three-dimensional structures of the hybrid materials within the first hour and up to 7 days in culture. It was evident that hybrid structure, consisting of 50 mol% organic-inorganic material, reveals good mechanical behaviour, wear resistance and cell adhesion and proliferation, suggesting a possible candidate in bone tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. 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

  4. Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping.

    PubMed

    Kozielski, M; Buchwald, T; Szybowicz, M; Błaszczak, Z; Piotrowski, A; Ciesielczyk, B

    2011-07-01

    Biomechanical properties of bone depend on the composition and organization of collagen fibers. In this study, Raman microspectroscopy was employed to determine the content of mineral and organic constituents and orientation of collagen fibers in spongy bone in the human head of femur at the microstructural level. Changes in composition and structure of trabecula were illustrated using Raman spectral mapping. The polarized Raman spectra permit separate analysis of local variations in orientation and composition. The ratios of ν₂PO₄³⁻/Amide III, ν₄PO₄³⁻/Amide III and ν₁CO₃²⁻/ν₂PO₄³⁻ are used to describe relative amounts of spongy bone components. The ν₁PO₄³⁻/Amide I ratio is quite susceptible to orientation effect and brings information on collagen fibers orientation. The results presented illustrate the versatility of the Raman method in the study of bone tissue. The study permits better understanding of bone physiology and evaluation of the biomechanical properties of bone.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Recent advances in gene-enhanced bone tissue engineering.

    PubMed

    Betz, Volker M; Kochanek, Stefan; Rammelt, Stefan; Müller, Peter E; Betz, Oliver B; Messmer, Carolin

    2018-03-30

    The loss of bone tissue represents a critical clinical condition that is frequently faced by surgeons. Substantial progress has been made in the area of bone research, providing insight into the biology of bone under physiological and pathological conditions, as well as tools for the stimulation of bone regeneration. The present review discusses recent advances in the field of gene-enhanced bone tissue engineering. Gene transfer strategies have emerged as highly effective tissue engineering approaches for supporting the repair of the musculoskeletal system. By contrast to treatment with recombinant proteins, genetically engineered cells can release growth factors at the site of injury over extended periods of time. Of particular interest are the expedited technologies that can be applied during a single surgical procedure in a cost-effective manner, allowing translation from bench to bedside. Several promising methods based on the intra-operative genetic manipulation of autologous cells or tissue fragments have been developed in preclinical studies. Moreover, gene therapy for bone regeneration has entered the clinical stage with clinical trials for the repair of alveolar bone. Current trends in gene-enhanced bone engineering are also discussed with respect to the movement of the field towards expedited, translational approaches. It is possible that gene-enhanced bone tissue engineering will become a clinical reality within the next few years. Copyright © 2018 John Wiley & Sons, Ltd.

  11. Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An Overview

    PubMed Central

    2011-01-01

    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. PMID:21902614

  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. Polyurethane foam/nano hydroxyapatite composite as a suitable scaffold for bone tissue regeneration.

    PubMed

    Meskinfam, M; Bertoldi, S; Albanese, N; Cerri, A; Tanzi, M C; Imani, R; Baheiraei, N; Farokhi, M; Farè, S

    2018-01-01

    In bone tissue regeneration, the use of biomineralized scaffolds to create the 3D porous structure needed for well-fitting with defect size and appropriate cell interactions, is a promising alternative to autologous and heterologous bone grafts. Biomineralized polyurethane (PU) foams are here investigated as scaffold for bone tissue regeneration. Biomineralization of the foams was carried out by activation of PU surface by a two steps procedure performed for different times (1 to 4 weeks). Scaffolds were investigated for morphological, chemico-physical and mechanical properties, as well as for in vitro interaction with rat Bone Marrow Mesenchymal Stem Cells (BMSCs). Untreated and biomineralized PU samples showed a homogenous morphology and regular pore size (average Ø=407μm). Phase and structure of formed calcium phosphates (CaPs) layer onto the PU foam were analyzed by Fourier Transform Infrared spectroscopy and X-ray diffraction, proving the formation of bone-like nano hydroxyapatite. Biomineralization caused a significant increase of mechanical properties of treated foams compared to untreated ones. Biomineralization also affected the PU scaffold cytocompatibility providing a more appropriate surface for cell attachment and proliferation. Considering the obtained results, the proposed scaffold can be considered suitable for bone tissue regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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

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

    PubMed Central

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

    2016-01-01

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

  16. 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

  17. 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

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

    PubMed

    Chinsamy, Anusuya; Tumarkin-Deratzian, Allison

    2009-09-01

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

  20. The rocker bone: a new kind of mineralised tissue?

    PubMed

    Parmentier, E; Compère, P; Casadevall, M; Fontenelle, N; Cloots, R; Henrist, C

    2008-10-01

    In some Ophidiiform fishes, the anterior part of the swimbladder is thickened into a hard structure called the "rocker bone", which is thought to play a role in sound production. Although this structure has been described as cartilage or bone, its nature is still unknown. We have made a thorough analysis of the rocker bone in Ophidion barbatum and compared it with both classical bone and cartilage. The rocker bone appears to be a new example of mineralisation. It consists of (1) a ground substance mainly composed of proteoglycans (mucopolysaccharide acid) and fibres and (2) a matrix containing small mineralised spherules composed of a bioapatite and fibrils. These spherules are embedded in mineralised cement of a similar composition to the spherules themselves. The rocker bone grows via the apposition of new apatite spherules at its periphery. These spherules are first secreted by the innermost fibroblast layer of the capsule contained in the rocker bone and then grow extracellularly. Blood vessels, which represent the only means of transport for matrix and mineral material, are numerous. They enter the rocker bone via the hyle and ramify towards the capsule. We propose to call this new kind of mineralised tissue constituting the rocker bone "frigolite" (the Belgian name for styrofoam) in reference to the presence of spherules of different sizes and the peculiarity of the rocker bone in presenting a smooth surface when fractured.

  1. 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.

  2. 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

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

    PubMed

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

    2017-09-01

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

  4. Bone Marrow Adipose Tissue and Skeletal Health.

    PubMed

    Muruganandan, Shanmugam; Govindarajan, Rajgopal; Sinal, Christopher J

    2018-05-31

    To summarize and discuss recent progress and novel signaling mechanisms relevant to bone marrow adipocyte formation and its physiological/pathophysiological implications for bone remodeling. Skeletal remodeling is a coordinated process entailing removal of old bone and formation of new bone. Several bone loss disorders such as osteoporosis are commonly associated with increased bone marrow adipose tissue. Experimental and clinical evidence supports that a reduction in osteoblastogenesis from mesenchymal stem cells at the expense of adipogenesis, as well as the deleterious effects of adipocyte-derived signaling, contributes to the etiology of osteoporosis as well as bone loss associated with aging, diabetes mellitus, post-menopause, and chronic drug therapy. However, this view is challenged by findings indicating that, in some contexts, bone marrow adipose tissue may have a beneficial impact on skeletal health. Further research is needed to better define the role of marrow adipocytes in bone physiology/pathophysiology and to determine the therapeutic potential of manipulating mesenchymal stem cell differentiation.

  5. Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

    PubMed Central

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

    2008-01-01

    Abstract Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs. PMID:18657028

  6. Microcomputed tomography characterization of neovascularization in bone tissue engineering applications.

    PubMed

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

    2008-09-01

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

  7. 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.

  8. 3D printed porous ceramic scaffolds for bone tissue engineering: a review.

    PubMed

    Wen, Yu; Xun, Sun; Haoye, Meng; Baichuan, Sun; Peng, Chen; Xuejian, Liu; Kaihong, Zhang; Xuan, Yang; Jiang, Peng; Shibi, Lu

    2017-08-22

    This study summarizes the recent research status and development of three-dimensional (3D)-printed porous ceramic scaffolds in bone tissue engineering. Recent literature on 3D-printed porous ceramic scaffolds was reviewed. Compared with traditional processing and manufacturing technologies, 3D-printed porous ceramic scaffolds have obvious advantages, such as enhancement of the controllability of the structure or improvement of the production efficiency. More sophisticated scaffolds were fabricated by 3D printing technology. 3D printed bioceramics have broad application prospects in bone tissue engineering. Through understanding the advantages and limitations of different 3D-printing approaches, new classes of bone graft substitutes can be developed.

  9. [Mechanical strength and mechano-compatibility of tissue-engineered bones].

    PubMed

    Tanaka, Shigeo

    2016-01-01

    Current artificial bones made of metals and ceramics may be replaced around a decade after implantation due to its low durability, which is brought on by a large difference from the host bone in mechanical properties, i.e., low mechano-compatibility. On the other hand, tissue engineering could be a solution with regeneration of bone tissues from stem cells in vitro. However, there are still some problems to realize exactly the same mechanical properties as those of real bone. This paper introduces the technical background of bone tissue engineering and discusses possible methods for installation of mechano-compatibility into a regenerative bone. At the end, future directions toward the realization of ideal mechano-compatible regenerative bone are proposed.

  10. 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.

  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. 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.

  13. Bone Tissue Engineering: Past-Present-Future.

    PubMed

    Quarto, Rodolfo; Giannoni, Paolo

    2016-01-01

    Bone is one of the few tissues to display a true potential for regeneration. Fracture healing is an obvious example where regeneration occurs through tightly regulated sequences of molecular and cellular events which recapitulate tissue formation seen during embryogenesis. Still in some instances, bone regeneration does not occur properly (i.e. critical size lesions) and an appropriate therapeutic intervention is necessary. Successful replacement of bone by tissue engineering will likely depend on the recapitulation of this flow of events. In fact, bone regeneration requires cross-talk between microenvironmental factors and cells; for example, resident mesenchymal progenitors are recruited and properly guided by soluble and insoluble signaling molecules. Tissue engineering attempts to reproduce and to mimic this natural milieu by delivering cells capable of differentiating into osteoblasts, inducing growth factors and biomaterials to support cellular attachment, proliferation, migration, and matrix deposition. In the last two decades, a significant effort has been made by the scientific community in the development of methods and protocols to repair and regenerate tissues such as bone, cartilage, tendons, and ligaments. In this same period, great advancements have been achieved in the biology of stem cells and on the mechanisms governing "stemness". Unfortunately, after two decades, effective clinical translation does not exist, besides a few limited examples. Many years have passed since cell-based regenerative therapies were first described as "promising approaches", but this definition still engulfs the present literature. Failure to envisage translational cell therapy applications in routine medical practice evidences the existence of unresolved scientific and technical struggles, some of which still puzzle researchers in the field and are presented in this chapter.

  14. 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. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  15. A mechano-biological model of multi-tissue evolution in bone

    NASA Astrophysics Data System (ADS)

    Frame, Jamie; Rohan, Pierre-Yves; Corté, Laurent; Allena, Rachele

    2017-12-01

    Successfully simulating tissue evolution in bone is of significant importance in predicting various biological processes such as bone remodeling, fracture healing and osseointegration of implants. Each of these processes involves in different ways the permanent or transient formation of different tissue types, namely bone, cartilage and fibrous tissues. The tissue evolution in specific circumstances such as bone remodeling and fracturing healing is currently able to be modeled. Nevertheless, it remains challenging to predict which tissue types and organization can develop without any a priori assumptions. In particular, the role of mechano-biological coupling in this selective tissue evolution has not been clearly elucidated. In this work, a multi-tissue model has been created which simultaneously describes the evolution of bone, cartilage and fibrous tissues. The coupling of the biological and mechanical factors involved in tissue formation has been modeled by defining two different tissue states: an immature state corresponding to the early stages of tissue growth and representing cell clusters in a weakly neo-formed Extra Cellular Matrix (ECM), and a mature state corresponding to well-formed connective tissues. This has allowed for the cellular processes of migration, proliferation and apoptosis to be described simultaneously with the changing ECM properties through strain driven diffusion, growth, maturation and resorption terms. A series of finite element simulations were carried out on idealized cantilever bending geometries. Starting from a tissue composition replicating a mid-diaphysis section of a long bone, a steady-state tissue formation was reached over a statically loaded period of 10,000 h (60 weeks). The results demonstrated that bone formation occurred in regions which are optimally physiologically strained. In two additional 1000 h bending simulations both cartilaginous and fibrous tissues were shown to form under specific geometrical and loading

  16. 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.

  17. 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

  18. Biofabrication of soft tissue templates for engineering the bone-ligament interface.

    PubMed

    Harris, Ella; Liu, Yurong; Cunniffe, Grainne; Morrissey, David; Carroll, Simon; Mulhall, Kevin; Kelly, Daniel J

    2017-10-01

    Regenerating damaged tissue interfaces remains a significant clinical challenge, requiring recapitulation of the structure, composition, and function of the native enthesis. In the ligament-to-bone interface, this region transitions from ligament to fibrocartilage, to calcified cartilage and then to bone. This gradation in tissue types facilitates the transfer of load between soft and hard structures while minimizing stress concentrations at the interface. Previous attempts to engineer the ligament-bone interface have utilized various scaffold materials with an array of various cell types and/or biological cues. The primary goal of this study was to engineer a multiphased construct mimicking the ligament-bone interface by driving differentiation of a single population of mesenchymal stem cells (MSCs), seeded within blended fibrin-alginate hydrogels, down an endochondral, fibrocartilaginous, or ligamentous pathway through spatial presentation of growth factors along the length of the construct within a custom-developed, dual-chamber culture system. MSCs within these engineered constructs demonstrated spatially distinct regions of differentiation, adopting either a cartilaginous or ligamentous phenotype depending on their local environment. Furthermore, there was also evidence of spatially defined progression toward an endochondral phenotype when chondrogenically primed MSCs within this construct were additionally exposed to hypertrophic cues. The study demonstrates the feasibility of engineering spatially complex soft tissues within a single MSC laden hydrogel through the defined presentation of biochemical cues. This novel approach represents a new strategy for engineering the ligament-bone interface. Biotechnol. Bioeng. 2017;114: 2400-2411. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. 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

  20. 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.

  1. [Experimental-morphologic study of bone tissue reaction to carbon-containing material implantation with initiated X-ray contrast property].

    PubMed

    Grigorian, A S; Nabiev, F Kh; Golovin, R V

    2005-01-01

    In experimental study on 15 rabbits (chinchilla) influence of titanium plates implanted lapped on adjacent tissues in the region of the lower jaw body (comparison group) and carbon material with added boron in the concentrations of 8 and 15% (the study group) was studied. Results of the experimental-morphological investigation show that carbon-based materials with boron addition (with its content 8 and 15%) did not impede adaptive rebuilding of bone tissues and in particular bone structure regeneration in the process of reactive rebuilding of the "maternal" bone. Moreover, as the result of reactive processes developing in osseous tissues after implantation of the tested materials their successful integration in surrounding tissue structures was detected.

  2. 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. © 2016 Wiley Periodicals, Inc.

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

    PubMed

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

    2016-01-01

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

  4. Bone Tissue Donation: Tendency and Hurdles.

    PubMed

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

    2018-03-01

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

  5. 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.

  6. 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

    2017-11-01

    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

  7. 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

  8. 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

  9. [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.

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

    PubMed

    Ruggiu, Alessandra; Cancedda, Ranieri

    2015-12-01

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

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

    PubMed

    Ohgushi, Hajime

    2014-10-01

    Osteo/chondrogenic differentiation capabilities are seen after in vivo implantation of mesenchymal stem cells (MSCs), which are currently used for the patients having bone/cartilage defects. Importantly, the differentiation capabilities are induced by culturing technology, resulting in in vitro bone/cartilage formation. Especially, the in vitro bone tissue is useful for bone tissue regeneration. For cartilage regeneration, culture expanded chondrocytes derived from patient's normal cartilage are also used for the patients having cartilage damages. Recently, the cultured chondrocytes embedded in atelocollagen gel are obtainable as tissue engineered products distributed by Japan Tissue Engineering Co. Ltd. The products are available in the well-regulated hospitals by qualified orthopedic surgeons. The criteria for these hospitals/surgeons have been established. This review paper focuses on current status of bone/cartilage tissue engineering towards clinical applications in Japan.

  12. Animal models for bone tissue engineering and modelling disease

    PubMed Central

    Griffin, Michelle

    2018-01-01

    ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

  13. 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

  14. The Metabolic Microenvironment Steers Bone Tissue Regeneration.

    PubMed

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

    2018-02-01

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

  15. 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

  16. 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. Published by Elsevier Inc.

  17. Multimodal correlative investigation of the interplaying micro-architecture, chemical composition and mechanical properties of human cortical bone tissue reveals predominant role of fibrillar organization in determining microelastic tissue properties.

    PubMed

    Schrof, Susanne; Varga, Peter; Hesse, Bernhard; Schöne, Martin; Schütz, Roman; Masic, Admir; Raum, Kay

    2016-10-15

    The mechanical competence of bone is crucially determined by its material composition and structural design. To investigate the interaction of the complex hierarchical architecture, the chemical composition and the resulting elastic properties of healthy femoral bone at the level of single bone lamellae and entire structural units, we combined polarized Raman spectroscopy (PRS), scanning acoustic microscopy (SAM) and synchrotron X-ray phase contrast nano tomography (SR-nanoCT). In line with earlier studies, mutual correlation analysis strongly suggested that the characteristic elastic modulations of bone lamellae within single units are the result of the twisting fibrillar orientation, rather than compositional variations, modulations of the mineral particle maturity, or mass density deviations. Furthermore, we show that predominant fibril orientations in entire tissue units can be rapidly assessed from Raman parameter maps. Coexisting twisted and oscillating fibril patterns were observed in all investigated tissue domains. Ultimately, our findings demonstrate in particular the potential of combined PRS and SAM measurements in providing multi-scalar analysis of correlated fundamental tissue properties. In future studies, the presented approach can be applied for non-destructive investigation of small pathologic samples from bone biopsies and a broad range of biological materials and tissues. Bone is a complex structured composite material consisting of collagen fibrils and mineral particles. Various studies have shown that not only composition, maturation, and packing of its components, but also their structural arrangement determine the mechanical performance of the tissue. However, prominent methodologies are usually not able to concurrently describe these factors on the micron scale and complementary tissue characterization remains challenging. In this study we combine X-ray nanoCT, polarized Raman imaging and scanning acoustic microscopy and propose a protocol

  18. 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.

  19. 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

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

    PubMed

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

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

  1. 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

  2. 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 (GelMA LOW ) 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.

  3. 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

  4. Characterization of bone tissue using microstrip antennas.

    PubMed

    Barros, Jannayna D; de Oliveira, Jose Josemar; da Silva, Sandro G

    2010-01-01

    The use of electromagnetic waves in the characterization of biological tissues has been conducted since the nineteenth century after the confirmation that electric and magnetic fields can interact with biological materials. In this paper, electromagnetic waves are used to characterize tissues with different levels of bone mass. In this way, one antenna array on microstrip lines was used. It can be seen that bones with different mass has different behavior in microwave frequencies.

  5. An overview on autologous fibrin glue in bone tissue engineering of maxillofacial surgery

    PubMed Central

    Khodakaram-Tafti, Azizollah; Mehrabani, Davood; Shaterzadeh-Yazdi, Hanieh

    2017-01-01

    The purpose of this review is to have an overview on the applications on the autologous fibrin glue as a bone graft substitute in maxillofacial injuries and defects. A search was conducted using the databases such as Medline or PubMed and Google Scholar for articles from 1985 to 2016. The criteria were “Autograft,” “Fibrin tissue adhesive,” “Tissue engineering,” “Maxillofacial injury,” and “Regenerative medicine.” Bone tissue engineering is a new promising approach for bone defect reconstruction. In this technique, cells are combined with three-dimensional scaffolds to provide a tissue-like structure to replace lost parts of the tissue. Fibrin as a natural scaffold, because of its biocompatibility and biodegradability, and the initial stability of the grafted stem cells is introduced as an excellent scaffold for tissue engineering. It promotes cell migration, proliferation, and matrix making through acceleration in angiogenesis. Growth factors in fibrin glue can stimulate and promote tissue repair. Autologous fibrin scaffolds are excellent candidates for tissue engineering so that they can be produced faster, cheaper, and in larger quantities. In addition, they are easy to use and the probability of viral or prion transmission may be decreased. Therefore, autologous fibrin glue appears to be promising scaffold in regenerative maxillofacial surgery. PMID:28584530

  6. 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

  7. Bone tissue engineering: state of the art and future trends.

    PubMed

    Salgado, António J; Coutinho, Olga P; Reis, Rui L

    2004-08-09

    Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds processed by using a methodology based on extrusion with blowing agents.

  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. 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

  10. Comparative studies on bone structure in dairy cows with different feeding conditions.

    PubMed

    Pilmane, M; Zitare, I; Jemeljanovs, A

    2010-01-01

    The bone belongs to the dynamic tissues and its structure in domestic cows is still not completely understood in correlation to the impact of different food components. The aim of our work was a histomorphometrical and immunohistochemical research on bone morphology and factors influencing it in healthy dairy cows fed with self-produced grain and with rapeseed cakes. The bone of self-produced grain-fed cows demonstrated statistically significant difference in the number of osteocytes from the bone of rapeseed cakes-fed cows. The rapeseed cakes-fed cows didn't show any bone cell positive for BMP2/4, while FGFR1 increased significantly in their supportive tissues. The number of bFGF- and apoptosis-containing structures varied in cows of both groups. MMP2 expression showed statistically significant difference between both animals' groups with domination in bone of cows fed with self-produced grain. Defensin-, osteopontin- and osteocalcin-containing cells showed tendency to increase in bone of cows on rapeseed cakes diet. Conclusions. The rapeseed-fed cow's long bones demonstrate significant decrease of osteocytes per mm2 and selective increase of FGFR1, suggesting the (compensatory) growth stimulation in supportive tissue. The statistically significant selective absence of MMP2 with a slight tendency of increase in osteopontin and osteocalcin in rapeseed-fed cow's long bones indicates the persistence of seemingly still compensated qualitative changes in bone (beginning of disturbances in mineralization, metabolism etc.) proved also by a slight increase of the bone antimicrobial peptide.

  11. A short review: Recent advances in electrospinning for bone tissue regeneration

    PubMed Central

    Shin, Song-Hee; Purevdorj, Odnoo; Castano, Oscar; Planell, Josep A

    2012-01-01

    Nanofibrous structures developed by electrospinning technology provide attractive extracellular matrix conditions for the anchorage, migration, and differentiation of tissue cells, including those responsible for the regeneration of hard tissues. Together with the ease of set up and cost-effectiveness, the possibility to produce nanofibers with a wide range of compositions and morphologies is the merit of electrospinning. Significant efforts have exploited the development of bone regenerative nanofibers, which includes tailoring of composite/hybrid compositions that are bone mimicking and the surface functionalization such as mineralization. Moreover, by utilizing bioactive molecules such as adhesive proteins, growth factors, and chemical drugs, in concert with the nanofibrous matrices, it is possible to provide artificial materials with improved cellular responses and therapeutic efficacy. These studies have mainly focused on the regulation of stem cell behaviors for use in regenerative medicine and tissue engineering. While there are some challenges in achieving controllable delivery of bioactive molecules and complex-shaped three-dimensional scaffolds for tissue engineering, the electrospun nanofibrous matrices can still have a beneficial impact in the area of hard-tissue regeneration. PMID:22511995

  12. Regional Variation of Bone Tissue Properties at the Human Mandibular Condyle

    PubMed Central

    Kim, Do-Gyoon; Jeong, Yong-Hoon; Kosel, Erin; Agnew, Amanda M.; McComb, David W.; Bodnyk, Kyle; Hart, Richard T.; Kim, Min Kyung; Han, Sang Yeun; Johnston, William M.

    2015-01-01

    The temporomandibular joint (TMJ) bears different types of static and dynamic loading during occlusion and mastication. As such, characteristics of mandibular condylar bone tissue play an important role in determining the mechanical stability of the TMJ under the macro-level loading. Thus, the objective of this study was to examine regional variation of the elastic, plastic, and viscoelastic mechanical properties of human mandibular condylar bone tissue using nanoindentation. Cortical and trabecular bone were dissected from mandibular condyles of human cadavers (9 males, 54 to 96 years). These specimens were scanned using microcomputed tomography to obtain bone tissue mineral distribution. Then, nanoindentation was conducted on the surface of the same specimens in hydration. Plastic hardness (H) at a peak load, viscoelastic creep (Creep/Pmax), viscosity (η), and tangent delta (tan δ) during a 30 second hold period, and elastic modulus (E) during unloading were obtained by a cycle of indentation at the same site of bone tissue. The tissue mineral and nanoindentation parameters were analyzed for the periosteal and endosteal cortex, and trabecular bone regions of the mandibular condyle. The more mineralized periosteal cortex had higher mean values of elastic modulus, plastic hardness, and viscosity but lower viscoelastic creep and tan δ than the less mineralized trabecular bone of the mandibular condyle. These characteristics of bone tissue suggest that the periosteal cortex tissue may have more effective properties to resist elastic, plastic, and viscoelastic deformation under static loading, and the trabecular bone tissue to absorb and dissipate time-dependent viscoelastic loading energy at the TMJ during static occlusion and dynamic mastication. PMID:25913634

  13. Dynamic Bioreactor Culture of High Volume Engineered Bone Tissue

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-07-12

    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.

  15. 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.

  16. 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

  17. In vitro characterization of 3D printed scaffolds aimed at bone tissue regeneration.

    PubMed

    Boga, João C; Miguel, Sónia P; de Melo-Diogo, Duarte; Mendonça, António G; Louro, Ricardo O; Correia, Ilídio J

    2018-05-01

    The incidence of fractures and bone-related diseases like osteoporosis has been increasing due to aging of the world's population. Up to now, grafts and titanium implants have been the principal therapeutic approaches used for bone repair/regeneration. However, these types of treatment have several shortcomings, like limited availability, risk of donor-to-recipient infection and tissue morbidity. To overcome these handicaps, new 3D templates, capable of replicating the features of the native tissue, are currently being developed by researchers from the area of tissue engineering. These 3D constructs are able to provide a temporary matrix on which host cells can adhere, proliferate and differentiate. Herein, 3D cylindrical scaffolds were designed to mimic the natural architecture of hollow bones, and to allow nutrient exchange and bone neovascularization. 3D scaffolds were produced with tricalcium phosphate (TCP)/alginic acid (AA) using a Fab@home 3D printer. Furthermore, graphene oxide (GO) was incorporated into the structure of some scaffolds to further enhance their mechanical properties. The results revealed that the scaffolds incorporating GO displayed greater porosity, without impairing their mechanical properties. These scaffolds also presented a controlled swelling profile, enhanced biomineralization capacity and were able to increase the Alkaline Phosphatase (ALP) activity. Such characteristics make TCP/AA scaffolds functionalized with GO promising 3D constructs for bone tissue engineering applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated extracellular matrix.

    PubMed

    Jusoh, Norhana; Oh, Soojung; Kim, Sudong; Kim, Jangho; Jeon, Noo Li

    2015-10-21

    Current in vitro systems mimicking bone tissues fail to fully integrate the three-dimensional (3D) microvasculature and bone tissue microenvironments, decreasing their similarity to in vivo conditions. Here, we propose 3D microvascular networks in a hydroxyapatite (HA)-incorporated extracellular matrix (ECM) for designing and manipulating a vascularized bone tissue model in a microfluidic device. Incorporation of HA of various concentrations resulted in ECM with varying mechanical properties. Sprouting angiogenesis was affected by mechanically modulated HA-extracellular matrix interactions, generating a model of vascularized bone microenvironment. Using this platform, we observed that hydroxyapatite enhanced angiogenic properties such as sprout length, sprouting speed, sprout number, and lumen diameter. This new platform integrates fibrin ECM with the synthetic bone mineral HA to provide in vivo-like microenvironments for bone vessel sprouting.

  19. 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.

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

    PubMed

    Sethu, Sai Nievethitha; Namashivayam, Subhapradha; Devendran, Saravanan; Nagarajan, Selvamurugan; Tsai, Wei-Bor; Narashiman, Srinivasan; Ramachandran, Murugesan; Ambigapathi, 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 CaPO 4 (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. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Lu, Yanfei; Lekszycki, Tomasz

    2018-03-01

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

  2. A review of fibrin and fibrin composites for bone tissue engineering

    PubMed Central

    Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

    2017-01-01

    Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the

  3. A review of fibrin and fibrin composites for bone tissue engineering.

    PubMed

    Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

    2017-01-01

    Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the

  4. Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

    PubMed

    Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

    2013-11-01

    Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

  5. Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone.

    PubMed

    Weinand, Christian; Pomerantseva, Irina; Neville, Craig M; Gupta, Rajiv; Weinberg, Eli; Madisch, Ijad; Shapiro, Frederic; Abukawa, Harutsugi; Troulis, Maria J; Vacanti, Joseph P

    2006-04-01

    Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes; significant donor site morbidity is another major disadvantage to this approach. To overcome these limitations, we used a tissue engineering approach to create bone replacements in vitro, combining bone-marrow-derived differentiated mesenchymal stem cells (MSCs) suspended in hydrogels and 3-dimensionally printed (3DP) porous scaffolds made of beta-tricalcium-phosphate (beta-TCP). The scaffolds provided support for the formation of bone tissue in collagen I, fibrin, alginate, and pluronic F127 hydrogels during culturing in oscillating and rotating dynamic conditions. Histological evaluation including toluidine blue, alkaline phosphatase, and von Kossa staining was done at 1, 2, 4, and 6 weeks. Radiographic evaluation and high-resolution volumetric CT (VCT) scanning, expression of bone-specific genes and biomechanical compression testing were performed at 6 weeks. Both culture conditions resulted in similar bone tissue formation. Histologically collagen I and fibrin hydrogels specimens had superior bone tissue, although radiopacities were detected only in collagen I samples. VCT scan revealed density values in all but the Pluronic F127 samples, with Houndsfield unit values comparable to native bone in collagen I and fibrin glue samples. Expression of bone-specific genes was significantly higher in the collagen I samples. Pluronic F127 hydrogel did not support formation of bone tissue. All samples cultured in dynamic oscillating conditions had slightly higher mechanical strength than under rotating conditions. Bone tissue can be successfully formed in vitro using constructs comprised of collagen I hydrogel, MSCs, and porous beta-TCP scaffolds.

  6. 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

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

    PubMed

    Zerath, E

    1999-07-01

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

  8. 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.

  9. 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

  10. 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.

  11. [Forensic medical aspects of bone tissue injuries and pathology].

    PubMed

    Nagornov, M N; Osipenkova-Vichtomova, T K

    2012-01-01

    This paper reports the results of a number of investigations into forensic medical aspects of bone tissue injuries and pathology that may be of value, both theoretical and practical, for the further studies in this field. The data obtained shed light on the influence of bone porosity on the mechanism of fractures and processes of reparation in the bone tissue. Moreover, they can be used for the purpose of forensic medical expertise.

  12. 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

  13. Carbon Nanoparticle Enhance Photoacoustic Imaging and Therapy for Bone Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Talukdar, Yahfi

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

  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. 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.

  16. Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer.

    PubMed

    Gregor, Aleš; Filová, Eva; Novák, Martin; Kronek, Jakub; Chlup, Hynek; Buzgo, Matěj; Blahnová, Veronika; Lukášová, Věra; Bartoš, Martin; Nečas, Alois; Hošek, Jan

    2017-01-01

    The primary objective of Tissue engineering is a regeneration or replacement of tissues or organs damaged by disease, injury, or congenital anomalies. At present, Tissue engineering repairs damaged tissues and organs with artificial supporting structures called scaffolds. These are used for attachment and subsequent growth of appropriate cells. During the cell growth gradual biodegradation of the scaffold occurs and the final product is a new tissue with the desired shape and properties. In recent years, research workplaces are focused on developing scaffold by bio-fabrication techniques to achieve fast, precise and cheap automatic manufacturing of these structures. Most promising techniques seem to be Rapid prototyping due to its high level of precision and controlling. However, this technique is still to solve various issues before it is easily used for scaffold fabrication. In this article we tested printing of clinically applicable scaffolds with use of commercially available devices and materials. Research presented in this article is in general focused on "scaffolding" on a field of bone tissue replacement. Commercially available 3D printer and Polylactic acid were used to create originally designed and possibly suitable scaffold structures for bone tissue engineering. We tested printing of scaffolds with different geometrical structures. Based on the osteosarcoma cells proliferation experiment and mechanical testing of designed scaffold samples, it will be stated that it is likely not necessary to keep the recommended porosity of the scaffold for bone tissue replacement at about 90%, and it will also be clarified why this fact eliminates mechanical properties issue. Moreover, it is demonstrated that the size of an individual pore could be double the size of the recommended range between 0.2-0.35 mm without affecting the cell proliferation. Rapid prototyping technique based on Fused deposition modelling was used for the fabrication of designed scaffold

  17. 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.

  18. Evaluation of bone tissue response to a sealer containing mineral trioxide aggregate.

    PubMed

    Assmann, Eloísa; Böttcher, Daiana Elisabeth; Hoppe, Carolina Bender; Grecca, Fabiana Soares; Kopper, Patrícia Maria Poli

    2015-01-01

    This study analyzed bone tissue reactions to MTA Fillapex (Ângelus Industria de Produtos Odontológicos Ltda, Londrina, Brazil) compared with an epoxy resin-based material in the femur of Wistar rats. Bone tissue reactions were evaluated in 15 animals after 7, 30, and 90 days (n = 5 per period). Three surgical cavities were prepared on the femur and filled with 0.2 mL MTA Fillapex, AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany), or no sealer (negative control). By the end of each experimental period, 5 animals were randomly euthanized. The samples were histologically processed and analyzed using a light microscope. The presence of inflammatory cells, fibers, and hard tissue barrier formation was evaluated. Differences among the groups and between the 3 experimental periods were evaluated by using 2-way analysis of variance followed by the Bonferroni post hoc test (P ≤ .05). MTA Fillapex scored significantly higher for neutrophils at 7 days than at 90. At 7 days, the same occurred when comparing MTA Fillapex with AH Plus. The presence of lymphocytes/plasmocytes significantly decreased over time in all groups. Macrophages, giant cells, eosinophils, and fiber condensation presented no differences among groups and periods. Within 90 days, all groups presented complete hard tissue barrier formation. The presence of mineral trioxide aggregate in MTA Fillapex composition did not improve the bone tissue repair. The presence of sealers provided the re-establishment of the original bone tissue structure and the inflammatory response decreased over time, so they can be considered biocompatible. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  19. Bioactive Molecule-loaded Drug Delivery Systems to Optimize Bone Tissue Repair.

    PubMed

    Oshiro, Joao Augusto; Sato, Mariana Rillo; Scardueli, Cassio Rocha; Lopes de Oliveira, Guilherme Jose Pimentel; Abucafy, Marina Paiva; Chorilli, Marlus

    2017-01-01

    Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Osteogenically differentiated mesenchymal stem cells and ceramics for bone tissue engineering.

    PubMed

    Ohgushi, Hajime

    2014-02-01

    In the human body, cells having self-renewal and multi-differentiation capabilities reside in many tissues and are called adult stem cells. In bone marrow tissue, two types of stem cells are well known: hematopoietic stem cells and mesenchymal stem cells (MSCs). Though the number of MSCs in bone marrow tissue is very low, it can be increased by in vitro culture of the marrow, and culture-expanded MSCs are available for various tissue regeneration. The culture-expanded MSCs can further differentiate into osteogenic cells such as bone forming osteoblasts by culturing the MSCs in an osteogenic medium. This paper discusses osteogenically differentiated MSCs derived from the bone marrow of patients. Importantly, the differentiation can be achieved on ceramic surfaces which demonstrate mineralized bone matrix formation as well as appearance of osteogenic cells. The cell/matrix/ceramic constructs could show immediate in vivo bone formation and are available for bone reconstruction surgery. Currently, MSCs are clinically available for the regeneration of various tissues due to their high proliferation/differentiation capabilities. However, the capabilities are still limited and thus technologies to improve or recover the inherent capabilities of MSCs are needed.

  1. Bone tissue reactions to biomimetic ion-substituted apatite surfaces on titanium implants.

    PubMed

    Ballo, Ahmed M; Xia, Wei; Palmquist, Anders; Lindahl, Carl; Emanuelsson, Lena; Lausmaa, Jukka; Engqvist, Håkan; Thomsen, Peter

    2012-07-07

    The aim of this study was to evaluate the bone tissue response to strontium- and silicon-substituted apatite (Sr-HA and Si-HA) modified titanium (Ti) implants. Sr-HA, Si-HA and HA were grown on thermally oxidized Ti implants by a biomimetic process. Oxidized implants were used as controls. Surface properties, i.e. chemical composition, surface thickness, morphology/pore characteristics, crystal structure and roughness, were characterized with various analytical techniques. The implants were inserted in rat tibiae and block biopsies were prepared for histology, histomorphometry and scanning electron microscopy analysis. Histologically, new bone formed on all implant surfaces. The bone was deposited directly onto the Sr-HA and Si-HA implants without any intervening soft tissue. The statistical analysis showed significant higher amount of bone-implant contact (BIC) for the Si-doped HA modification (P = 0.030), whereas significant higher bone area (BA) for the Sr-doped HA modification (P = 0.034), when compared with the non-doped HA modification. The differences were most pronounced at the early time point. The healing time had a significant impact for both BA and BIC (P < 0.001). The present results show that biomimetically prepared Si-HA and Sr-HA on Ti implants provided bioactivity and promoted early bone formation.

  2. Expression profiling of microRNAs in human bone tissue from postmenopausal women.

    PubMed

    De-Ugarte, Laura; Serra-Vinardell, Jenny; Nonell, Lara; Balcells, Susana; Arnal, Magdalena; Nogues, Xavier; Mellibovsky, Leonardo; Grinberg, Daniel; Diez-Perez, Adolfo; Garcia-Giralt, Natalia

    2018-01-01

    Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one physiological condition. The aim of this study was to explore the miRNA expression profile of bone tissue from postmenopausal women. Tissue was obtained from trabecular bone and was analyzed in fresh conditions (n = 6). Primary osteoblasts were also obtained from trabecular bone (n = 4) and human osteoclasts were obtained from monocyte precursors after in vitro differentiation (n = 5). MicroRNA expression profiling was obtained for each sample by microarray and a global miRNA analysis was performed combining the data acquired in all the microarray experiments. From the 641 miRNAs detected in bone tissue samples, 346 (54%) were present in osteoblasts and/or osteoclasts. The other 46% were not identified in any of the bone cells analyzed. Intersection of osteoblast and osteoclast arrays identified 101 miRNAs shared by both cell types, which accounts for 30-40% of miRNAs detected in these cells. In osteoblasts, 266 miRNAs were detected, of which 243 (91%) were also present in the total bone array, representing 38% of all bone miRNAs. In osteoclasts, 340 miRNAs were detected, of which 196 (58%) were also present in the bone tissue array, representing 31% of all miRNAs detected in total bone. These analyses provide an overview of miRNAs expressed in bone tissue, broadening our knowledge in the microRNA field.

  3. 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.

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

    PubMed

    Abrahamsson, Peter

    2011-01-01

    Insufficient regeneration of missing bone and soft-tissue may present aesthetic or functional problems in patients indicated for dental implant surgery. Several techniques such as bone grafts, bone substitutes and guided tissue regeneration (GTR) have been described to rebuild a compromised alveolar ridge. Adequate soft-tissue coverage of grafted bone and titanium-mesh is important to avoid exposure which may result in loss of the bone graft. The general aim of this thesis was to evaluate use of an osmotic tissue expander for expanding intra-oral soft tissue--creating a surplus of soft tissue-- in preparation for onlay bone grafting. An experimental rabbit model was used in studies (I), (II) and (III). In (I) an osmotic soft-tissue expander was placed bilaterally on the lateral wall of the mandible via an extra-oral approach. After two weeks of expansion the rabbits were killed and specimens were collected for histology. No inflammatory reaction and no resorbtion of the cortical bone occured. The periosteum was expanded and new bone formation was seen in the edges of the expander. In (II) and (III) the expander was placed under the periosteum in the same way as in (I): bilaterally in 13 rabbits in (II) and unilaterally in 11 rabbits in (III). After two weeks of expansion the expander was identified and removed. In (II) particulated bone was placed at the recipient site protected by a titanium mesh in one site and a bio-resorbable mesh on the other site. In (III), DBBM particles and bone particles collected from the lateral border of the mandible separated by a collagen membrane was placed at the recipient site. The graft was protected by a pre-bent titanium mesh covered by a collagen membrane. After a healing period of 3 months specimens were collected for histological and SEM examination. New bone was growing in direct contact with the titanium mesh and bio resorbable mesh. The newly formed bone had the same calcium content as the mature bone in the base of the

  6. Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone.

    PubMed

    Ng, Angela M H; Tan, K K; Phang, M Y; Aziyati, O; Tan, G H; Isa, M R; Aminuddin, B S; Naseem, M; Fauziah, O; Ruszymah, B H I

    2008-05-01

    Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering. Copyright 2007 Wiley Periodicals, Inc.

  7. * 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.

  8. Melatonin effects on hard tissues: bone and tooth.

    PubMed

    Liu, Jie; Huang, Fang; He, Hong-Wen

    2013-05-10

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

  9. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis.

    PubMed

    De Fusco, Carolina; Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Moscatelli, Fiorenzo; Valenzano, Anna; Esposito, Teresa; Sergio, Chieffi; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    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.

  10. Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

    PubMed Central

    Samorezov, Julia E.; Alsberg, Eben

    2015-01-01

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

  11. Calcium- and Phosphorus-Supplemented Diet Increases Bone Mass after Short-Term Exercise and Increases Bone Mass and Structural Strength after Long-Term Exercise in Adult Mice

    PubMed Central

    Friedman, Michael A.; Bailey, Alyssa M.; Rondon, Matthew J.; McNerny, Erin M.; Sahar, Nadder D.; Kohn, David H.

    2016-01-01

    Exercise has long-lasting benefits to bone health that may help prevent fractures by increasing bone mass, bone strength, and tissue quality. Long-term exercise of 6–12 weeks in rodents increases bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls. Short-term exercise can, however, increase tissue strength, suggesting that exercise may create competition for minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups–exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and

  12. 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

  13. Composites structures for bone tissue reconstruction

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

    Neto, W.; Santos, João; Avérous, L.

    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 tomore » be used as scaffold for cell growth.« less

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

    PubMed

    Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

    2015-12-01

    Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-11-01

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

  16. 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

  17. 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.

  18. Mineralized alginate hydrogels using marine carbonates for bone tissue engineering applications.

    PubMed

    Diaz-Rodriguez, P; Garcia-Triñanes, P; Echezarreta López, M M; Santoveña, A; Landin, M

    2018-09-01

    The search for an ideal bone tissue replacement has led to the development of new composite materials designed to simulate the complex inorganic/organic structure of bone. The present work is focused on the development of mineralized calcium alginate hydrogels by the addition of marine derived calcium carbonate biomineral particles. Following a novel approach, we were able to obtain calcium carbonate particles of high purity and complex micro and nanostructure dependent on the source material. Three different types of alginates were selected to develop inorganic/organic scaffolds in order to correlate alginate composition with scaffold properties and cell behavior. The incorporation of calcium carbonates into alginate networks was able to promote extracellular matrix mineralization and osteoblastic differentiation of mesenchymal stem cells when added at 7 mg/ml. We demonstrated that the selection of the alginate type and calcium carbonate origin is crucial to obtain adequate systems for bone tissue engineering as they modulate the mechanical properties and cell differentiation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Development of a 3D bone marrow adipose tissue model.

    PubMed

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

    2018-01-26

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

  20. [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.

  1. Development of a biodegradable scaffold with interconnected pores by heat fusion and its application to bone tissue engineering.

    PubMed

    Shin, Michael; Abukawa, Harutsugi; Troulis, Maria J; Vacanti, Joseph P

    2008-03-01

    Tissue engineering has been proposed as an approach to alleviate the shortage of donor tissue and organs by combining cells and a biodegradable scaffold as a temporary extracellular matrix. While numerous scaffold fabrication methods have been proposed, tissue formation is typically limited to the surface of the scaffolds in bone tissue engineering applications due to early calcification on the surface. To improve tissue formation, a novel scaffold with a hierarchical interconnected pore structure on two distinct length scales has been developed. Here we present the fabrication process and the application of the scaffold to bone tissue engineering. Porous poly(lactide-co-glycolide) (PLGA) scaffolds were made by combining solvent casting/particulate leaching with heat fusion. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were differentiated into osteoblasts and cultured on these scaffolds in vitro for 2, 4, and 6 weeks. Subsequently, the constructs were assessed using histology and scanning electron microscopy. The bone marrow-derived osteoblasts attached well on these scaffolds. Cells were observed throughout the scaffolds. These initial results show promise for this scaffold to aid in the regeneration of bone. (c) 2007 Wiley Periodicals, Inc.

  2. 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.

  3. 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

  4. Polymicrobial periodontal pathogens transcriptomes in calvarial bone and soft tissue

    PubMed Central

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

    2011-01-01

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

  5. The emerging role of bone marrow adipose tissue in bone health and dysfunction.

    PubMed

    Ambrosi, Thomas H; Schulz, Tim J

    2017-12-01

    Replacement of red hematopoietic bone marrow with yellow adipocyte-rich marrow is a conserved physiological process among mammals. The extent of this conversion is influenced by a wide array of pathological and non-pathological conditions. Of particular interest is the observation that some marrow adipocyte-inducing factors seem to oppose each other, for instance obesity and caloric restriction. Intriguingly, several important molecular characteristics of bone marrow adipose tissue (BMAT) are distinct from the classical depots of white and brown fat tissue. This depot of fat has recently emerged as an active part of the bone marrow niche that exerts paracrine and endocrine functions thereby controlling osteogenesis and hematopoiesis. While some functions of BMAT may be beneficial for metabolic adaptation and bone homeostasis, respectively, most findings assign bone fat a detrimental role during regenerative processes, such as hematopoiesis and osteogenesis. Thus, an improved understanding of the biological mechanisms leading to formation of BMAT, its molecular characteristics, and its physiological role in the bone marrow niche is warranted. Here we review the current understanding of BMAT biology and its potential implications for health and the development of pathological conditions.

  6. 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.

  7. 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.

  8. 3D bioactive composite scaffolds for bone tissue engineering.

    PubMed

    Turnbull, Gareth; Clarke, Jon; Picard, Frédéric; Riches, Philip; Jia, Luanluan; Han, Fengxuan; Li, Bin; Shu, Wenmiao

    2018-09-01

    Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed.

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

    NASA Astrophysics Data System (ADS)

    Duer, Melinda J.

    2015-04-01

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

  10. 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

  11. 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.

  12. [An experimental study on the implantation of a biomaterial with electro-activity for replacement of hard tissue in bone].

    PubMed

    Chen, L; Chen, Z; Zhang, M

    2001-12-01

    To assess the effects of a piezoelectric biological ceramic on osteogenesis. Hydroxyapatite (HA) and piezoelectric biological ceramics (hydroxyapatite and barium titanate, HABT) were implanted in the jawbones of 5 dogs, and for sample collection, the dogs were killed separately at 1 week, 2 weeks, 1 month, 2 months and 3 months after implantation. The samples from a rhesus monkey and a blank control were collected 34 months after implantation. The implanted samples and surrounding tissues were subjected to histological observations using light microscopy (LM) and scanning electronmicroscopy (SEM) were made. Compared with the control groups, the HABTs promoted osteogenesis significantly. One week after implantation, new bone tissues were found on the surface vertical to the longitudinal direction of HABT; more bone tissues were found after 2 weeks. HABTs induced the bone tissues to arrange orderly. After two years and ten months of implantation, the piezoelectric bioceramic and bone became monolithic, and the structure of bone was normal. HABTs could promote osteogenesis.

  13. Design variables for mechanical properties of bone tissue scaffolds.

    PubMed

    Howk, Daniel; Chu, Tien-Min G

    2006-01-01

    The reconstruction of segmental defect in long bone is a clinical challenge. Multiple surgeries are typically required to restore the structure and function of the affected defect site. In order to overcome this defect a biodegradable bone tissue engineering scaffold is used. This scaffold acts as a carrier of proteins and growth factors, while also supporting the load that the bone would normally sustain, until the natural bone can regenerate in its place. Work was done to optimize an existing solid free-form scaffold design. The goal of the optimization was to increase the porosity of the scaffold while maintaining the strength of a previously-tested prototype design. With this in mind, eight new designs were created. These designs were drawn using CAD software and then through the use of finite element analysis the theoretical ultimate compressive strength of each design was obtained. Each scaffold design was constructed by casting a thermal-curable poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) suspension into wax molds fabricated on inkjet printing rapid prototyping machine. The constructs were then experimentally tested by applying a uniaxial compressive load. The theoretical and experimental values of ultimate compressive strength and specific strength of each design were compared. Theoretically, the best scaffold design produced from this work improved upon the current design by increasing the porosity by 46% and also increasing the ultimate compressive strength by 27%. The experimental data was found to match the theoretical strength in four designs, but deviate from the theoretical strength in five designs. The reasons for the deviations and their relation to the rapid prototyping manufacturing technique were discussed. The results of this work show that it is possible to increase the porosity and strength of a bone tissue engineering scaffold through simple iterations in architectural design.

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

  15. Polarized Raman spectroscopy of bone tissue: watch the scattering

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    Polarized Raman spectroscopy is widely used in the study of molecular composition and orientation in synthetic and natural polymer systems. Here, we describe the use of Raman spectroscopy to extract quantitative orientation information from bone tissue. Bone tissue poses special challenges to the use of polarized Raman spectroscopy for measurement of orientation distribution functions because the tissue is turbid and birefringent. Multiple scattering in turbid media depolarizes light and is potentially a source of error. Using a Raman microprobe, we show that repeating the measurements with a series of objectives of differing numerical apertures can be used to assess the contributions of sample turbidity and depth of field to the calculated orientation distribution functions. With this test, an optic can be chosen to minimize the systematic errors introduced by multiple scattering events. With adequate knowledge of the optical properties of these bone tissues, we can determine if elastic light scattering affects the polarized Raman measurements.

  16. 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

  17. 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

  18. A mechanism of bone tissue loss in monkeys (BION - 11).

    NASA Astrophysics Data System (ADS)

    Rodionova, N. V.; Oganov, V. S.

    The elucidation of mechanisms of bone tissue loss under the spaceflight conditions remains an actual problem until now It was established that primary reactions to a mechanical stress evolve at the cellular level therefore the main attention of the researchers was aimed at studying bone tissue cells and their interactions With the use of electron microscopy we studied osteoblasts osteocytes osteoclasts and stromal cells in bioptats of the iliac bone crest from monkeys flown on board the satellite guillemotleft BION - 11 guillemotright during 2 weeks The flight samples were compared with the vivarium and simulation controls The functional state of cells was evaluated by the degree of development of organelles for specific biosyntheses rough endoplasmic reticulum Golgy complex nucleus state interrelation with a mineralized matrix The analysis of the obtained results and data of other authors Klein -- Nulend et al 2003 etc permits to suppose that the following sequence of cell interactions underlies the bone tissue loss during mechanical stress microgravity reaction of mechano-sensitive osteocytes to a mechanical stimulus consisting in enhancement of osteolytic processes in cells which results in a partial bone tissue loss along the local unloading Simultaneously the modulating signals are transmitted through a system of canals and processes towards active osteoblasts surface osteocytes and bone marrow stromal cells as well As a reply to a mechanical stimulus there occurs a reduction slowing down of proliferation

  19. Silk fibroin as biomaterial for bone tissue engineering.

    PubMed

    Melke, Johanna; Midha, Swati; Ghosh, Sourabh; Ito, Keita; Hofmann, Sandra

    2016-02-01

    Silk fibroin (SF) is a fibrous protein which is produced mainly by silkworms and spiders. Its unique mechanical properties, tunable biodegradation rate and the ability to support the differentiation of mesenchymal stem cells along the osteogenic lineage, have made SF a favorable scaffold material for bone tissue engineering. SF can be processed into various scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified, which provides an impressive toolbox and allows SF scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing SF, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. Silk fibroin is a natural biomaterial with remarkable biomedical and mechanical properties which make it favorable for a broad range of bone tissue engineering applications. It can be processed into different scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified which provides a unique toolbox and allows silk fibroin scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing silk fibroin, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Stem cell derived endochondral cartilage stimulates bone healing by tissue transformation

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  2. Current Approaches to Bone Tissue Engineering: The Interface between Biology and Engineering.

    PubMed

    Li, Jiao Jiao; Ebied, Mohamed; Xu, Jen; Zreiqat, Hala

    2018-03-01

    The successful regeneration of bone tissue to replace areas of bone loss in large defects or at load-bearing sites remains a significant clinical challenge. Over the past few decades, major progress is achieved in the field of bone tissue engineering to provide alternative therapies, particularly through approaches that are at the interface of biology and engineering. To satisfy the diverse regenerative requirements of bone tissue, the field moves toward highly integrated approaches incorporating the knowledge and techniques from multiple disciplines, and typically involves the use of biomaterials as an essential element for supporting or inducing bone regeneration. This review summarizes the types of approaches currently used in bone tissue engineering, beginning with those primarily based on biology or engineering, and moving into integrated approaches in the areas of biomaterial developments, biomimetic design, and scalable methods for treating large or load-bearing bone defects, while highlighting potential areas for collaboration and providing an outlook on future developments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed Central

    Gadjanski, Ivana; Vunjak-Novakovic, Gordana

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2002-01-01

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

  5. Whole bone mechanics and bone quality.

    PubMed

    Cole, Jacqueline H; van der Meulen, Marjolein C H

    2011-08-01

    The skeleton plays a critical structural role in bearing functional loads, and failure to do so results in fracture. As we evaluate new therapeutics and consider treatments to prevent skeletal fractures, understanding the basic mechanics underlying whole bone testing and the key principles and characteristics contributing to the structural strength of a bone is critical. We therefore asked: (1) How are whole bone mechanical tests performed and what are the key outcomes measured? (2) How do the intrinsic characteristics of bone tissue contribute to the mechanical properties of a whole bone? (3) What are the effects of extrinsic characteristics on whole bone mechanical behavior? (4) Do environmental factors affect whole bone mechanical properties? We conducted a PubMed search using specific search terms and limiting our included articles to those related to in vitro testing of whole bones. Basic solid mechanics concepts are summarized in the context of whole bone testing and the determinants of whole bone behavior. Whole bone mechanical tests measure structural stiffness and strength from load-deformation data. Whole bone stiffness and strength are a function of total bone mass and the tissue geometric distribution and material properties. Age, sex, genetics, diet, and activity contribute to bone structural performance and affect the incidence of skeletal fractures. Understanding and preventing skeletal fractures is clinically important. Laboratory tests of whole bone strength are currently the only measures for in vivo fracture prediction. In the future, combined imaging and engineering models may be able to predict whole bone strength noninvasively.

  6. Drilling electrode for real-time measurement of electrical impedance in bone tissues.

    PubMed

    Dai, Yu; Xue, Yuan; Zhang, Jianxun

    2014-03-01

    In order to prevent possible damages to soft tissues, reliable monitoring methods are required to provide valuable information on the condition of the bone being cut. This paper describes the design of an electrical impedance sensing drill developed to estimate the relative position between the drill and the bone being drilled. The two-electrode method is applied to continuously measure the electrical impedance during a drill feeding movement: two copper wire brushes are used to conduct electricity in the rotating drill and then the drill is one electrode; a needle is inserted into the soft tissues adjacent to the bone being drilled and acts as another electrode. Considering that the recorded electrical impedance is correlated with the insertion depth of the drill, we theoretically calculate the electrode-tissue contact impedance and prove that the rate of impedance change varies considerably when the drill bit crosses the boundary between two different bone tissues. Therefore, the rate of impedance change is used to determine whether the tip of the drill is located in one of cortical bone, cancellous bone, and cortical bone near a boundary with soft tissue. In vitro experiments in porcine thoracic spines were performed to demonstrate the feasibility of the impedance sensing drill. The experimental results indicate that the drill, used with the proposed data-processing method, can provide accurate and reliable breakthrough detection in the bone-drilling process.

  7. 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.

  8. Normal bone and soft tissue distribution of fluorine-18-sodium fluoride and artifacts on 18F-NaF PET/CT bone scan: a pictorial review.

    PubMed

    Sarikaya, Ismet; Elgazzar, Abdelhamid H; Sarikaya, Ali; Alfeeli, Mahmoud

    2017-10-01

    Fluorine-18-sodium fluoride (F-NaF) PET/CT is a relatively new and high-resolution bone imaging modality. Since the use of F-NaF PET/CT has been increasing, it is important to accurately assess the images and be aware of normal distribution and major artifacts. In this pictorial review article, we will describe the normal uptake patterns of F-NaF in the bone tissues, particularly in complex structures, as well as its physiologic soft tissue distribution and certain artifacts seen on F-NaF PET/CT images.

  9. Harnessing the power of macrophages/monocytes for enhanced bone tissue engineering.

    PubMed

    Dong, Lei; Wang, Chunming

    2013-06-01

    Bone tissue engineering has attracted considerable attention as a promising treatment modality for severe bone degeneration. The pressing need for more sophisticated and fully functional bone substitutes has spurred a refocus on the development of bone constructs in a way more comparable to the physiological process. Current research is increasingly revealing the central roles of macrophages/monocytes in regulating bone development and repair, so we propose that these immunocytes can play a similar pivotal role in directing engineered bone regeneration. Accordingly, we discuss two possible strategies to exemplify how the distinctive power of macrophages/monocytes--particularly their cytokine-secretion ability and chemotactic response to foreign materials--can be harnessed to enhance the performance of bone tissue engineering applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. 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

  11. 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.

  12. Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force.

    PubMed

    Shimizu, Kazunori; Ito, Akira; Yoshida, Tatsuro; Yamada, Yoichi; Ueda, Minoru; Honda, Hiroyuki

    2007-08-01

    An in vitro reconstruction of three-dimensional (3D) tissues without the use of scaffolds may be an alternative strategy for tissue engineering. We have developed a novel tissue engineering strategy, termed magnetic force-based tissue engineering (Mag-TE), in which magnetite cationic liposomes (MCLs) with a positive charge at the liposomal surface, and magnetic force were used to construct 3D tissue without scaffolds. In this study, human mesenchymal stem cells (MSCs) magnetically labeled with MCLs were seeded onto an ultra-low attachment culture surface, and a magnet (4000 G) was placed on the reverse side. The MSCs formed multilayered sheet-like structures after a 24-h culture period. MSCs in the sheets constructed by Mag-TE maintained an in vitro ability to differentiate into osteoblasts, adipocytes, or chondrocytes after a 21-day culture period using each induction medium. Using an electromagnet, MSC sheets constructed by Mag-TE were harvested and transplanted into the bone defect in the crania of nude rats. Histological observation revealed that new bone surrounded by osteoblast-like cells was formed in the defect area 14 days after transplantation with MSC sheets, whereas no bone formation was observed in control rats without the transplant. These results indicated that Mag-TE could be used for the transplantation of MSC sheets using magnetite nanoparticles and magnetic force, providing novel methodology for bone tissue engineering.

  13. Biocompatibility and biodegradation studies of PCL/β-TCP bone tissue scaffold fabricated by structural porogen method.

    PubMed

    Lu, Lin; Zhang, Qingwei; Wootton, David; Chiou, Richard; Li, Dichen; Lu, Bingheng; Lelkes, Peter; Zhou, Jack

    2012-09-01

    Three-dimensional printer (3DP) (Z-Corp) is a solid freeform fabrication system capable of generating sub-millimeter physical features required for tissue engineering scaffolds. By using plaster composite materials, 3DP can fabricate a universal porogen which can be injected with a wide range of high melting temperature biomaterials. Here we report results toward the manufacture of either pure polycaprolactone (PCL) or homogeneous composites of 90/10 or 80/20 (w/w) PCL/beta-tricalcium phosphate (β-TCP) by injection molding into plaster composite porogens fabricated by 3DP. The resolution of printed plaster porogens and produced scaffolds was studied by scanning electron microscopy. Cytotoxicity test on scaffold extracts and biocompatibility test on the scaffolds as a matrix supporting murine osteoblast (7F2) and endothelial hybridoma (EAhy 926) cells growth for up to 4 days showed that the porogens removal process had only negligible effects on cell proliferation. The biodegradation tests of pure PCL and PCL/β-TCP composites were performed in DMEM with 10 % (v/v) FBS for up to 6 weeks. The PCL/β-TCP composites show faster degradation rate than that of pure PCL due to the addition of β-TCP, and the strength of 80/20 PCL/β-TCP composite is still suitable for human cancellous bone healing support after 6 weeks degradation. Combining precisely controlled porogen fabrication structure, good biocompatibility, and suitable mechanical properties after biodegradation, PCL/β-TCP scaffolds fabricated by 3DP porogen method provide essential capability for bone tissue engineering.

  14. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering

    PubMed Central

    Winkler, T.; Sass, F. A.; Schmidt-Bleek, K.

    2018-01-01

    Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

  15. Investigation of composition and structure of spongy and hard bone tissue using FTIR spectroscopy, XRD and SEM

    NASA Astrophysics Data System (ADS)

    Al-Akhras, M.-Ali H.; Hasan Qaseer, M. K.; Albiss, B. A.; Alebrhim, M. Anwar; Gezawa, Umar S.

    2018-02-01

    Valuable structural and chemical features can be obtained for spongy and hard bone by infrared spectroscopy and X-ray diffraction. A better understanding of chemical and structural differences between spongy and hard bone is a very important contributor to bone quality. Our data according to IR data showed that the collagen cross-links occurred to be higher in spongy bone, and crystallinity was lower in spongy bone. Deconvolution of the infrared band near 870 cm-1 reveals evidence for A2-type carbonate substitution on hydroxyapatite of spongy bone in addition to the A and B type carbonate substitution that are also found in hard bone. IR and XRD data confirmed the results of each other since full width at half maximum of 002-apatite pattern of XRD showed that the crystallinity was lower in spongy bone. The microstructure was examined by using scanning electron microscope and the result showed that the lattice of thin threads in spongy bone and is less dense than hard bone.

  16. Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study

    PubMed Central

    Casazza, K; Hanks, LJ; Hidalgo, B; Hu, HH; Affuso, O

    2011-01-01

    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 minutes 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 ten 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 physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization. PMID:21939791

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

    PubMed

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

    2012-02-01

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

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

    PubMed

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

    2014-07-01

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

  19. Biodegradation, biocompatibility, and osteoconduction evaluation of collagen-nanohydroxyapatite cryogels for bone tissue regeneration.

    PubMed

    Salgado, Christiane Laranjo; Grenho, Liliana; Fernandes, Maria Helena; Colaço, Bruno Jorge; Monteiro, Fernando Jorge

    2016-01-01

    Designing biomimetic biomaterials inspired by the natural complex structure of bone and other hard tissues is still a challenge nowadays. The control of the biomineralization process onto biomaterials should be evaluated before clinical application. Aiming at bone regeneration applications, this work evaluated the in vitro biodegradation and interaction between human bone marrow stromal cells (HBMSC) cultured on different collagen/nanohydroxyapatite cryogels. Cell proliferation, differentiation, morphology, and metabolic activity were assessed through different protocols. All the biocomposite materials allowed physiologic apatite deposition after incubation in simulated body fluid and the cryogel with the highest nanoHA content showed to have the highest mechanical strength (DMA). The study clearly showed that the highest concentration of nanoHA granules on the cryogels were able to support cell type's survival, proliferation, and individual functionality in a monoculture system, for 21 days. In fact, the biocomposites were also able to differentiate HBMSCs into osteoblastic phenotype. The composites behavior was also assessed in vivo through subcutaneous and bone implantation in rats to evaluate its tissue-forming ability and degradation rate. The cryogels Coll/nanoHA (30 : 70) promoted tissue regeneration and adverse reactions were not observed on subcutaneous and bone implants. The results achieved suggest that scaffolds of Coll/nanoHA (30 : 70) should be considered promising implants for bone defects that present a grotto like appearance with a relatively small access but a wider hollow inside. This material could adjust to small dimensions and when entering into the defect, it could expand inside and remain in close contact with the defect walls, thus ensuring adequate osteoconductivity. © 2015 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2014-01-01

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

  1. 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.

  2. 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

  3. Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

    PubMed

    Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

    2011-11-01

    Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Tricalcium phosphate and glutaraldehyde crosslinked gelatin incorporating bone morphogenetic protein--a viable scaffold for bone tissue engineering.

    PubMed

    Yang, Shu-Hua; Hsu, Chung-King; Wang, Kuo-Cheng; Hou, Sheng-Mou; Lin, Feng-Huei

    2005-07-01

    Bone defects caused by various etiologies must be filled with suitable substances to promote bone repair. Autogenous iliac crest graft is most frequently used, but is often associated with morbidities. Several bone graft substitutes have been developed to provide osteoconductive matrices as well as to enhance osteoinductivity. A tricalcium phosphate and glutaraldehyde crosslinked gelatin (GTG) scaffold, incorporated with bone morphogenetic proteins (BMPs), was developed to provide an alternative mean of bone tissue engineering. This study investigated differences between GTG and BMP-4 immobilized GTG (GTG-BMP) scaffolds on neonatal rat calvaria osteoblast activities. The GTG scaffold possessed an average pore size of 200 microm and a porosity of 75%. HE staining revealed uniform cell distribution throughout the scaffold 24 h post cell seeding. Alkaline phosphatase (ALP) activity of the GTG samples increased initially and then stabilized at 3 weeks postseeding. ALP activity of the GTG-BMP samples was similar to that of the GTG samples in the second and third weeks, but it continued increasing and became significantly greater than that of the GTG samples by the fourth week. Gla-type osteocalcin (Gla-OC) activity of the GTG-BMP samples was initially lower, but also became significantly greater than that of the GTG samples by the fourth week. An HE stain revealed greater numbers of attached cells and a richer matrix deposits in the GTG-BMP samples. A von Kossa stain showed larger mineralizing nodules, in greater numbers, after 4 weeks of in vitro cultivation. These findings suggest that the GTG scaffold provides an excellent porous structure, conductive to greater cell attachment and osteoblast differentiation, and that utility can be significantly enhanced by the inclusion of BMPs. A GTG-BMP scaffold holds promise as a superior bioactive material for bone tissue engineering. Copyright 2005 Wiley Periodicals, Inc.

  6. Bioinspired double polysaccharides-based nanohybrid scaffold for bone tissue engineering.

    PubMed

    Fan, Tiantang; Chen, Jingdi; Pan, Panpan; Zhang, Yujue; Hu, Yimin; Liu, Xiaocui; Shi, Xuetao; Zhang, Qiqing

    2016-11-01

    The fabrication of bone scaffolds with interconnected porous structure, adequate mechanical properties and excellent biocompatibility presents a great challenge. Herein, a hybrid nanostructured chitosan/chondroitin sulfate/hydroxyapatite (ChS/CSA/HAP) in situ composite scaffold was prepared by in situ fabrication and freeze-drying technique. The composition and morphology of scaffold were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). It proved that the low crystallinity of HAP crystals were uniformly distributed in ChS/CSA organic matrix and the nanostructured hybrid scaffold exhibited good mechanical property. The biocompatibility and in vitro bioactivity were detected by MTT-assay, maturation (alkaline phosphatase (ALP) activity), Hoechst 33258 and PI fluorescence staining. In vitro tests indicated that the hybrid scaffold not only promoted the adhesion and proliferation of osteoblasts, but also improved the growth of the osteoblasts. Therefore, it is promising for bone repair application in bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Effect of weightlessness on mineral saturation of bone tissue

    NASA Technical Reports Server (NTRS)

    Krasnykh, I. G.

    1975-01-01

    X-ray photometry of bone density established dynamic changes in mineral saturation of bone tissues for Soyuz spacecraft and Salyut orbital station crews. Calcaneus optical bone densities in all crew members fell below initial values; an increase in spacecrew exposure time to weightlessness conditions also increased the degree of decalcification. Demineralization under weightlessness conditions took place at a higher rate than under hypodynamia.

  8. In vivo bone tissue response to a canasite glass-ceramic.

    PubMed

    da Rocha Barros, V M; Salata, L A; Sverzut, C E; Xavier, S P; van Noort, R; Johnson, A; Hatton, P V

    2002-07-01

    The aim of this study was to determine the biocompatibility and osteoconductive potential of a high-strength canasite glass ceramic. Glass-ceramic rods were produced using the lost-wax casting technique and implanted in the mid-shafts rabbit femurs. Implants were harvested at 4, 13 and 22 weeks and prepared for light and electron microscopy. Hydroxyapatite was used as a control material. Hydroxyapatite implants were surrounded by new mineralised bone tissue after 4 weeks of implantation. The amount of bone surrounding the implant increased slightly at 13 weeks. In contrast, canasite glass and glass ceramic implants were almost entirely surrounded by soft tissue during all the time periods. Close contact between bone and canasite glass-ceramic implant without the intervening fibrous tissue was observed in only a few regions. The canasite formulation evaluated was not osteoconductive and appeared to degrade in the biological environment. It was therefore concluded that the canasite formulation used was unsuitable for use as implant. Further work is required to improve the biocompatibility of these materials with bone tissue. It is possible that this could be achieved by reducing the solubility of the glass and glass ceramic.

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

    PubMed

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

    2017-06-01

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

  10. 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.

  11. Mag-seeding of rat bone marrow stromal cells into porous hydroxyapatite scaffolds for bone tissue engineering.

    PubMed

    Shimizu, Kazunori; Ito, Akira; Honda, Hiroyuki

    2007-09-01

    Bone tissue engineering has been investigated as an alternative strategy for autograft transplantation. In the process of tissue engineering, cell seeding into three-dimensional (3-D) scaffolds is the first step for constructing 3-D tissues. We have proposed a methodology of cell seeding into 3-D porous scaffolds using magnetic force and magnetite nanoparticles, which we term Mag-seeding. In this study, we applied this Mag-seeding technique to bone tissue engineering using bone marrow stromal cells (BMSCs) and 3-D hydroxyapatite (HA) scaffolds. BMSCs were magnetically labeled with our original magnetite cationic liposomes (MCLs) having a positive surface charge to improve adsorption to cell surface. Magnetically labeled BMSCs were seeded onto a scaffold, and a 1-T magnet was placed under the scaffold. By using Mag-seeding, the cells were successfully seeded into the internal space of scaffolds with a high cell density. The cell seeding efficiency into HA scaffolds by Mag-seeding was approximately threefold larger than that by static-seeding (conventional method, without a magnet). After a 14-d cultivation period using the osteogenic induction medium by Mag-seeding, the level of two representative osteogenic markers (alkaline phosphatase and osteocalcin) were significantly higher than those by static-seeding. These results indicated that Mag-seeding of BMSCs into HA scaffolds is an effective approach to bone tissue engineering.

  12. [Research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering].

    PubMed

    Zhang, Haifeng; Han, Dong

    2014-09-01

    To review the application and research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering. The original articles about in vivo bioreactor that can enhance vascularization of tissue engineered bone were extensively reviewed and analyzed. The in vivo bioreactor can be created by periosteum, muscle, muscularis membrane, and fascia flap as well as biomaterials. Using in vivo bioreactor can effectively promote the establishment of a microcirculation in the tissue engineered bones, especially for large bone defects. However, main correlative researches, currently, are focused on animal experiments, more clinical trials will be carried out in the future. With the rapid development of related technologies of bone tissue engineering, the use of in vivo bioreactor will to a large extent solve the bottleneck limitations and has the potential values for clinical application.

  13. Biomimetic fabrication of a three-level hierarchical calcium phosphate/collagen/hydroxyapatite scaffold for bone tissue engineering.

    PubMed

    Zhou, Changchun; Ye, Xingjiang; Fan, Yujiang; Ma, Liang; Tan, Yanfei; Qing, Fangzu; Zhang, Xingdong

    2014-09-01

    A three-level hierarchical calcium phosphate/collagen/hydroxyapatite (CaP/Col/HAp) scaffold for bone tissue engineering was developed using biomimetic synthesis. Porous CaP ceramics were first prepared as substrate materials to mimic the porous bone structure. A second-level Col network was then composited into porous CaP ceramics by vacuum infusion. Finally, a third-level HAp layer was achieved by biomimetic mineralization. The three-level hierarchical biomimetic scaffold was characterized using scanning electron microscopy, energy-dispersive x-ray spectra, x-ray diffraction and Fourier transform infrared spectroscopy, and the mechanical properties of the scaffold were evaluated using dynamic mechanical analysis. The results show that this scaffold exhibits a similar structure and composition to natural bone tissues. Furthermore, this three-level hierarchical biomimetic scaffold showed enhanced mechanical strength compared with pure porous CaP scaffolds. The biocompatibility and osteoinductivity of the biomimetic scaffolds were evaluated using in vitro and in vivo tests. Cell culture results indicated the good biocompatibility of this biomimetic scaffold. Faster and increased bone formation was observed in these scaffolds following a six-month implantation in the dorsal muscles of rabbits, indicating that this biomimetic scaffold exhibits better osteoinductivity than common CaP scaffolds.

  14. Design and optimization of a tissue-engineered bone graft substitute

    NASA Astrophysics Data System (ADS)

    Shimko, Daniel Andrew

    2004-12-01

    In 2000, 3.1 million surgical procedures on the musculoskeletal system were reported in the United States. For many of these cases, bone grafting was essential for successful fracture stabilization. Current techniques use intact bone obtained either from the patient (autograft) or a cadaver (allograft) to repair large defects, however, neither source is optimal. Allografts suffer integration problems, and for autografts, the tissue supply is limited. Because of these shortcomings, and the high demand for graft tissues, alternatives are being explored. To successfully engineer a bone graft replacement, one must employ a three pronged research approach, addressing (1) the cells that will inhabit the new tissue, (2) the culture environment that these cells will be exposed to, and (3) the scaffold in which these cells will reside. The work herein examines each of these three aspects in great detail. Both adult and embryonic stem cells (ESCs) were considered for the tissue-engineered bone graft. Both exhibited desirable qualities, however, neither were optimal in all categories examined. In the end, the possibility of teratoma formation and ethical issues surrounding ESCs, made the use of adult marrow-derived stem cells in the remaining experiments obligatory. In subsequent experiments, the adult stem cells' ability to form bone was optimized. Basic fibroblast growth factor, fetal bovine serum, and extracellular calcium supplementation studies were all performed. Ultimately, adult stem cells cultured in alpha-MEM supplemented with 10% fetal bovine serum, 10mM beta-glycerophosphate, 10nM dexamethasone, 50mug/ml ascorbic acid, 1%(v/v) antibiotic/antimycotic, and 10.4mM CaCl2 performed the best, producing nearly four times more mineral than any other medium formulation. Several scaffolds were then investigated including those fabricated from poly(alpha-hydroxy esters), tantalum, and poly-methylmethacrylate. In the final study, the most appealing cell type, medium

  15. In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices.

    PubMed

    Lu, Helen H; Kofron, Michelle D; El-Amin, Saadiq F; Attawia, Mohammed A; Laurencin, Cato T

    2003-06-13

    Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives to autogenous bone, the grafting standard in osseous repair. The objective of this study was to examine the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype and in vitro bone formation by muscle-derived cells. Specifically, we evaluated the ability of bone morphogenetic protein-7 (BMP-7), delivered from a poly(lactide-co-glycolide) (PLAGA) matrix, to induce the differentiation of cells derived from rabbit skeletal muscle into osteoblast-like cells and subsequently form mineralized tissue. Results confirmed that muscle-derived cells attached and proliferated on the PLAGA substrates. BMP-7 released from PLAGA induced the muscle-derived cells to increase bone marker expression and form mineralized cultures. These results demonstrate the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype by muscle-derived cells and present a new paradigm for bone tissue engineering.

  16. 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

  17. 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.

  18. A novel use of 3D printing model demonstrates the effects of deteriorated trabecular bone structure on bone stiffness and strength.

    PubMed

    Barak, Meir Max; Black, Margaret Arielle

    2018-02-01

    Trabecular bone structure is crucial to normal mechanical behavior of bones. Studies have shown that osteoporosis negatively affects trabecular bone structure, mainly by reducing bone volume fraction (BV/TV) and thus increasing fracture risk. One major limitation in assessing and quantifying the effect of this structural deterioration is that no two trabecular structures are identical. Thus, when we compare a group of healthy bones against a different group of bones that experienced resorption (i.e. decreased BV/TV) we only discover an "average" mechanical effect. It is impossible to quantify the mechanical effect of individual structural deterioration for each sample, simply because we never have the same sample in both states (intact and deteriorated structure). 3D printing is a new technology that can assist in overcoming this issue. Here we report a preliminary study that compares a healthy 3D printed trabecular bone model with the same model after bone resorption was simulated. Since the deteriorated structural bone model is derived from the healthy one, it is possible to directly estimate (percentage wise) the decrease of tissue stiffness and strength as a result of bone resorption for this specific structure. Our results demonstrate that a relatively small decrease in BV/TV (about 8%) leads to a dramatic decrease in structural strength (24%) and structural stiffness (17%), (P < 0.01). Structural strength decreased from an average of 9.14 ± 2.85MPa to 6.97 ± 2.44MPa, while structural stiffness decreased from an average of 282.5 ± 63.4N/mm to 233.8 ± 51.2N/mm. This study demonstrates that 3D printing is a novel and valuable tool for quantifying the effect of structural deterioration on the mechanical properties of trabecular bone. In the future, this approach may help us attain better personal fracture risk assessments by CT scanning, 3D printing and mechanically testing individual bone replicas from patients suffering excessive bone resorption. Copyright

  19. Characterization of Microgravity Effects on Bone Structure and Strength Using Fractal Analysis

    NASA Technical Reports Server (NTRS)

    Acharya, Raj S.; Shackelford, Linda

    1996-01-01

    Protecting humans against extreme environmental conditions requires a thorough understanding of the pathophysiological changes resulting from the exposure to those extreme conditions. Knowledge of the degree of medical risk associated with the exposure is of paramount importance in the design of effective prophylactic and therapeutic measures for space exploration. Major health hazards due o musculoskeletal systems include the signs and symptoms of hypercalciuria, lengthy recovery of lost bone tissue after flight, the possibility of irreversible trabecular bone loss, the possible effect of calcification in the soft tissues, and the possible increase in fracture potential. In this research, we characterize the trabecular structure with the aid of fractal analysis. Our research to relate local trabecular structural information to microgravity conditions is an important initial step in understanding the effect of microgravity and countermeasures on bone condition and strength. The proposed research is also closely linked with Osteoporosis and will benefit the general population.

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

    PubMed

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

    2017-04-01

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

  1. Changes in bone tissue under conditions of hypokinesia and in connection with age

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

    X-ray micrography was used to study the optical density of the blackening of X-ray photographs made of five bones in 9 young people (ages 24 to 29) before and after strict bed rest for 16 to 37 days. Photometric studies of the X-ray film determined the relative concentration of bone structure before and after hypokinesia. In addition, the bone tissues of 25 cadavers of practically healthy individuals (aged 18 to 70) who died from injuries were investigated using X-ray structural analysis. Results show that the reaction to the state of hypokinesia is not uniform in different individuals and is quite often directly reversed. It was established that pronounced osteoporosis can be found in a relatively short time after conditions of hypokinesia in healthy young individuals. Results show that the stabilization of the crystalline structure of hydroxyapatite, especially its crystal formation, is finished by the age of 20 to 25. From 25 to 60, the crystal lattice remains in stable condition but X-ray analysis shows a reduction in the hydroxyapatite density.

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

    PubMed

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

    2013-02-01

    It has been hypothesised that among different human subjects, the bone tissue quality varies as a function of the bone segment morphology. The aim of this study was to assess and compare the quality, evaluated in terms of hardness of packages of lamellae, of cortical and trabecular bones, at different anatomical sites within the human skeleton. The contralateral six long bones of an old human subject were indented at different levels along the diaphysis and at both epiphyses of each bone. Hardness value, which is correlated to the degree of mineralisation, of both cortical and trabecular bone tissues was calculated for each indentation location. It was found that the cortical bone tissue was harder (+18%) than the trabecular one. In general, the bone hardness was found to be locally highly heterogeneous. In fact, considering one single slice obtained for a bone segment, the coefficient of variation of the hardness values was up to 12% for cortical bone and up to 17% for trabecular bone. However, the tissue hardness was on average quite homogeneous within and among the long bones of the studied donor, although differences up to 9% among levels and up to 7% among bone segments were found. These findings seem not to support the mentioned hypothesis, at least not for the long bones of an old subject.

  3. 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.

  4. Bisphosphonate-Based Strategies for Bone Tissue Engineering and Orthopedic Implants

    PubMed Central

    Cattalini, Juan Pablo; Boccaccini, Aldo R.; Lucangioli, Silvia

    2012-01-01

    Bisphosphonates (BPs) are a group of well-established drugs that are applied in the development of metabolic bone disorder-related therapies. There is increasing interest also in the application of BPs in the context of bone tissue engineering, which is the topic of this review, in which an extensive overview of published studies on the development and applications of BPs-based strategies for bone regeneration is provided with special focus on the rationale for the use of different BPs in three-dimensional (3D) bone tissue scaffolds. The different alternatives that are investigated to address the delivery and sustained release of these therapeutic drugs in the nearby tissues are comprehensively discussed, and the most significant published approaches on bisphosphonate-conjugated drugs in multifunctional 3D scaffolds as well as the role of BPs within coatings for the improved fixation of orthopedic implants are presented and critically evaluated. Finally, the authors' views regarding the remaining challenges in the fields and directions for future research efforts are highlighted. PMID:22440082

  5. Yb3+/Ho3+ Co-Doped Apatite Upconversion Nanoparticles to Distinguish Implanted Material from Bone Tissue.

    PubMed

    Li, Xiyu; Chen, Haifeng

    2016-10-07

    The exploration of bone reconstruction with time requires the combination of a biological method and a chemical technique. Lanthanide Yb 3+ and Ho 3+ co-doped fluorapatite (FA:Yb 3+ /Ho 3+ ) and hydroxyapatite (HA:Yb 3+ /Ho 3+ ) particles with varying dopant concentrations were prepared by hydrothermal synthesis and thermal activation. Controllable green and red upconversion emissions were generated under 980 nm near-infrared excitation; the FA:Yb 3+ /Ho 3+ particles resulted in superior green luminescence, while HA:Yb 3+ /Ho 3+ dominated in red emission. The difference in the green and red emission behavior was dependent on the lattice structure and composition. Two possible lattice models were proposed for Yb 3+ /Ho 3+ co-doped HA and FA along the hydroxyl channel and fluorine channel of the apatite crystal structure. We first reported the use of the upconversion apatite particles to clearly distinguish implanted material from bone tissue on stained histological sections of harvested in vivo samples. The superposition of the tissue image and material image is a creative method to show the material-tissue distribution and interrelation. The upconversion apatite particles and image superposition method provide a novel strategy for long-term discriminable fluorescence tracking of implanted material or scaffold during bone regeneration.

  6. Reduced tissue hardness of trabecular bone is associated with severe osteoarthritis.

    PubMed

    Dall'Ara, Enrico; Ohman, Caroline; Baleani, Massimiliano; Viceconti, Marco

    2011-05-17

    This study investigated whether changes in hardness of human trabecular bone are associated with osteoarthritis. Twenty femoral heads extracted from subjects without musculoskeletal diseases (subject age: 49-83 years) and twenty femoral heads extracted from osteoarthritic subjects (subject age: 42-85 years) were tested. Sixty indentations were performed along the main trabecular direction of each sample at a fixed relative distance. Two microstructures were found on the indenting locations: packs of parallel-lamellae (PL) and secondary osteons (SO). A 25gf load was applied for 15s and the Vickers Hardness (HV) was assessed. Trabecular tissue extracted from osteoarthritic subjects was found to be about 13% less hard compared to tissue extracted from non-pathologic subjects. However, tissue hardness was not significantly affected by gender or age. The SO was 10% less hard than the PL for both pathologic and non-pathologic tissues. A hardness of 34.1HV for PL and 30.8HV for SO was found for the non-pathologic tissue. For osteoarthritic tissue, the hardness was 30.2HV for PL and 27.1HV for SO. In the bone tissue extracted from osteoarthritic subjects the occurrence of indenting a SO (28%) was higher than that observed in the non-pathological tissue (15%). Osteoarthritis is associated with reduced tissue hardness and alterations in microstructure of the trabecular bone tissue. Gender does not significantly affect trabecular bone hardness either in non-pathological or osteoarthritic subjects. A similar conclusion can be drawn for age, although a larger donor sample size would be necessary to definitively exclude the existence of a slight effect. Copyright © 2011. Published by Elsevier Ltd.

  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. A bioprintable form of chitosan hydrogel for bone tissue engineering.

    PubMed

    Demirtaş, Tuğrul Tolga; Irmak, Gülseren; Gümüşderelioğlu, Menemşe

    2017-07-13

    Bioprinting can be defined as 3D patterning of living cells and other biologics by filling and assembling them using a computer-aided layer-by-layer deposition approach to fabricate living tissue and organ analogs for tissue engineering. The presence of cells within the ink to use a 'bio-ink' presents the potential to print 3D structures that can be implanted or printed into damaged/diseased bone tissue to promote highly controlled cell-based regeneration and remineralization of bone. In this study, it was shown for the first time that chitosan solution and its composite with nanostructured bone-like hydroxyapatite (HA) can be mixed with cells and printed successfully. MC3T3-E1 pre-osteoblast cell laden chitosan and chitosan-HA hydrogels, which were printed with the use of an extruder-based bioprinter, were characterized by comparing these hydrogels to alginate and alginate-HA hydrogels. Rheological analysis showed that all groups had viscoelastic properties. It was also shown that under simulated physiological conditions, chitosan and chitosan-HA hydrogels were stable. Also, the viscosity values of the bio-solutions were in an applicable range to be used in 3D bio-printers. Cell viability and proliferation analyses documented that after printing with bio-solutions, cells continued to be viable in all groups. It was observed that cells printed within chitosan-HA composite hydrogel had peak expression levels for early and late stages osteogenic markers. It was concluded that cells within chitosan and chitosan-HA hydrogels had mineralized and differentiated osteogenically after 21 days of culture. It was also discovered that chitosan is superior to alginate, which is the most widely used solution preferred in bioprinting systems, in terms of cell proliferation and differentiation. Thus, applicability and printability of chitosan as a bio-printing solution were clearly demonstrated. Furthermore, it was proven that the presence of bone-like nanostructured HA in

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

    PubMed Central

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

    2018-01-01

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

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. Practical use of imaging technique for management of bone and soft tissue tumors.

    PubMed

    Miwa, Shinji; Otsuka, Takanobu

    2017-05-01

    Imaging modalities including radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are necessary for the diagnosis of bone and soft tissue tumors. The history of imaging began with the discovery of X-rays in the 19th century. The development of CT, MRI, ultrasonography, and positron emission tomography (PET) have improved the management of bone and soft tissue tumors. X-ray imaging and CT scans enable the evaluation of bone destruction, periosteal reaction, sclerotic changes in lesions, condition of cortical bone, and ossification. MRI enables the assessment of tissue characteristics, tumor extent, and the reactive areas. Functional imaging modalities including 201 thallium ( 201 Tl) scintigraphy can be used to differentiate benign lesions from malignant lesions and to assess chemotherapeutic effects. Real-time assessment of soft tissue tumors by ultrasonography enables accurate and safe performance of surgery and biopsy. This article describes useful imaging modalities and characteristic findings in the management of bone and soft tissue tumors. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  13. 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

  14. Controlled release of drugs in electrosprayed nanoparticles for bone tissue engineering.

    PubMed

    Jayaraman, Praveena; Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Becker, David Laurence; Ramakrishna, Seeram; Srinivasan, Dinesh Kumar

    2015-11-01

    Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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

  16. Hard tissue regeneration using bone substitutes: an update on innovations in materials.

    PubMed

    Sarkar, Swapan Kumar; Lee, Byong Taek

    2015-05-01

    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.

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

    PubMed

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

    2018-01-01

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

  18. 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

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

    PubMed

    Abrahamsson, Peter; Isaksson, Sten; Andersson, Gunilla

    2011-11-01

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

  20. Guidelines for managing data and processes in bone and cartilage tissue engineering.

    PubMed

    Viti, Federica; Scaglione, Silvia; Orro, Alessandro; Milanesi, Luciano

    2014-01-01

    In the last decades, a wide number of researchers/clinicians involved in tissue engineering field published several works about the possibility to induce a tissue regeneration guided by the use of biomaterials. To this aim, different scaffolds have been proposed, and their effectiveness tested through in vitro and/or in vivo experiments. In this context, integration and meta-analysis approaches are gaining importance for analyses and reuse of data as, for example, those concerning the bone and cartilage biomarkers, the biomolecular factors intervening in cell differentiation and growth, the morphology and the biomechanical performance of a neo-formed tissue, and, in general, the scaffolds' ability to promote tissue regeneration. Therefore standards and ontologies are becoming crucial, to provide a unifying knowledge framework for annotating data and supporting the semantic integration and the unambiguous interpretation of novel experimental results. In this paper a conceptual framework has been designed for bone/cartilage tissue engineering domain, by now completely lacking standardized methods. A set of guidelines has been provided, defining the minimum information set necessary for describing an experimental study involved in bone and cartilage regenerative medicine field. In addition, a Bone/Cartilage Tissue Engineering Ontology (BCTEO) has been developed to provide a representation of the domain's concepts, specifically oriented to cells, and chemical composition, morphology, physical characterization of biomaterials involved in bone/cartilage tissue engineering research. Considering that tissue engineering is a discipline that traverses different semantic fields and employs many data types, the proposed instruments represent a first attempt to standardize the domain knowledge and can provide a suitable means to integrate data across the field.

  1. Hydrophobicity as a design criterion for polymer scaffolds in bone tissue engineering.

    PubMed

    Jansen, Edwin J P; Sladek, Raymond E J; Bahar, Hila; Yaffe, Avinoam; Gijbels, Marion J; Kuijer, Roel; Bulstra, Sjoerd K; Guldemond, Nick A; Binderman, Itzhak; Koole, Leo H

    2005-07-01

    Porous polymeric scaffolds play a key role in most tissue-engineering strategies. A series of non-degrading porous scaffolds was prepared, based on bulk-copolymerisation of 1-vinyl-2-pyrrolidinone (NVP) and n-butyl methacrylate (BMA), followed by a particulate-leaching step to generate porosity. Biocompatibility of these scaffolds was evaluated in vitro and in vivo. Furthermore, the scaffold materials were studied using the so-called demineralised bone matrix (DBM) as an evaluation system in vivo. The DBM, which is essentially a part of a rat femoral bone after processing with mineral acid, provides a suitable environment for ectopic bone formation, provided that the cavity of the DBM is filled with bone marrow prior to subcutaneous implantation in the thoracic region of rats. Various scaffold materials, differing with respect to composition and, hence, hydrophilicity, were introduced into the centre of DBMs. The ends were closed with rat bone marrow, and ectopic bone formation was monitored after 4, 6, and 8 weeks, both through X-ray microradiography and histology. The 50:50 scaffold particles were found to readily accommodate formation of bone tissue within their pores, whereas this was much less the case for the more hydrophilic 70:30 counterpart scaffolds. New healthy bone tissue was encountered inside the pores of the 50:50 scaffold material, not only at the periphery of the constructs but also in the center. Active osteoblast cells were found at the bone-biomaterial interfaces. These data indicate that the hydrophobicity of the biomaterial is, most likely, an important design criterion for polymeric scaffolds which should promote the healing of bone defects. Furthermore, it is argued that stable, non-degrading porous biomaterials, like those used in this study, provide an important tool to expand our comprehension of the role of biomaterials in scaffold-based tissue engineering approaches.

  2. In vivo response to starch-based scaffolds designed for bone tissue engineering applications.

    PubMed

    Salgado, A J; Coutinho, O P; Reis, R L; Davies, J E

    2007-03-15

    Our purpose was to evaluate the in vivo endosseous response to three starch-based scaffolds implanted in rats (n = 54). We implanted the three scaffold groups; a 50/50 (wt %) blend of corn starch and ethylene-vinyl alcohol (SEVA-C), the same composition coated with a biomimetic calcium phosphate (Ca-P) layer (SEVA-C/CaP), and a 50/50 (wt %) blend of corn starch and cellulose acetate (SCA), all produced by extrusion with blowing agents, into distal femurs proximal to the epiphyseal plate, for 1, 3, or 6 weeks. Our results showed that at 1 week considerable reparative bone formed around all scaffold groups, although the bone was separated from the scaffold by an intervening soft tissue interfacial zone that comprised two distinct compartments: the surface of the scaffold was occupied by multinucleate giant cells and the compartment between these cells and the surrounding bone was occupied by a streaming fibrous-like tissue. The extracellular matrix of the latter was continuous with the extracellular bone matrix itself, labeled positively for osteocalcin and appeared mineralized by back-scattered electron imaging. All three scaffolds showed a similar tissue response, with the soft tissue interface diminishing with time. No bone contact was observed with SEVA-C at any time point, only transitory bone contact was observed with SEVA-C/CaP at 3 weeks, but SCA exhibited direct bone contact at 6 weeks where 56.23 +/- 6.46% of the scaffold surface was occupied by bone. We conclude that all materials exhibited a favorable bony response and that the rapidly forming initial "connective tissue" seen around all scaffolds was a very early form of bone formation.

  3. Enhanced osteogenesis of β-tricalcium phosphate reinforced silk fibroin scaffold for bone tissue biofabrication.

    PubMed

    Lee, Dae Hoon; Tripathy, Nirmalya; Shin, Jae Hun; Song, Jeong Eun; Cha, Jae Geun; Min, Kyung Dan; Park, Chan Hum; Khang, Gilson

    2017-02-01

    Scaffolds, used for tissue regeneration are important to preserve their function and morphology during tissue healing. Especially, scaffolds for bone tissue engineering should have high mechanical properties to endure load of bone. Silk fibroin (SF) from Bombyx mori silk cocoon has potency as a type of biomaterials in the tissue engineering. β-tricalcium phosphate (β-TCP) as a type of bioceramics is also critical as biomaterials for bone regeneration because of its biocompatibility, osteoconductivity, and mechanical strength. The aim of this study was to fabricate three-dimensional SF/β-TCP scaffolds and access its availability for bone grafts through in vitro and in vivo test. The scaffolds were fabricated in each different ratios of SF and β-TCP (100:0, 75:25, 50:50, 25:75). The characterizations of scaffolds were conducted by FT-IR, compressive strength, porosity, and SEM. The in vitro and in vivo tests were carried out by MTT, ALP, RT-PCR, SEM, μ-CT, and histological staining. We found that the SF/β-TCP scaffolds have high mechanical strength and appropriate porosity for bone tissue engineering. The study showed that SF/β-TCP (75:25) scaffold exhibited the highest osteogenesis compared with other scaffolds. The results suggested that SF/β-TCP (75:25) scaffold can be applied as one of potential bone grafts for bone tissue engineering. Copyright © 2016. Published by Elsevier B.V.

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

    PubMed

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

    2016-06-21

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

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

    PubMed Central

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

    2016-01-01

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

  6. 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

  7. Gene Therapy of Bone Morphogenetic Protein for Periodontal Tissue Engineering

    PubMed Central

    Jin, Q-M.; Anusaksathien, O.; Webb, S.A.; Rutherford, R.B.; Giannobile, W.V.

    2009-01-01

    Background The reconstruction of lost periodontal support including bone, ligament, and cementum is a major goal of therapy. Bone morphogenetic proteins (BMPs) have shown much potential in the regeneration of the periodontium. Limitations of BMP administration to periodontal lesions include need for high-dose bolus delivery, BMP transient biological activity, and low bioavailability of factors at the wound site. Gene transfer offers promise as an alternative treatment strategy to deliver BMPs to periodontal tissues. Methods This study utilized ex vivo BMP-7 gene transfer to stimulate tissue engineering of alveolar bone wounds. Syngeneic dermal fibroblasts (SDFs) were transduced ex vivo with adenoviruses encoding either green fluorescent protein (Ad-GFP or control virus), BMP-7 (Ad-BMP-7), or an antagonist of BMP bioactivity, noggin (Ad-noggin). Transduced cells were seeded onto gelatin carriers and then transplanted to large mandibular alveolar bone defects in a rat wound repair model. Results Ad-noggin treatment tended to inhibit osteogenesis as compared to the control-treated and Ad-BMP-7-treated specimens. The osseous lesions treated by Ad-BMP-7 gene delivery demonstrated rapid chrondrogenesis, with subsequent osteogenesis, cementogenesis and predictable bridging of the periodontal bone defects. Conclusion These results demonstrate the first successful evidence of periodontal tissue engineering using ex vivo gene transfer of BMPs and offers a new approach for repairing periodontal defects. PMID:12666709

  8. Highly porous scaffolds of PEDOT:PSS for bone tissue engineering.

    PubMed

    Guex, Anne Géraldine; Puetzer, Jennifer L; Armgarth, Astrid; Littmann, Elena; Stavrinidou, Eleni; Giannelis, Emmanuel P; Malliaras, George G; Stevens, Molly M

    2017-10-15

    Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6±5.9µm and a total pore surface area of 7.72±1.7m 2 ·g -1 . The electrical conductivity, based on I-V curves, was measured to be 140µS·cm -1 with a reduced, but stable conductivity of 6.1µS·cm -1 after 28days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold

  9. Establishment of a bilateral femoral large segmental bone defect mouse model potentially applicable to basic research in bone tissue engineering.

    PubMed

    Xing, Junchao; Jin, Huiyong; Hou, Tianyong; Chang, Zhengqi; Luo, Fei; Wang, Pinpin; Li, Zhiqiang; Xie, Zhao; Xu, Jianzhong

    2014-12-01

    To understand the cellular mechanism underlying bone defect healing in the context of tissue engineering, a reliable, reproducible, and standardized load-bearing large segmental bone defect model in small animals is indispensable. The aim of this study was to establish and evaluate a bilateral femoral defect model in mice. Donor mouse bone marrow mesenchymal stem cells (mBMSCs) were obtained from six mice (FVB/N) and incorporated into partially demineralized bone matrix scaffolds to construct tissue-engineered bones. In total, 36 GFP(+) mice were used for modeling. Titanium fixation plates with locking steel wires were attached to the femurs for stabilization, and 2-mm-long segmental bone defects were created in the bilateral femoral midshafts. The defects in the left and right femurs were transplanted with tissue-engineered bones and control scaffolds, respectively. The healing process was monitored by x-ray radiography, microcomputed tomography, and histology. The capacity of the transplanted mBMSCs to recruit host CD31(+) cells was investigated by immunofluorescence and real-time polymerase chain reaction. Postoperatively, no complication was observed, except that two mice died of unknown causes. Stable fixation of femurs and implants with full load bearing was achieved in all animals. The process of bone defect repair was significantly accelerated due to the introduction of mBMSCs. Moreover, the transplanted mBMSCs attracted more host CD31(+) endothelial progenitors into the grafts. The present study established a feasible, reproducible, and clinically relevant bilateral femoral large segmental bone defect mouse model. This model is potentially suitable for basic research in the field of bone tissue engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. 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

  11. 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.

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

    PubMed

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

    2003-02-01

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

  14. 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.

  15. 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

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

    PubMed

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

    2017-11-01

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

  17. Detailed Analysis of the Structural Changes of Bone Matrix During the Demineralization Process Using Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Timchenko, E. V.; Zherdeva, L. A.; Timchenko, P. E.; Volova, L. T.; Ponomareva, U. V.

    The results of experimental research of human cortical bone tissue depending on demineralization time were represented using Raman spectroscopy. Depending on demineralization time the ratio of the mineral (РO43- and CO32-) and organic components (amide I) of bone tissue, as well as changes in the spectral regions responsible for the structural integrity of the collagen fibers in bone tissue (1200-1460 cm-1 and 2880-3000 cm-1) were investigated. The observed changes show a decrease in mineral components: thus, the value of Raman band intensity at 956 and 1069 cm-1 for 5 minutes demineralization is 68.5 and 77.3%, for 20 minutes - 55.1 and 61.1%, for 120 minutes - 32.8 and 37% from Raman intensity values of not demineralized tissue objects respectively.

  18. Tissue-Level Mechanical Properties of Bone Contributing to Fracture Risk.

    PubMed

    Nyman, Jeffry S; Granke, Mathilde; Singleton, Robert C; Pharr, George M

    2016-08-01

    Tissue-level mechanical properties characterize mechanical behavior independently of microscopic porosity. Specifically, quasi-static nanoindentation provides measurements of modulus (stiffness) and hardness (resistance to yielding) of tissue at the length scale of the lamella, while dynamic nanoindentation assesses time-dependent behavior in the form of storage modulus (stiffness), loss modulus (dampening), and loss factor (ratio of the two). While these properties are useful in establishing how a gene, signaling pathway, or disease of interest affects bone tissue, they generally do not vary with aging after skeletal maturation or with osteoporosis. Heterogeneity in tissue-level mechanical properties or in compositional properties may contribute to fracture risk, but a consensus on whether the contribution is negative or positive has not emerged. In vivo indentation of bone tissue is now possible, and the mechanical resistance to microindentation has the potential for improving fracture risk assessment, though determinants are currently unknown.

  19. Tissue-level Mechanical Properties of Bone Contributing to Fracture Risk

    PubMed Central

    Nyman, Jeffry S.; Granke, Mathilde; Singleton, Robert C.; Pharr, George M.

    2016-01-01

    Tissue-level mechanical properties characterize mechanical behavior independently of microscopic porosity. Specifically, quasi-static nanoindentation provides measurements of modulus (stiffness) and hardness (resistance to yielding) of tissue at the length scale of the lamella, while dynamic nanoindentation assesses time-dependent behavior in the form of storage modulus (stiffness), loss modulus (dampening), and loss factor (ratio of the two). While these properties are useful in establishing how a gene, signaling pathway, or disease of interest affects bone tissue, they generally do not vary with aging after skeletal maturation or with osteoporosis. Heterogeneity in tissue-level mechanical properties or in compositional properties may contribute to fracture risk, but a consensus on whether the contribution is negative or positive has not emerged. In vivo indentation of bone tissue is now possible, and the mechanical resistance to microindentation has the potential for improving fracture risk assessment, though determinants are currently unknown. PMID:27263108

  20. 3D-Printed Bioactive Ca3SiO5 Bone Cement Scaffolds with Nano Surface Structure for Bone Regeneration.

    PubMed

    Yang, Chen; Wang, Xiaoya; Ma, Bing; Zhu, Haibo; Huan, Zhiguang; Ma, Nan; Wu, Chengtie; Chang, Jiang

    2017-02-22

    Silicate bioactive materials have been widely studied for bone regeneration because of their eminent physicochemical properties and outstanding osteogenic bioactivity, and different methods have been developed to prepare porous silicate bioactive ceramics scaffolds for bone-tissue engineering applications. Among all of these methods, the 3D-printing technique is obviously the most efficient way to control the porous structure. However, 3D-printed bioceramic porous scaffolds need high-temperature sintering, which will cause volume shrinkage and reduce the controllability of the pore structure accuracy. Unlike silicate bioceramic, bioactive silicate cements such as tricalcium silicate (Ca 3 SiO 5 and C 3 S) can be self-set in water to obtain high mechanical strength under mild conditions. Another advantage of using C 3 S to prepare 3D scaffolds is the possibility of simultaneous drug loading. Herein, we, for the first time, demonstrated successful preparation of uniform 3D-printed C 3 S bone cement scaffolds with controllable 3D structure at room temperature. The scaffolds were loaded with two model drugs and showed a loading location controllable drug-release profile. In addition, we developed a surface modification process to create controllable nanotopography on the surface of pore wall of the scaffolds, which showed activity to enhance rat bone-marrow stem cells (rBMSCs) attachment, spreading, and ALP activities. The in vivo experiments revealed that the 3D-printed C 3 S bone cement scaffolds with nanoneedle-structured surfaces significantly improved bone regeneration, as compared to pure C 3 S bone cement scaffolds, suggesting that 3D-printed C 3 S bone cement scaffolds with controllable nanotopography surface are bioactive implantable biomaterials for bone repair.

  1. 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.

  2. Quantitative polarized Raman spectroscopy in highly turbid bone tissue.

    PubMed

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

    2010-01-01

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

  3. 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. © 2016 Wiley Periodicals, Inc.

  4. Mechanical and structural properties of bone in non-critical and critical healing in rat.

    PubMed

    Hoerth, Rebecca M; Seidt, Britta M; Shah, Miheer; Schwarz, Carolin; Willie, Bettina M; Duda, Georg N; Fratzl, Peter; Wagermaier, Wolfgang

    2014-09-01

    A fracture in bone results in a dramatic change of mechanical loading conditions at the site of injury. Usually, bone injuries heal normally but with increasing fracture gaps, healing is retarded, eventually leading to non-unions. The clinical situation of these two processes with different outcomes is well described. However, the exact relation between the mechanical environment and characteristics of the tissues at all levels of structural hierarchy remains unclear. Here we studied the differences in material formation of non-critical (1mm) and critical (5mm gap) healing. We employed a rat osteotomy model to explore bone material structure depending upon the different mechanical conditions. In both cases, primary bone formation was followed by secondary bone deposition with mineral particle sizes changing from on average short and thick to long and thin particles. Bony bridging occurred at first in the endosteal callus and the nanostructure and microstructure developed towards cortical ordered material organization. In contrast, in critical healing, instead of bridging, a marrow cavity closure was formed endosteal, exhibiting tissue structure oriented along the curvature and a periosteal callus with less mature material structure. The two healing processes separated between 4 and 6 weeks post-osteotomy. The outcome of healing was determined by the varied geometrical conditions in critical and non-critical healing, inducing completely different mechanical situations. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Boatman, Elizabeth Marie

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

  6. Phylogenetic, functional, and structural components of variation in bone growth rate of amniotes.

    PubMed

    Cubo, Jorge; Legendre, Pierre; de Ricqlès, Armand; Montes, Laëtitia; de Margerie, Emmanuel; Castanet, Jacques; Desdevises, Yves

    2008-01-01

    The biological features observed in every living organism are the outcome of three sets of factors: historical (inherited by homology), functional (biological adaptation), and structural (properties inherent to the materials with which organs are constructed, and the morphogenetic rules by which they grow). Integrating them should bring satisfactory causal explanations of empirical data. However, little progress has been accomplished in practice toward this goal, because a methodologically efficient tool was lacking. Here we use a new statistical method of variation partitioning to analyze bone growth in amniotes. (1) Historical component. The variation of bone growth rates contains a significant phylogenetic signal, suggesting that the observed patterns are partly the outcome of shared ancestry. (2) Functional causation. High growth rates, although energy costly, may be adaptive (i.e., they may increase survival rates) in taxa showing short growth periods (e.g., birds). In ectothermic amniotes, low resting metabolic rates may limit the maximum possible growth rates. (3) Structural constraint. Whereas soft tissues grow through a multiplicative process, growth of mineralized tissues is accretionary (additive, i.e., mineralization fronts occur only at free surfaces). Bone growth of many amniotes partially circumvents this constraint: it is achieved not only at the external surface of the bone shaft, but also within cavities included in the bone cortex as it grows centrifugally. Our approach contributes to the unification of historicism, functionalism, and structuralism toward a more integrated evolutionary biology.

  7. Qualitative and quantitative observations of bone tissue reactions to anodised implants.

    PubMed

    Sul, Young-Taeg; Johansson, Carina B; Röser, Kerstin; Albrektsson, Tomas

    2002-04-01

    Research projects focusing on biomaterials related factors; the bulk implant material, the macro-design of the implant and the microsurface roughness are routinely being conducted at our laboratories. In this study, we have investigated the bone tissue reactions to turned commercially pure (c.p.) titanium implants with various thicknesses of the oxide films after 6 weeks of insertion in rabbit bone. The control c.p. titanium implants had an oxide thickness of 17-200 nm while the test implants revealed an oxide thickness between 600 and 1000 nm. Routine histological investigations of the tissue reactions around the implants and enzyme histochemical detections of alkaline and acid phosphatase activities demonstrated similar findings around both the control and test implants. In general, the histomorphometrical parameters (bone to implant contact and newly formed bone) revealed significant quantitative differences between the control and test implants. The test implants demonstrated a greater bone response histomorphometrically than control implants and the osteoconductivity was more pronounced around the test implant surfaces. The parameters that differed between the implant surfaces, i.e. the oxide thickness, the pore size distribution, the porosity and the crystallinity of the surface oxides may represent factors that have an influence on the histomorphometrical results indicated by a stronger bone tissue response to the test implant surfaces, with an oxide thickness of more than 600 nm.

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

    PubMed

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

    2016-11-22

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

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue Engineering.

    PubMed

    Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Marimuthu, Thashree; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-11-21

    Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive manner. The success of bioengineered injectable tissue modified delivery systems depends significantly on their chemical, physical and biological properties. Irrespective of shape and defect geometry, injectable therapy has an unparalleled advantage in which intricate therapy sites can be effortlessly targeted with minimally invasive procedures. Using material testing, it was found that properties of stimuli-responsive hydrogel systems enhance cellular responses and cell distribution at any site prior to the transitional phase leading to gelation. The substantially hydrated nature allows significant simulation of the extracellular matrix (ECM), due to its similar structural properties. Significant current research strategies have been identified and reported to date by various institutions, with particular attention to thermo-responsive hydrogel delivery systems, and their pertinent focus for bone tissue engineering. Research on future perspective studies which have been proposed for evaluation, have also been reported in this review, directing considerable attention to the modification of delivering natural and synthetic polymers, to improve their biocompatibility and mechanical properties.

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

    PubMed

    Hillier, Maria L; Bell, Lynne S

    2007-03-01

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

  13. Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing.

    PubMed

    Cunniffe, Gráinne M; Vinardell, Tatiana; Murphy, J Mary; Thompson, Emmet M; Matsiko, Amos; O'Brien, Fergal J; Kelly, Daniel J

    2015-09-01

    Clinical translation of tissue engineered therapeutics is hampered by the significant logistical and regulatory challenges associated with such products, prompting increased interest in the use of decellularized extracellular matrix (ECM) to enhance endogenous regeneration. Most bones develop and heal by endochondral ossification, the replacement of a hypertrophic cartilaginous intermediary with bone. The hypothesis of this study is that a porous scaffold derived from decellularized tissue engineered hypertrophic cartilage will retain the necessary signals to instruct host cells to accelerate endogenous bone regeneration. Cartilage tissue (CT) and hypertrophic cartilage tissue (HT) were engineered using human bone marrow derived mesenchymal stem cells, decellularized and the remaining ECM was freeze-dried to generate porous scaffolds. When implanted subcutaneously in nude mice, only the decellularized HT-derived scaffolds were found to induce vascularization and de novo mineral accumulation. Furthermore, when implanted into critically-sized femoral defects, full bridging was observed in half of the defects treated with HT scaffolds, while no evidence of such bridging was found in empty controls. Host cells which had migrated throughout the scaffold were capable of producing new bone tissue, in contrast to fibrous tissue formation within empty controls. These results demonstrate the capacity of decellularized engineered tissues as 'off-the-shelf' implants to promote tissue regeneration. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Is the bone tissue of ring-billed gulls breeding in a pollution hotspot in the St. Lawrence River, Canada, impacted by halogenated flame retardant exposure?

    PubMed

    Plourde, Stéphanie Pellerin; Moreau, Robert; Letcher, Robert J; Verreault, Jonathan

    2013-11-01

    Bone metabolism is a tightly regulated process that controls bone remodeling and repair in addition to maintaining circulating calcium and phosphate levels. It has been shown that certain organohalogen contaminants may adversely impact bone tissue metabolism and structure in wildlife species. However, exceedingly few studies have addressed the bone-related effects of organohalogen exposure in birds. The objective of the present study was to investigate the associations between markers of bone metabolism and structural integrity, and concentrations of established and current-use halogenated flame retardants (FRs) in ring-billed gulls (Larus delawarensis) nesting in a known FR hotspot area in the St. Lawrence River (Montreal, Canada). Bone metabolism was assessed using plasma calcium and inorganic phosphate levels, and alkaline phophatase activity, while bone (tarsus; trabecular and cortical sections) structure quality was examined using the percentage of bone tissue comprised in the total bone volume (Bv/Tv) and bone mineral density (BMD). Bv/Tv and BMD of the tarsus tended (not significant) to be positively associated with circulating calcium levels in male ring-billed gulls. Moreover, concentrations of FRs in male bird liver (brominated diphenyl ether (BDE)-154, -183, -201, and -209) and plasma (BDE-209) were negatively correlated with trabecular and cortical BMD of the tarsus. These correlative associations may suggest light demineralization of bone tissue associated with FR exposure in male ring-billed gulls. Present findings provide some evidence that bone (tarsus) metabolism and mineral composition may be impacted in high FR-exposed (mainly to PBDEs) ring-billed gulls breeding in the highly urbanized Montreal region. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. [Tissue engineering with mesenchymal stem cells for cartilage and bone regeneration].

    PubMed

    Schaefer, D J; Klemt, C; Zhang, X H; Stark, G B

    2000-09-01

    Tissue engineering offers the possibility to fabricate living substitutes for tissues and organs by combining histogenic cells and biocompatible carrier materials. Pluripotent mesenchymal stem cells are isolated and subcultured ex vivo and then their histogenic differentiation is induced by external factors. The fabrication of bone and cartilage constructs, their combinations and gene therapeutic approaches are demonstrated. Advantages and disadvantages of these methods are described by in vitro and in vitro testing. The proof of histotypical function after implantation in vivo is essential. The use of autologous cells and tissue engineering methods offers the possibility to overcome the disadvantages of classical tissue reconstruction--donor site morbidity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Furthermore, tissue engineering widens the spectrum of surgical indications in bone and cartilage reconstruction.

  16. Biomimetic composite coating on rapid prototyped scaffolds for bone tissue engineering.

    PubMed

    Arafat, M Tarik; Lam, Christopher X F; Ekaputra, Andrew K; Wong, Siew Yee; Li, Xu; Gibson, Ian

    2011-02-01

    The objective of this present study was to improve the functional performance of rapid prototyped scaffolds for bone tissue engineering through biomimetic composite coating. Rapid prototyped poly(ε-caprolactone)/tri-calcium phosphate (PCL/TCP) scaffolds were fabricated using the screw extrusion system (SES). The fabricated PCL/TCP scaffolds were coated with a carbonated hydroxyapatite (CHA)-gelatin composite via biomimetic co-precipitation. The structure of the prepared CHA-gelatin composite coating was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Compressive mechanical testing revealed that the coating process did not have any detrimental effect on the mechanical properties of the scaffolds. The cell-scaffold interaction was studied by culturing porcine bone marrow stromal cells (BMSCs) on the scaffolds and assessing the proliferation and bone-related gene and protein expression capabilities of the cells. Confocal laser microscopy and SEM images of the cell-scaffold constructs showed a uniformly distributed cell sheet and accumulation of extracellular matrix in the interior of CHA-gelatin composite-coated PCL/TCP scaffolds. The proliferation rate of BMSCs on CHA-gelatin composite-coated PCL/TCP scaffolds was about 2.3 and 1.7 times higher than that on PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds, respectively, by day 10. Furthermore, reverse transcription polymerase chain reaction and Western blot analysis revealed that CHA-gelatin composite-coated PCL/TCP scaffolds stimulate osteogenic differentiation of BMSCs the most, compared with PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds. These results demonstrate that CHA-gelatin composite-coated rapid prototyped PCL/TCP scaffolds are promising for bone tissue engineering. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. Cell culture-based tissue engineering as an alternative to bone grafts in implant dentistry: a literature review.

    PubMed

    Boeckel, Daniel Gonçalves; Shinkai, Rosemary Sadami Arai; Grossi, Márcio Lima; Teixeira, Eduardo Rolim

    2012-09-01

    Several biomaterials and techniques for bone grafting have been described in the literature for atresic bone tissue replacement caused by edentulism, surgical resectioning, and traumas. A new technique involves tissue engineering, a promising option to replace bone tissue and solve problems associated with morbidity of autogenous grafting. This literature review aims to describe tissue-engineering techniques using ex vivo cell culture as an alternative to repair bone maxillary atresias and discuss the concepts and potentials of bone regeneration through cell culture techniques as an option for restorative maxillofacial surgery.

  18. Synergistic effect of scaffold composition and dynamic culturing environment in multilayered systems for bone tissue engineering.

    PubMed

    Rodrigues, Márcia T; Martins, Albino; Dias, Isabel R; Viegas, Carlos A; Neves, Nuno M; Gomes, Manuela E; Reis, Rui L

    2012-11-01

    Bone extracellular matrix (ECM) is composed of mineralized collagen fibrils which support biological apatite nucleation that participates in bone outstanding properties. Understanding and mimicking bone morphological and physiological parameters at a biological scale is a major challenge in tissue engineering scaffolding. Using emergent (nano)technologies scaffold designing may be critically improved, enabling highly functional tissue substitutes for bone applications. This study aims to develop novel biodegradable composite scaffolds of tricalcium phosphate (TCPs) and electrospun nanofibers of poly(ϵ-caprolactone) (PCL), combining TCPs osteoconductivity with PCL biocompatibility and elasticity, mimicking bone structure and composition. We hypothesized that scaffolds with such structure/composition would stimulate the proliferation and differentiation of bone marrow stromal cells (BMSCs) towards the osteogenic phenotype. Composite scaffolds, developed by electrospining using consecutive stacked layers of PCL and TCPs, were characterized by FTIR spectroscopy, X-Ray diffraction and scanning electronic microscopy. Cellular behavior was assessed in goat BMSCs seeded onto composite scaffolds and cultured in static or dynamic conditions, using basal or osteogenic media during 7, 14 or 21 days. Cellular proliferation was quantified and osteogenic differentiation confirmed by alkaline phosphatase activity, alizarin red staining and immunocytochemistry for osteocalcin and collagen I. Results suggest that PCL-TCP scaffolds provide a 3D support for gBMSCs proliferation and osteogenic differentiation with production of ECM. TCPs positively stimulate the osteogenic process, especially under dynamic conditions, where PCL-TCP scaffolds are sufficient to promote osteogenic differentiation even in basal medium conditions. The enhancement of the osteogenic potential in dynamic conditions evidences the synergistic effect of scaffold composition and dynamic stimulation in g

  19. Cryogenic 3D printing for producing hierarchical porous and rhBMP-2-loaded Ca-P/PLLA nanocomposite scaffolds for bone tissue engineering.

    PubMed

    Wang, Chong; Zhao, Qilong; Wang, Min

    2017-06-07

    The performance of bone tissue engineering scaffolds can be assessed through cell responses to scaffolds, including cell attachment, infiltration, morphogenesis, proliferation, differentiation, etc, which are determined or heavily influenced by the composition, structure, mechanical properties, and biological properties (e.g. osteoconductivity and osteoinductivity) of scaffolds. Although some promising 3D printing techniques such as fused deposition modeling and selective laser sintering could be employed to produce biodegradable bone tissue engineering scaffolds with customized shapes and tailored interconnected pores, effective methods for fabricating scaffolds with well-designed hierarchical porous structure (both interconnected macropores and surface micropores) and tunable osteoconductivity/osteoinductivity still need to be developed. In this investigation, a novel cryogenic 3D printing technique was investigated and developed for producing hierarchical porous and recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate (Ca-P) nanoparticle/poly(L-lactic acid) nanocomposite scaffolds, in which the Ca-P nanoparticle-incorporated scaffold layer and rhBMP-2-encapsulated scaffold layer were deposited alternatingly using different types of emulsions as printing inks. The mechanical properties of the as-printed scaffolds were comparable to those of human cancellous bone. Sustained releases of Ca 2+ ions and rhBMP-2 were achieved and the biological activity of rhBMP-2 was well-preserved. Scaffolds with a desirable hierarchical porous structure and dual delivery of Ca 2+ ions and rhBMP-2 exhibited superior performance in directing the behaviors of human bone marrow-derived mesenchymal stem cells and caused improved cell viability, attachment, proliferation, and osteogenic differentiation, which has suggested their great potential for bone tissue engineering.

  20. 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.

  1. 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

  2. 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.

  3. 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

    2018-01-01

    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. © 2017 Wiley Periodicals, Inc.

  4. Fabrication and characterization of biomimetic collagen-apatite scaffolds with tunable structures for bone tissue engineering.

    PubMed

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

    2013-07-01

    The objective of the current study is to prepare a biomimetic collagen-apatite 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 then 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 the range 0-54wt.% 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, the 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. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing

    PubMed Central

    Wang, Xin; Friis, Thor E.; Masci, Paul P.; Crawford, Ross W.; Liao, Wenbo; Xiao, Yin

    2016-01-01

    The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing. PMID:27767056

  6. Purification processes of xenogeneic bone substitutes and their impact on tissue reactions and regeneration.

    PubMed

    Perić Kačarević, Zeljka; Kavehei, Faraz; Houshmand, Alireza; Franke, Jörg; Smeets, Ralf; Rimashevskiy, Denis; Wenisch, Sabine; Schnettler, Reinhard; Jung, Ole; Barbeck, Mike

    2018-04-01

    Xenogeneic bone substitute materials are widely used in oral implantology. Prior to their clinical use, purification of the former bone tissue has to be conducted to ensure the removal of immunogenic components and pathogens. Different physicochemical methods are applied for purification of the donor tissue, and temperature treatment is one of these methods. Differences in these methods and especially the application of different temperatures for purification may lead to different material characteristics, which may influence the tissue reactions to these materials and the related (bone) healing process. However, little is known about the different material characteristics and their influences on the healing process. Thus, the aim of this mini-review is to summarize the preparation processes and the related material characteristics, safety aspects, tissue reactions, resorbability and preclinical and clinical data of two widely used xenogeneic bone substitutes that mainly differ in the temperature treatment: sintered (cerabone ® ) and non-sintered (Bio-Oss ® ) bovine-bone materials. Based on the summarized data from the literature, a connection between the material-induced tissue reactions and the consequences for the healing processes are presented with the aim of translation into their clinical application.

  7. 3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering.

    PubMed

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

    2017-04-01

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

  8. Two Distinct Processes of Bone-like Tissue Formation by Dental Pulp Cells after Tooth Transplantation

    PubMed Central

    Yukita, Akira; Yoshiba, Kunihiko; Yoshiba, Nagako; Takahashi, Masafumi; Nakamura, Hiroaki

    2012-01-01

    Dental pulp is involved in the formation of bone-like tissue in response to external stimuli. However, the origin of osteoblast-like cells constructing this tissue and the mechanism of their induction remain unknown. We therefore evaluated pulp mineralization induced by transplantation of a green fluorescent protein (GFP)–labeled tooth into a GFP-negative hypodermis of host rats. Five days after the transplantation, the upper pulp cavity became necrotic; however, cell-rich hard tissue was observed adjacent to dentin at the root apex. At 10 days, woven bone-like tissue was formed apart from the dentin in the upper pulp. After 20 days, these hard tissues expanded and became histologically similar to bone. GFP immunoreactivity was detected in the hard tissue-forming cells within the root apex as well as in the upper pulp. Furthermore, immunohistochemical observation of α–smooth muscle actin, a marker for undifferentiated cells, showed a positive reaction in cells surrounding this bone-like tissue within the upper pulp but not in those within the root apex. Immunoreactivities of Smad4, Runx2, and Osterix were detected in the hard tissue-forming cells within both areas. These results collectively suggest that the dental pulp contains various types of osteoblast progenitors and that these cells might thus induce bone-like tissue in severely injured pulp. PMID:22899860

  9. 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.

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2016-04-05

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

  12. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    NASA Astrophysics Data System (ADS)

    Shrivastava, Pragya; Dalai, Sridhar; Sudera, Prerna; Sivam, Santosh Param; Vijayalakshmi, S.; Sharma, Pratibha

    2013-02-01

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO2 70 mol%, CaO 26 mol % and P2O5 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  13. Deletion of Adseverin in Osteoclasts Affects Cell Structure But Not Bone Metabolism.

    PubMed

    Cao, Yixuan; Wang, Yongqiang; Sprangers, Sara; Picavet, Daisy I; Glogauer, Michael; McCulloch, Christopher A; Everts, Vincent

    2017-08-01

    Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and adseverin null mice, as measured by dual-energy X-ray absorptiometry, there were no differences of bone mineral content or bone mineral density, indicating no change of bone metabolism. In tibiae, TRAcP + osteoclasts were formed in comparable numbers in adseverin null and wild-type mice. Ultrastructural analysis showed normal and similar abundance of ruffled borders, sealing zones, and mitochondria, and with no difference of osteoclast nuclear numbers. In contrast, analyses of long bone showed that in the absence of adseverin osteoclasts were smaller (120 ± 13 vs. 274 ± 19 µm 2 ; p < 0.05), as were nuclear size and the surface area of cytoplasm. The nuclei of adseverin null osteoclasts exhibited more heterochromatin (31 ± 3%) than wild-type cells (8 ± 1%), suggesting that adseverin affects cell differentiation. The data indicate that in healthy, developing tissues, adseverin contributes to the regulation of osteoclast structure but not to bone metabolism in vivo.

  14. Hierarchical Structure and Mechanical Improvement of an n-HA/GCO-PU Composite Scaffold for Bone Regeneration.

    PubMed

    Li, Limei; Zuo, Yi; Zou, Qin; Yang, Boyuan; Lin, Lili; Li, Jidong; Li, Yubao

    2015-10-14

    To improve the mechanical properties of bone tissue and achieve the desired bone tissue regeneration for orthopedic surgery, newly designed hydroxyapatite/polyurethane (HA/PU) porous scaffolds were developed via in situ polymerization. The results showed that the molecular modification of PU soft segments by glyceride of castor oil (GCO) can increase the scaffold compressive strength by 48% and the elastic modulus by 96%. When nano-HA (n-HA) particles were incorporated into the GCO-PU matrix, the compressive strength and elastic modulus further increased by 49 and 74%, from 2.91 to 4.34 MPa and from 95 to 165.36 MPa, respectively. The n-HA particles with fine dispersity not only improved the interface bonding with the GCO-PU matrix but also provided effective bioactivity for bonding with bone tissue. The hierarchical structure and mechanical quality of the n-HA/GCO-PU composite scaffold were determined to be appropriate for the growth of cells and the regeneration of bony tissues, demonstrating promising prospects for bone repair and regeneration.

  15. Bone tissue formation in extraction sockets from sites with advanced periodontal disease: a histomorphometric study in humans.

    PubMed

    Ahn, Jae-Jin; Shin, Hong-In

    2008-01-01

    To investigate postextraction bone formation over time in both diseased and healthy sockets. Core specimens of healing tissues following tooth extraction were obtained at the time of implant placement in patients treated between October 2005 and December 2007. A disease group and a control group were classified according to socket examination at the time of extraction. The biopsy specimens were analyzed histomorphometrically to measure the dimensional changes among 3 tissue types: epithelial layer, connective tissue area, and new bone tissue area. Fifty-five specimens from sites of previously advanced periodontal disease from 45 patients were included in the disease group. Another 12 specimens of previously healthy extraction sockets were collected from 12 different patients as a control. The postextraction period of the disease group varied from 2 to 42 weeks. In the disease group, connective tissue occupied most of the socket during the first 4 weeks. New bone area progressively replaced the connective tissue area after the first 4 weeks. The area proportion of new bone tissue exceeded that of connective tissue by 14 weeks. After 20 weeks, most extraction sockets in the disease group demonstrated continuous new bone formation. The control group exhibited almost complete socket healing after 10 weeks, with no more new bone formation after 20 weeks. Osseous regeneration in the diseased sockets developed more slowly than in the disease-free sockets. After 16 weeks, new bone area exceeded 50% of the total newly regenerated tissue in the sockets with severe periodontal destruction. In the control group, after 8 weeks, new bone area exceeded 50% of the total tissue.

  16. Fourth near-infrared optical window for assessment of bone and other tissues

    NASA Astrophysics Data System (ADS)

    Sordillo, Diana C.; Sordillo, Laura A.; Sordillo, Peter P.; Alfano, Robert R.

    2016-02-01

    Recently, additional near-infrared (NIR) optical windows beyond the conventional first therapeutic window have been utilized for deep tissue imaging through scattering media. Biomedical applications using a second optical window (1100 to 1300 nm) and a third (1600 to 1870 nm) are emerging. A fourth window (2100 to 2300 nm) has been largely ignored due to high water absorption and a lack of high sensitivity imaging detectors and ultrafast laser sources. In this study, optical properties of bone in this fourth NIR optical window, were investigated. Results were compared to those seen at the first, second and third windows, and are consistent with our previous work on malignant and benign breast and prostate tissues. Bone and malignant tissues showed highest uptake in the third and fourth windows. As collagen is a major chromophore with prominent spectral peaks between 2100 and 2300 nm, it may be that the fourth optical window is particularly useful for studying tissues with a higher collagen content, such as bone or malignant tumors.

  17. Leptin: a potential mediator for protective effects of fat mass on bone tissue.

    PubMed

    Thomas, Thierry

    2003-02-01

    Body weight is among the most powerful predictors of bone status, and adipose tissue plays a substantial role in weight-related protective effects on bone. An understanding of the mechanisms underlying the relation between adipose tissue and bone may open up new perspectives for treatment. Leptin, which is known to regulate appetite and energy expenditures, may also contribute to mediate the effects of fat mass on bone. Although reported data are somewhat conflicting, there is some evidence that leptin may decrease bone formation via a central nervous effect and may stimulate both bone formation and bone resorption via direct peripheral effects on stromal precursor cells. The net result of these central and peripheral effects may depend on serum leptin levels and blood-brain barrier permeability, of which the first increase and the second decrease as obesity develops. Further work is needed to improve our understanding of these effects.

  18. Poly(dopamine) coating to biodegradable polymers for bone tissue engineering.

    PubMed

    Tsai, Wei-Bor; Chen, Wen-Tung; Chien, Hsiu-Wen; Kuo, Wei-Hsuan; Wang, Meng-Jiy

    2014-02-01

    In this study, a technique based on poly(dopamine) deposition to promote cell adhesion was investigated for the application in bone tissue engineering. The adhesion and proliferation of rat osteoblasts were evaluated on poly(dopamine)-coated biodegradable polymer films, such as polycaprolactone, poly(l-lactide) and poly(lactic-co-glycolic acid), which are commonly used biodegradable polymers in tissue engineering. Cell adhesion was significantly increased to a plateau by merely 15 s of dopamine incubation, 2.2-4.0-folds of increase compared to the corresponding untreated substrates. Cell proliferation was also greatly enhanced by poly(dopamine) deposition, indicated by shortened cell doubling time. Mineralization was also increased on the poly(dopamine)-deposited surfaces. The potential of poly(dopamine) deposition in bone tissue engineering is demonstrated in this study.

  19. Tissue Engineering Whole Bones Through Endochondral Ossification: Regenerating the Distal Phalanx.

    PubMed

    Sheehy, Eamon J; Mesallati, Tariq; Kelly, Lara; Vinardell, Tatiana; Buckley, Conor T; Kelly, Daniel J

    2015-01-01

    Novel strategies are urgently required to facilitate regeneration of entire bones lost due to trauma or disease. In this study, we present a novel framework for the regeneration of whole bones by tissue engineering anatomically shaped hypertrophic cartilaginous grafts in vitro that subsequently drive endochondral bone formation in vivo. To realize this, we first fabricated molds from digitized images to generate mesenchymal stem cell-laden alginate hydrogels in the shape of different bones (the temporomandibular joint [TMJ] condyle and the distal phalanx). These constructs could be stimulated in vitro to generate anatomically shaped hypertrophic cartilaginous tissues that had begun to calcify around their periphery. Constructs were then formed into the shape of the distal phalanx to create the hypertrophic precursor of the osseous component of an engineered long bone. A layer of cartilage engineered through self-assembly of chondrocytes served as the articular surface of these constructs. Following chondrogenic priming and subcutaneous implantation, the hypertrophic phase of the engineered phalanx underwent endochondral ossification, leading to the generation of a vascularized bone integrated with a covering layer of stable articular cartilage. Furthermore, spatial bone deposition within the construct could be modulated by altering the architecture of the osseous component before implantation. These findings open up new horizons to whole limb regeneration by recapitulating key aspects of normal bone development.

  20. 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

  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

    Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

    2012-11-01

    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. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

  2. Engineering bone grafts with enhanced bone marrow and native scaffolds.

    PubMed

    Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

    2013-01-01

    The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds. © 2013 S. Karger AG, Basel

  3. 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.

  4. Compact biomedical pulsed signal generator for bone tissue stimulation

    DOEpatents

    Kronberg, James W.

    1993-01-01

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

  5. Early fixation of cobalt-chromium based alloy surgical implants to bone using a tissue-engineering approach.

    PubMed

    Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

    2012-01-01

    To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation.

  6. Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach

    PubMed Central

    Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

    2012-01-01

    To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation. PMID:22754313

  7. Perivascular Stem Cells: A Prospectively Purified Mesenchymal Stem Cell Population for Bone Tissue Engineering

    PubMed Central

    James, Aaron W.; Zara, Janette N.; Zhang, Xinli; Askarinam, Asal; Goyal, Raghav; Chiang, Michael; Yuan, Wei; Chang, Le; Corselli, Mirko; Shen, Jia; Pang, Shen; Stoker, David; Wu, Ben

    2012-01-01

    Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence-activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient-matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel-like molecule 1 (NELL-1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose-derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell-based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL-1 is a candidate growth factor able to induce human PSC osteogenesis. PMID:23197855

  8. The sintered microsphere matrix for bone tissue engineering: in vitro osteoconductivity studies.

    PubMed

    Borden, Mark; Attawia, Mohamed; Laurencin, Cato T

    2002-09-05

    A tissue engineering approach has been used to design three-dimensional synthetic matrices for bone repair. The osteoconductivity and degradation profile of a novel polymeric bone-graft substitute was evaluated in an in vitro setting. Using the copolymer poly(lactide-co-glycolide) [PLAGA], a sintering technique based on microsphere technology was used to fabricate three-dimensional porous scaffolds for bone regeneration. Osteoblasts and fibroblasts were seeded onto a 50:50 PLAGA scaffold. Morphologic evaluation through scanning electron microscopy demonstrated that both cell types attached and spread over the scaffold. Cells migrated through the matrix using cytoplasmic extensions to bridge the structure. Cross-sectional images indicated that cellular proliferation had penetrated into the matrix approximately 700 microm from the surface. Examination of the surfaces of cell/matrix constructs demonstrated that cellular proliferation had encompassed the pores of the matrix by 14 days of cell culture. With the aim of optimizing polymer composition and polymer molecular weight, a degradation study was conducted utilizing the matrix. The results demonstrate that degradation of the sintered matrix is dependent on molecular weight, copolymer ratio, and pore volume. From this data, it was determined that 75:25 PLAGA with an initial molecular weight of 100,000 has an optimal degradation profile. These studies show that the sintered microsphere matrix has an osteoconductive structure capable of functioning as a cellular scaffold with a degradation profile suitable for bone regeneration. Copyright 2002 Wiley Periodicals, Inc.

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

    PubMed

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

    2012-09-01

    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. 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. 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. 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 premenopausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. 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.

  10. Acellular dermal matrix in soft tissue reconstruction prior to bone grafting. A case report.

    PubMed

    Ruiz-Magaz, Vanessa; Hernández-Alfaro, Federico; Díaz-Carandell, Artur; Biosca-Gómez-de-Tejada, María-José

    2010-01-01

    When hard tissue augmentation is scheduled as a part of an oral rehabilitation, prior to the treatment, it is important to assess if the quality of the underlying gingiva at the recipient site can support the bone grafting procedure. The most frequent complication during autologous onlay grafts are wound dehiscences in the recipient site, so the integrity of soft tissues is a basic aspect of successful reconstructive and plastic surgical procedure. Connective tissue grafts can improve the quality and quantity of soft tissue in oral sites where a hard tissue reconstruction is going to take place. However, particularly when large grafts are harvested, the autogenous donor site can present significant postoperative morbidity, such as necrosis of the palate fibromucosa and bone exposition, pain and bleeding. Another important limitation with the use of autogenous grafts is the limited supply of donor connective tissue. If a large site needs to be grafted, more than one surgical procedure may be required. An Acellular Dermal Matrix (ADM) graft has become increasingly popular as a substitute for donor connective tissue, eliminating the disadvantages described for the autogenous donor graft. The amount of tissue harvested is unlimited, so it gives an option for treating patients that have inadequate harvestable tissue or that present a large defect to be treated. The outcome of using ADM as a matrix for soft tissue reconstruction 12 weeks before bone grafting can reduce the risk of exposure and failure of the bone graft.

  11. Development, regulation, metabolism and function of bone marrow adipose tissues.

    PubMed

    Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

    2018-05-01

    Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed Central

    PEELUKHANA, Srikara V.; GOENKA, Shilpi; KIM, Brian; KIM, Jay; BHATTACHARYA, Amit; STRINGER, Keith F.; BANERJEE, Rupak K.

    2015-01-01

    To formulate more accurate guidelines for musculoskeletal disorders (MSD) linked to Hand-Arm Vibration Syndrome (HAVS), delineation of the response of bone tissue under different frequencies and duration of vibration needs elucidation. Rat-tails were vibrated at 125 Hz (9 rats) and 250 Hz (9 rats), at 49 m/s2, for 1D (6 rats), 5D (6 rats) and 20D (6 rats); D=days (4 h/d). Rats in the control group (6 rats for the vibration groups; 2 each for 1D, 5D, and 20D) were left in their cages, without being subjected to any vibration. Structural and biochemical damages were quantified using empty lacunae count and nitrotyrosine signal-intensity, respectively. One-way repeated-measure mixed-model ANOVA at p<0.05 level of significance was used for analysis. In the cortical bone, structural damage quantified through empty lacunae count was significant (p<0.05) at 250 Hz (10.82 ± 0.66) in comparison to the control group (7.41 ± 0.76). The biochemical damage was significant (p<0.05) at both the 125 Hz and 250 Hz vibration frequencies. The structural damage was significant (p<0.05) at 5D for cortical bone while the trabecular bone showed significant (p<0.05) damage at 20D time point. Further, the biochemical damage increased with increase in the duration of vibration with a significant (p<0.05) damage observed at 20D time point and a near significant change (p=0.08) observed at 5D time point. Structural and biochemical changes in bone tissue are dependent upon higher vibration frequencies of 125 Hz, 250 Hz and the duration of vibration (5D, 20D). PMID:25843564

  13. Study of tissue engineered bone nodules by Fourier transform infrared spectroscopy.

    PubMed

    Aydin, Halil Murat; Hu, Bin; Suso, Josep Sulé; El Haj, Alicia; Yang, Ying

    2011-02-21

    The key criteria for assessing the success of bone tissue engineering are the quality and quantity of the produced minerals within the cultured constructs. The accumulation of calcium ions and inorganic phosphates in culture medium serves as nucleating agents for the formation of hydroxyapatite, which is the main inorganic component of bone. Bone nodule formation is one of the hallmarks of mineralization in such cell cultures. In this study, we developed a new two-step procedure to accelerate bone formation in which mouse bone cell aggregates were produced first on various chemically treated non-adhesive substrates. After this step, the bone cells' growth and mineralization were followed in conventional culture plates. The number and size of cell aggregates were studied with light microscopy. The minerals' formation in the form of nodules produced by the cell aggregates and the bone crystal quality were studied with Fourier Transform Infrared (FTIR) spectroscopy. The FTIR spectra of the ash specimens (mineral phase only) from thermal gravimetric analysis (TGA) provided valuable information of the quality of the minerals. The υ(4) PO(4) region (550-650 cm(-1)), which reveals apatitic and non-apatitic HPO(4) or PO(4) environments, and phosphate region (910-1180 cm(-1)) were examined for the minerals produced in the form of nodules. The peak position and intensity of the spectra demonstrate that the quality of the bone produced by cell aggregates, especially from the bigger ones, which were formed on Plunoric treated substrates, exhibit a composition more similar to that of native bone. This work establishes a new protocol for high quality bone formation and characterization, with the potential to be applied to bone tissue engineering.

  14. 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.

  15. Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

    PubMed

    Suchacki, Karla J; Cawthorn, William P

    2018-01-01

    The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

  16. Assessment of imaging quality in magnified phase CT of human bone tissue at the nanoscale

    NASA Astrophysics Data System (ADS)

    Yu, Boliang; Langer, Max; Pacureanu, Alexandra; Gauthier, Remy; Follet, Helene; Mitton, David; Olivier, Cecile; Cloetens, Peter; Peyrin, Francoise

    2017-10-01

    Bone properties at all length scales have a major impact on the fracture risk in disease such as osteoporosis. However, quantitative 3D data on bone tissue at the cellular scale are still rare. Here we propose to use magnified X-ray phase nano-CT to quantify bone ultra-structure in human bone, on the new setup developed on the beamline ID16A at the ESRF, Grenoble. Obtaining 3D images requires the application of phase retrieval prior to tomographic reconstruction. Phase retrieval is an ill-posed problem for which various approaches have been developed. Since image quality has a strong impact on the further quantification of bone tissue, our aim here is to evaluate different phase retrieval methods for imaging bone samples at the cellular scale. Samples from femurs of female donors were scanned using magnified phase nano-CT at voxel sizes of 120 and 30 nm with an energy of 33 keV. Four CT scans at varying sample-to-detector distances were acquired for each sample. We evaluated three phase retrieval methods adapted to these conditions: Paganin's method at single distance, Paganin's method extended to multiple distances, and the contrast transfer function (CTF) approach for pure phase objects. These methods were used as initialization to an iterative refinement step. Our results based on visual and quantitative assessment show that the use of several distances (as opposed to single one) clearly improves image quality and the two multi-distance phase retrieval methods give similar results. First results on the segmentation of osteocyte lacunae and canaliculi from such images are presented.

  17. Nanocomposites and bone regeneration

    NASA Astrophysics Data System (ADS)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

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

    PubMed

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

    2015-02-01

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

  19. Investigation of Osteoinductive Effects of Different Compositions of Bioactive Glass Nanoparticles for Bone Tissue Engineering.

    PubMed

    Tavakolizadeh, AmirHossein; Ahmadian, Mehdi; Fathi, Mohammad Hossein; Doostmohammadi, Ali; Seyedjafari, Ehsan; Ardeshirylajimi, Abdolreza

    Bioactive glasses (BG) is one of the well-known materials that used as dental and bone implants, for this reason it is always interesting for researchers has been to increase BG efficiency in the bone tissue engineering. The aim of this study was to evaluate the osteoinductivity of BG different composition nanoparticles with SiO2-CaO-P2O5. The 45S, 58S, and 63S compositions were prepared via the sol-gel technique. Characterization techniques such as x-ray diffraction, field emission scanning electron microscopy (FE-SEM), and laser Doppler electrophoresis (LDE) were used. The osteoinductive capacity of prepared nanoparticles was investigated using unrestricted somatic stem cells (USSC). The particle size of the samples with an amorphous structure mainly ranged less than 40 nm. The zeta potential was negative for all compositions in distilled water at pH 7.4. Bioactive glass nanoparticles were shown to support proliferation of USSC, as shown by microculture tetrazolium (MTT) assay. During osteogenic differentiation, significantly highest values of alkaline phosphatase (ALP) activity and biomineralization were observed on 45S BG. Subsequently, these markers were measured in higher amounts in USSC on 58S and 63S BG compared with tissue culture polystyrene. The nanometric particle size, osteoinductivity, and negative zeta potential make this material a possible candidate for bone tissue engineering applications.

  20. Changes in functional activity of bone tissue cells under space flight conditions.

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia; Nesterenko, Olga; Kabitskaya, Olga

    osteoclasts. Among them are typical osteoclasts with 3 to 4 nuclei on a section, as well as the "giant" cells with 5 to 6 nuclei and a highly developed zone 2, in which organelles and structures are concentrated, providing for specific functions (primary and secondary lysosomes, heterophagous vacuoles, fibrous layer and "brush border"). The availability of these functionally active osteoclasts testify to the intensification of resorptive processes in remodelling zones. To confirm the obtained electronmicroscopic findings, the experiments were conducted on albino rats under model microgravity conditions ("tail suspension" method) with the use of radionuclides. The experiments with 3H-glycine demonstrated a lower isotope uptake in the osteogenetic cells compared with the control. The autoradiographic studies employing 3H-thymidine, showed that hind limbs unloading leads to a significant acceleration of osteoclast formation in zones of spongy bone reconstruction. Considering the obtained results, the cell mechanisms of osteoclast - osteoblast remodelling and bone tissue loss under the action of space flight factors are discussed.

  1. Peri-Implant Tissue Findings in Bone Grafted Oral Cancer Patients Compared to non Bone Grafted Patients without Oral Cancer

    PubMed Central

    Agata, Hideki; Sándor, George K.; Haimi, Suvi

    2011-01-01

    ABSTRACT Objectives The aim of this study was to compare microbiological, histological, and mechanical findings from tissues around osseointergrated dental implants in patients who had undergone tumour resection and subsequent bone grafting with non bone grafted patients without a history of oral cancer and to develop an effective tool for the monitoring of the peri-implant tissues. A third aim was to assess and compare the masticatory function of the two patient groups after reconstruction with dental implants. Material and Methods A total of 20 patients were divided into 2 groups. The first group was edentulous and treated with dental implants without the need for bone grafting. The second edentulous group, with a history of oral cancer involving the mandible, received onlay bone grafts with concurrent placement of dental implants. Microbiological, histological, mechanical and biochemical assessment methods, crevicular fluid flow rate, hygiene-index, implant mobility, and the masticatory function were analysed and compared in both patient groups. Results The microbiological examinations showed no evidence of the three most common pathogenic bacteria: Porphyromonas gingivalis, Prevotella intermedius, Actinobacillus actinomycetencomitans. A causal relationship between specific microbes and peri-implant inflammation could not be found. All biopsies in both patient groups revealed early signs of soft tissue peri-implant inflammation. Conclusions The crevicular fluid volume and grade of gingival inflammation around the dental implants were related. Peri-implant tissue findings were similar in the two patient groups despite the history of oral cancer and the need for bone grafting at the time of dental implant placement. PMID:24421999

  2. PCL-HA microscaffolds for in vitro modular bone tissue engineering.

    PubMed

    Totaro, Alessandra; Salerno, Aurelio; Imparato, Giorgia; Domingo, Concepción; Urciuolo, Francesco; Netti, Paolo Antonio

    2017-06-01

    The evolution of microscaffolds and bone-bioactive surfaces is a pivotal point in modular bone tissue engineering. In this study, the design and fabrication of porous polycaprolactone (PCL) microscaffolds functionalized with hydroxyapatite (HA) nanoparticles by means of a bio-safe and versatile thermally-induced phase separation process is reported. The ability of the as-prepared nanocomposite microscaffolds to support the adhesion, growth and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in standard and osteogenic media and using dynamic seeding/culture conditions was investigated. The obtained results demonstrated that the PCL-HA nanocomposite microparticles had an enhanced interaction with hMSCs and induced their osteogenic differentiation, even without the exogenous addition of osteogenic factors. In particular, calcium deposition, alizarin red assay, histological analysis, osteogenic gene expression and collagen I secretion were assessed. The results of these tests demonstrated the formation of bone microtissue precursors after 28 days of dynamic culture. These findings suggest that PCL-HA nanocomposite microparticles represent an excellent platform for in vitro modular bone tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

    PubMed

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

    2013-11-01

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

  4. State of the mineral component of rat bone tissue during hypokinesia and the recovery period

    NASA Technical Reports Server (NTRS)

    Volozhin, A. I.; Stupakov, G. P.; Pavlova, M. N.; Muradov, I. S.

    1980-01-01

    Experiments were conducted on young growing rats. Hypokinesia lasting from 20 to 200 days caused retarded gain in weight and volume of the femur and delayed development of the cortical layer of the diaphysis. In contrast, the density of the cortical layer of the femoral diaphysis increased due to elevation of the mineral saturation of the bone tissue microstructures. Incorporation of Ca into the bone tissue in hypokinesia had a tendency to reduce. Partial normalization of the bone tissue mineral component occurred during a 20 day recovery period following hypokinesia.

  5. Different methods of dentin processing for application in bone tissue engineering: A systematic review.

    PubMed

    Tabatabaei, Fahimeh Sadat; Tatari, Saeed; Samadi, Ramin; Moharamzadeh, Keyvan

    2016-10-01

    Dentin has become an interesting potential biomaterial for tissue engineering of oral hard tissues. It can be used as a scaffold or as a source of growth factors in bone tissue engineering. Different forms of dentin have been studied for their potential use as bone substitutes. Here, we systematically review different methods of dentin preparation and the efficacy of processed dentin in bone tissue engineering. An electronic search was carried out in PubMed and Scopus databases for articles published from 2000 to 2016. Studies on dentin preparation for application in bone tissue engineering were selected. The initial search yielded a total of 1045 articles, of which 37 were finally selected. Review of studies showed that demineralization was the most commonly used dentin preparation process for use in tissue engineering. Dentin extract, dentin particles (tooth ash), freeze-dried dentin, and denatured dentin are others method of dentin preparation. Based on our literature review, we can conclude that preparation procedure and the size and shape of dentin particles play an important role in its osteoinductive and osteoconductive properties. Standardization of these methods is important to draw a conclusion in this regard. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2616-2627, 2016. © 2016 Wiley Periodicals, Inc.

  6. Morphological and ultrastructural comparative analysis of bone tissue after Er:YAG laser and surgical drill osteotomy.

    PubMed

    Panduric, Dragana Gabric; Juric, Ivona Bago; Music, Svetozar; Molčanov, Krešimir; Sušic, Mato; Anic, Ivica

    2014-07-01

    The purpose of this study was to analyze morphological, chemical, and crystallographic changes of bone tissue after osteotomy performed with an erbium:yttrium-aluminium-garnet (Er:YAG) laser and a low speed pilot drill. Bone blocks were prepared from porcine ribs, and on each block, two tunnel preparations were performed using the Er:YAG laser (pulse energy: 1000 mJ, pulse duration: 300 μs, pulse repetition rate: 20 Hz) or the low-speed surgical pilot drill. The morphological changes of the cortical and the spongious surface of the tunnel preparations were analyzed under the field emission scanning electron microscopy (FE-SEM) at low and high resolution. The distribution and the level of chemical elements in the treated surfaces were evaluated by qualitative and semiquantitative energy dispersive x-ray analysis (SEM-EDX). Diffraction x-ray analysis was used to detect any differences and thermally induced modifications of hydroxyapatite crystals. FE-SEM revealed sharp edges of the Er:YAG preparations, with empty intertrabecular spaces and no signs of carbonization. In the drill group, the surface of the preparations was smooth, completely covered with smear layer and microcracks, and with hairy-like irregularities on the edges. SEM-EDX analysis did not reveal any differences in the number of specific chemical elements between the laser and the drill group. There were no thermally induced modifications of hydroxyapatite crystal structure in the bone tissue in either group. The Er:YAG laser ablation did not cause any chemical or crystallographic changes of the bone tissue. Compared with the drill, Er:YAG laser created well-defined edges of the preparations, and cortical bone had no smear layer.

  7. Design and optimization of a novel bio-loom to weave melt-spun absorbable polymers for bone tissue engineering.

    PubMed

    Gilmore, Jordon; Burg, Timothy; Groff, Richard E; Burg, Karen J L

    2017-08-01

    Bone graft procedures are currently among the most common surgical procedures performed worldwide, but due to high risk of complication and lack of viable donor tissue, there exists a need to develop alternatives for bone defect healing. Tissue engineering, for example, combining biocompatible scaffolds with mesenchymal stem cells to achieve new bone growth, is a possible solution. Recent work has highlighted the potential for woven polymer meshes to serve as bone tissue engineering scaffolds; since, scaffolds can be iteratively designed by adjusting weave settings, material types, and mesh parameters. However, there are a number of material and system challenges preventing the implementation of such a tissue engineering strategy. Fiber compliance, tensile strength, brittleness, cross-sectional geometry, and size present specific challenges for using traditional textile weaving methods. In the current work, two potential scaffold materials, melt-spun poly-l-lactide, and poly-l-lactide-co-ε-caprolactone, were investigated. An automated bio-loom was engineered and built to weave these materials. The bio-loom was used to successfully demonstrate the weaving of these difficult-to-handle fiber types into various mesh configurations and material combinations. The dobby-loom design, adapted with an air jet weft placement system, warp tension control system, and automated collection spool, provides minimal damage to the polymer fibers while overcoming the physical constraints presented by the inherent material structure. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1342-1351, 2017. © 2016 Wiley Periodicals, Inc.

  8. Calcium Silicate/Chitosan-Coated Electrospun Poly (Lactic Acid) Fibers for Bone Tissue Engineering.

    PubMed

    Su, Chu-Jung; Tu, Ming-Gene; Wei, Li-Ju; Hsu, Tuan-Ti; Kao, Chia-Tze; Chen, Tsui-Han; Huang, Tsui-Hsien

    2017-05-05

    Electrospinning technology allows fabrication of nano- or microfibrous fibers with inorganic and organic matrix and it is widely applied in bone tissue engineering as it allows precise control over the shapes and structures of the fibers. Natural bone has an ordered composition of organic fibers with dispersion of inorganic apatite among them. In this study, poly (lactic acid) (PLA) mats were fabricated with electrospinning and coated with chitosan (CH)/calcium silicate (CS) mixer. The microstructure, chemical component, and contact angle of CS/CH-PLA composites were analyzed by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. In vitro, various CS/CH-coated PLA mats increased the formation of hydroxyapatite on the specimens' surface when soaked in cell cultured medium. During culture, several biological characteristics of the human mesenchymal stem cells (hMSCs) cultured on CS/CH-PLA groups were promoted as compared to those on pure PLA mat. Increased secretion levels of Collagen I and fibronectin were observed in calcium silicate-powder content. Furthermore, with comparison to PLA mats without CS/CH, CS10 and CS15 mats markedly enhanced the proliferation of hMSCs and their osteogenesis properties, which was characterized by osteogenic-related gene expression. These results clearly demonstrated that the biodegradable and electroactive CS/CH-PLA composite mats are an ideal and suitable candidate for bone tissue engineering.

  9. Role of structural anisotropy of biological tissues in poroelastic wave propagation

    PubMed Central

    Cardoso, Luis; Cowin, Stephen C.

    2011-01-01

    Ultrasound waves have a broad range of clinical applications as a non-destructive testing approach in imaging and in the diagnoses of medical conditions. Generally, biological tissues are modeled as an homogenized equivalent medium with an apparent density through which a single wave propagates. Only the first wave arriving at the ultrasound probe is used for the measurement of the speed of sound. However, the existence of a second wave in tissues such as cancellous bone has been reported and its existence is an unequivocal signature of Biot type poroelastic media. To account for the fact that ultrasound is sensitive to microarchitecture as well as density, a fabric-dependent anisotropic poroelastic ultrasound (PEU) propagation theory was recently developed. Key to this development was the inclusion of the fabric tensor - a quantitative stereological measure of the degree of structural anisotropy of bone - into the linear poroelasticity theory. In the present study, this framework is extended to the propagation of waves in several soft and hard tissues. It was found that collagen fibers in soft tissues and the mineralized matrix in hard tissues are responsible for the anisotropy of the solid tissue constituent through the fabric tensor in the model. PMID:22162897

  10. 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.

  11. 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.

  12. 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

  13. The resistance of cortical bone tissue to failure under cyclic loading is reduced with alendronate.

    PubMed

    Bajaj, Devendra; Geissler, Joseph R; Allen, Matthew R; Burr, David B; Fritton, J C

    2014-07-01

    Bisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0mg/kg/day; alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (-14%; ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×10(3) μm2; p<0.01) and the density of osteocyte lacunae (-20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×10(2) #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. 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.

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

    PubMed

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

    2016-10-21

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

  16. Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow

    PubMed Central

    Kim, Su-Hwan; Kim, Young-Sung; Lee, Su-Yeon; Kim, Kyoung-Hwa; Lee, Yong-Moo; Kim, Won-Kyung

    2011-01-01

    Purpose The aim of this study is to compare the gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow for characterization of dental stem cells. Methods We employed GeneChip analysis to the expression levels of approximately 32,321 kinds of transcripts in 5 samples of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell was sorted by a FACS Vantage Sorter using immunocytochemical staining of the early mesenchymal stem cell surface marker STRO-1 before the microarray analysis. Results We identified 379 up-regulated and 133 down-regulated transcripts in BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up-regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical structure development and anatomical structure morphogenesis gene ontology (GO) terms were over-represented in all three different mesenchymal stem cells and GO terms related to blood vessels, and neurons were over-represented only in DPSCs. Conclusions This study demonstrated the genome-wide gene expression patterns of STRO-1+ mesenchymal stem cells derived from dental tissues and bone marrow. The differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown, and 999 candidate genes were found to be definitely up- or down-regulated. In addition, GOstat analyses of regulated gene products provided over-represented GO classes. These data provide a first step for discovering molecules key to the characteristics of dental stem cells. PMID:21954424

  17. Segmentation of bone and soft tissue regions in digital radiographic images of extremities

    NASA Astrophysics Data System (ADS)

    Pakin, S. Kubilay; Gaborski, Roger S.; Barski, Lori L.; Foos, David H.; Parker, Kevin J.

    2001-07-01

    This paper presents an algorithm for segmentation of computed radiography (CR) images of extremities into bone and soft tissue regions. The algorithm is a region-based one in which the regions are constructed using a growing procedure with two different statistical tests. Following the growing process, tissue classification procedure is employed. The purpose of the classification is to label each region as either bone or soft tissue. This binary classification goal is achieved by using a voting procedure that consists of clustering of regions in each neighborhood system into two classes. The voting procedure provides a crucial compromise between local and global analysis of the image, which is necessary due to strong exposure variations seen on the imaging plate. Also, the existence of regions whose size is large enough such that exposure variations can be observed through them makes it necessary to use overlapping blocks during the classification. After the classification step, resulting bone and soft tissue regions are refined by fitting a 2nd order surface to each tissue, and reevaluating the label of each region according to the distance between the region and surfaces. The performance of the algorithm is tested on a variety of extremity images using manually segmented images as gold standard. The experiments showed that our algorithm provided a bone boundary with an average area overlap of 90% compared to the gold standard.

  18. Evaluating differential nuclear DNA yield rates and osteocyte numbers among human bone tissue types: A synchrotron radiation micro-CT approach.

    PubMed

    Andronowski, Janna M; Mundorff, Amy Z; Pratt, Isaac V; Davoren, Jon M; Cooper, David M L

    2017-05-01

    Molecular human identification has conventionally focused on DNA sampling from dense, weight-bearing cortical bone tissue, typically from femora or tibiae. A comparison of skeletal elements from three contemporary individuals demonstrated that elements with high quantities of cancellous bone yielded nuclear DNA at the highest rates, suggesting that preferentially sampling cortical bone may be suboptimal (Mundorff & Davoren, 2014). Despite these findings, the reason for the differential DNA yields between cortical and cancellous bone tissues remains unknown. The primary goal of this work is to ascertain whether differences in bone microstructure can be used to explain differential nuclear DNA yield among bone tissue types observed by Mundorff and Davoren (2014), with a focus on osteocytes and the three-dimensional (3D) quantification of their associated lacunae. Osteocytes and other bone cells are recognized to house DNA in bone tissue, thus examining the density of their lacunae may explain why nuclear DNA yield rates differ among bone tissue types. Lacunae were visualized and quantified using synchrotron radiation-based micro-Computed Tomographic imaging (SR micro-CT). Volumes of interest (VOIs) from cortical and cancellous bone tissues (n=129) were comparatively analyzed from the three skeletons sampled for Mundorff and Davoren's (2014) study. Analyses tested the primary hypothesis that the abundance and density of osteocytes (inferred from their lacunar spaces) vary between cortical and cancellous bone tissue types. Results demonstrated that osteocyte lacunar abundance and density vary between cortical and cancellous bone tissue types, with cortical bone VOIs containing a higher lacunar abundance and density. We found that the osteocyte lacunar density values are independent of nuclear DNA yield, suggesting an alternative explanation for the higher nuclear DNA yields from bones with greater quantities of cancellous bone tissue. The use of SR micro-CT allowed for

  19. Development of bioactive porous α-TCP/HAp beads for bone tissue engineering.

    PubMed

    Asaoka, Teruo; Ohtake, Shoji; Furukawa, Katsuko S; Tamura, Akito; Ushida, Takashi

    2013-11-01

    Porous beads of bioactive ceramics such as hydroxyapatite (HAp) and tribasic calcium phosphate (TCP) are considered a promising scaffold for cultivating bone cells. To realize this, α-TCP/HAp functionally graded porous beads are fabricated with two main purposes: to maintain the function of the scaffold with sufficient strength up to the growth of new bone, and is absorbed completely after the growth. HAp is a bioactive material that has both high strength and strong tissue-adhesive properties, but is not readily absorbed by the human body. On the contrary, α-TCP is highly bioabsorbable, resulting in a scaffold that is absorbed before it is completely replaced by bone. In this study, we produced porous, bead-shaped carriers as scaffolds for osteoblast culture. To control the solubility in vivo, the fabricated beads contained α-TCP at the center and HAp at the surface. Cell adaptability of these beads for bone tissue engineering was confirmed in vitro. It was found that α-TCP/HAp bead carriers exhibit low toxicity in the initial stages of cell seeding and cell adhesion. The presence of HAp in the composite bead form effectively increased ALP activity. In conclusion, it is suggested that these newly developed α-TCP/HAp beads are a promising tool for bone tissue engineering. Copyright © 2013 Wiley Periodicals, Inc.

  20. Bone morphogenetic protein 2 and decorin expression in old fracture fragments and surrounding tissues.

    PubMed

    Han, X G; Wang, D K; Gao, F; Liu, R H; Bi, Z G

    2015-09-21

    Bone morphogenetic protein 2 (BMP-2) can promote fracture healing. Although the complex role BMP-2 in bone formation is increasingly understood, the role of endogenous BMP-2 in nonunion remains unclear. Decorin (DCN) can promote the formation of bone matrix and calcium deposition to control bone morphogenesis. In this study, tissue composition and expression of BMP-2 and DCN were detected in different parts of old fracture zones to explore inherent anti-fibrotic ability and osteogenesis. Twenty-three patients were selected, including eight cases of delayed union and 15 cases of nonunion. Average duration of delayed union or nonunion was 15 months. Fracture fragments and surrounding tissues, including bone grafts, marrow cavity contents, and sticking scars, were categorically sampled during surgery. Through observation and histological testing, component comparisons were made between fracture fragments and surrounding tissue. The expression levels of DCN and BMP-2 in different tissues were detected by immunohistochemical staining and real-time polymerase chain reaction. The expression of DCN and BMP- 2 in different parts of the nonunion area showed that, compared with bone graft and marrow cavity contents, sticking scars had the highest expression of BMP-2. Compared with the marrow cavity contents and sticking scars, bone grafts had the highest expression of DCN. The low antifibrotic and osteogenic activity of the nonunion area was associated with non-co-expression of BMP-2 and DCN. Therefore, the co-injection of osteogenic factor BMP and DCN into the nonunion area can improve the induction of bone formation and enhance the conversion of the old scar, thereby achieving better nonunion treatment.

  1. Optimizing Biomaterials for Tissue Engineering Human Bone Using Mesenchymal Stem Cells.

    PubMed

    Weinand, Christian; Neville, Craig M; Weinberg, Eli; Tabata, Yasuhiko; Vacanti, Joseph P

    2016-03-01

    Adequate biomaterials for tissue engineering bone and replacement of bone in clinical settings are still being developed. Previously, the combination of mesenchymal stem cells in hydrogels and calcium-based biomaterials in both in vitro and in vivo experiments has shown promising results. However, results may be optimized by careful selection of the material combination. β-Tricalcium phosphate scaffolds were three-dimensionally printed with five different hydrogels: collagen I, gelatin, fibrin glue, alginate, and Pluronic F-127. The scaffolds had eight channels, running throughout the entire scaffold, and macropores. Mesenchymal stem cells (2 × 10) were mixed with each hydrogel, and cell/hydrogel mixes were dispersed onto the corresponding β-tricalcium phosphate/hydrogel scaffold and cultured under dynamic-oscillating conditions for 6 weeks. Specimens were harvested at 1, 2, 4, and 6 weeks and evaluated histologically, radiologically, biomechanically and, at 6 weeks, for expression of bone-specific proteins by reverse-transcriptase polymerase chain reaction. Statistical correlation analysis was performed between radiologic densities in Hounsfield units and biomechanical stiffness. Collagen I samples had superior bone formation at 6 weeks as demonstrated by volume computed tomographic scanning, with densities of 300 HU, similar to native bone, and the highest compression values. Bone specificity of new tissue was confirmed histologically and by the expression of alkaline phosphatase, osteonectin, osteopontin, and osteocalcin. The bone density correlated closely with histologic and biomechanical testing results. Bone formation is supported best by β-tricalcium phosphate/collagen I hydrogel and mesenchymal stem cells in collagen I hydrogel. Therapeutic, V.

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

    PubMed

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

    2017-06-01

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

  3. A novel route in bone tissue engineering: magnetic biomimetic scaffolds.

    PubMed

    Bock, N; Riminucci, A; Dionigi, C; Russo, A; Tampieri, A; Landi, E; Goranov, V A; Marcacci, M; Dediu, V

    2010-03-01

    In recent years, interest in tissue engineering and its solutions has increased considerably. In particular, scaffolds have become fundamental tools in bone graft substitution and are used in combination with a variety of bio-agents. However, a long-standing problem in the use of these conventional scaffolds lies in the impossibility of re-loading the scaffold with the bio-agents after implantation. This work introduces the magnetic scaffold as a conceptually new solution. The magnetic scaffold is able, via magnetic driving, to attract and take up in vivo growth factors, stem cells or other bio-agents bound to magnetic particles. The authors succeeded in developing a simple and inexpensive technique able to transform standard commercial scaffolds made of hydroxyapatite and collagen in magnetic scaffolds. This innovative process involves dip-coating of the scaffolds in aqueous ferrofluids containing iron oxide nanoparticles coated with various biopolymers. After dip-coating, the nanoparticles are integrated into the structure of the scaffolds, providing the latter with magnetization values as high as 15 emu g(-)(1) at 10 kOe. These values are suitable for generating magnetic gradients, enabling magnetic guiding in the vicinity and inside the scaffold. The magnetic scaffolds do not suffer from any structural damage during the process, maintaining their specific porosity and shape. Moreover, they do not release magnetic particles under a constant flow of simulated body fluids over a period of 8 days. Finally, preliminary studies indicate the ability of the magnetic scaffolds to support adhesion and proliferation of human bone marrow stem cells in vitro. Hence, this new type of scaffold is a valuable candidate for tissue engineering applications, featuring a novel magnetic guiding option. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2010-01-01

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

  5. Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound

    NASA Astrophysics Data System (ADS)

    Moros, Eduardo G.; Novak, Petr; Straube, William L.; Kolluri, Prashant; Yablonskiy, Dmitriy A.; Myerson, Robert J.

    2004-03-01

    The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue-bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue-bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater

  6. Orientation and size-dependent mechanical modulation within individual secondary osteons in cortical bone tissue

    PubMed Central

    Carnelli, Davide; Vena, Pasquale; Dao, Ming; Ortiz, Christine; Contro, Roberto

    2013-01-01

    Anisotropy is one of the most peculiar aspects of cortical bone mechanics; however, its anisotropic mechanical behaviour should be treated only with strict relationship to the length scale of investigation. In this study, we focus on quantifying the orientation and size dependence of the spatial mechanical modulation in individual secondary osteons of bovine cortical bone using nanoindentation. Tests were performed on the same osteonal structure in the axial (along the long bone axis) and transverse (normal to the long bone axis) directions along arrays going radially out from the Haversian canal at four different maximum depths on three secondary osteons. Results clearly show a periodic pattern of stiffness with spatial distance across the osteon. The effect of length scale on lamellar bone anisotropy and the critical length at which homogenization of the mechanical properties occurs were determined. Further, a laminate-composite-based analytical model was applied to the stiffness trends obtained at the highest spatial resolution to evaluate the elastic constants for a sub-layer of mineralized collagen fibrils within an osteonal lamella on the basis of the spatial arrangement of the fibrils. The hierarchical arrangement of lamellar bone is found to be a major determinant for modulation of mechanical properties and anisotropic mechanical behaviour of the tissue. PMID:23389895

  7. Methods: a comparative analysis of radiography, microcomputed tomography, and histology for bone tissue engineering.

    PubMed

    Hedberg, Elizabeth L; Kroese-Deutman, Henriette C; Shih, Charles K; Lemoine, Jeremy J; Liebschner, Michael A K; Miller, Michael J; Yasko, Alan W; Crowther, Roger S; Carney, Darrell H; Mikos, Antonios G; Jansen, John A

    2005-01-01

    This study focused on the assessment of radiography, microcomputed tomography, and histology for the evaluation of bone formation in a 15.0-mm defect in the rabbit radius after the implantation of a tissue-engineered construct. Radiography was found to be useful as a noninvasive method for obtaining images of calcified tissue throughout the time course of the experiment. With this method, however, image quality was low, making it difficult to obtain precise information about the location and quantity of the bone formed. Microcomputed tomography was used to create three-dimensional reconstructions of the bone (25-microm resolution). These reconstructions allowed for greater spatial resolution than the radiography, but did not allow for imaging of the implanted scaffold material or the surrounding, nonmineralized tissue. To visualize all materials within the defect area at the cellular level, histology was used. Histological analysis, however, is a destructive technique that did not allow for any further analysis of the samples. Each technique examined here has its own advantages and limitations, but each yields unique information regarding bone regeneration. It is only through the use of all three techniques that complete characterization of the bone growth and tissue/construct responses after implantation in vivo.

  8. Peptide-laden mesoporous silica nanoparticles with promoted bioactivity and osteo-differentiation ability for bone tissue engineering.

    PubMed

    Luo, Zuyuan; Deng, Yi; Zhang, Ranran; Wang, Mengke; Bai, Yanjie; Zhao, Qiang; Lyu, Yalin; Wei, Jie; Wei, Shicheng

    2015-07-01

    Combination of mesoporous silica materials and bioactive factors is a promising niche-mimetic solution as a hybrid bone substitution for bone tissue engineering. In this work, we have synthesized biocompatible silica-based nanoparticles with abundant mesoporous structure, and incorporated bone-forming peptide (BFP) derived from bone morphogenetic protein-7 (BMP-7) into the mesoporous silica nanoparticles (MSNs) to obtain a slow-release system for osteogenic factor delivery. The chemical characterization demonstrates that the small osteogenic peptide is encapsulated in the mesoporous successfully, and the nitrogen adsorption-desorption isotherms suggest that the peptide encapsulation has no influence on mesoporous structure of MSNs. In the cell experiment, the peptide-laden MSNs (p-MSNs) show higher MG-63 cell proliferation, spreading and alkaline phosphatase (ALP) activity than the bare MSNs, indicating good in vitro cytocompatibility. Simultaneously, the osteogenesis-related proteins expression and calcium mineral deposition disclose enhanced osteo-differentiation of human mesenchymal stem cells (hMSCs) under the stimulation of the p-MSNs, confirming that BFP released from MSNs could significantly promote the osteogenic differentiation of hMSCs, especially at 500μg/mL of p-MSNs concentration. The peptide-modified MSNs with better bioactivity and osteogenic differentiation make it a potential candidate as bioactive material for bone repairing, bone regeneration, and bio-implant coating applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Composite Bone and Soft Tissue Loss Treated with Distraction Histiogenesis

    DTIC Science & Technology

    2010-01-01

    their frames removed had healed docking sites, and the fourth whose frame remained in place had a healing fracture without evidence of delayed union ...interventions (3–8). The goals of limb salvage surgery in this setting are to restore length and alignment, regenerate bone loss, obtain fracture union ...angulation to manage composite bone and soft tissue loss associated with combat-related type IIIB open tibia fractures . Four patients underwent placement

  10. 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

  11. Coculture strategies in bone tissue engineering: the impact of culture conditions on pluripotent stem cell populations.

    PubMed

    Janardhanan, Sathyanarayana; Wang, Martha O; Fisher, John P

    2012-08-01

    The use of pluripotent stem cell populations for bone tissue regeneration provides many opportunities and challenges within the bone tissue engineering field. For example, coculture strategies have been utilized to mimic embryological development of bone tissue, and particularly the critical intercellular signaling pathways. While research in bone biology over the last 20 years has expanded our understanding of these intercellular signaling pathways, we still do not fully understand the impact of the system's physical characteristics (orientation, geometry, and morphology). This review of coculture literature delineates the various forms of coculture systems and their respective outcomes when applied to bone tissue engineering. To understand fully the key differences between the different coculture methods, we must appreciate the underlying paradigms of physiological interactions. Recent advances have enabled us to extrapolate these techniques to larger dimensions and higher geometric resolutions. Finally, the contributions of bioreactors, micropatterned biomaterials, and biomaterial interaction platforms are evaluated to give a sense of the sophistication established by a combination of these concepts with coculture systems.

  12. 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.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2007-02-01

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

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

    PubMed

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

    2012-06-01

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

  16. Reduced graphene oxide aerogel networks with soft interfacial template for applications in bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Asha, S.; Ananth, A. Nimrodh; Jose, Sujin P.; Rajan, M. A. Jothi

    2018-05-01

    Reduced Graphene Oxide aerogels (A-RGO), functionalized with chitosan, were found to induce and/or accelerate the mineralization of hydroxyapatite. The functionalized chitosan acts as a soft interfacial template on the surface of A-RGO assisting the growth of hydroxyapatite particles. The mineralization on these soft aerogel networks was performed by soaking the aerogels in simulated body fluid, relative to time. Polymer-induced mineralization exhibited an ordered arrangement of hydroxyapatite particles on reduced graphene oxide aerogel networks with a higher crystalline index (IC) of 1.7, which mimics the natural bone formation indicating the importance of the polymeric interfacial template. These mineralized aerogels which mimic the structure and composition of natural bone exhibit relatively higher rate of cell proliferation, osteogenic differentiation and osteoid matrix formation proving it to be a potential scaffold for bone tissue regeneration.

  17. Learning from evolutionary optimisation: what are toughening mechanisms good for in dentine, a nonrepairing bone tissue?

    PubMed

    Zaslansky, Paul; Currey, John D; Fleck, Claudia

    2016-09-12

    The main mass of material found in teeth is dentine, a bone-like tissue, riddled with micron-sized tubules and devoid of living cells. It provides support to the outer wear-resistant layer of enamel, and exhibits toughening mechanisms which contribute to crack resistance. And yet unlike most bone tissues, dentine does not remodel and consequently any accumulated damage does not 'self repair'. Because damage containment followed by tissue replacement is a prime reason for the crack-arresting microstructures found in most bones, the occurrence of toughening mechanisms without the biological capability to repair is puzzling. Here we consider the notion that dentine might be overdesigned for strength, because it has to compensate for the lack of cell-mediated healing mechanisms. Based on our own and on literature-reported observations, including quasistatic and fatigue properties, dentine design principles are discussed in light of the functional conditions under which teeth evolved. We conclude that dentine is only slightly overdesigned for everyday cyclic loading because usual mastication stresses may come close to its endurance strength. The in-built toughening mechanisms constitute an evolutionary benefit because they prevent catastrophic failure during rare overload events, which was probably very advantageous in our hunter gatherer ancestor times. From a bio-inspired perspective, understanding the extent of evolutionary overdesign might be useful for optimising biomimetic structures used for load bearing.

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

    PubMed

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

    2015-03-01

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

  19. Involvement of CD147 in alveolar bone remodeling and soft tissue degradation in experimental periodontitis.

    PubMed

    Yang, D; Liu, R; Liu, L; Liao, H; Wang, C; Cao, Z

    2017-08-01

    The objective of this study was to investigate the possible roles of clusters of differentiation 147 (CD147) in bone resorption and mineralization through the bone markers of bone sialoprotein, osteocalcin, osteopontin and alkaline phosphatase (ALP), trabecular structure of alveolar bone and number of osteoclasts. We also investigated the effects of CD147 on inflammation and collagen breakdown. Twenty-eight male Wistar rats were randomly divided into four groups of seven animals each: healthy group, periodontitis group, periodontitis + saline group and periodontitis + anti-CD147 groups. Hematoxylin and eosin staining were used for histological assessment. Alveolar bone loss and trabecula microstructure were evaluated using micro-computed tomography. Collagen fiber breakdown was assessed via picrosirius red staining. Tartrate-resistant acid phosphatase staining was conducted for osteoclast analysis. The expressions of ALP, bone sialoprotein, osteocalcin and osteopontin were evaluated using immunohistochemistry. Anti-CD147 treatment significantly inhibited alveolar bone loss and osteoclastogenesis, and improved the bone volume/tissue volume, and the trabecular thickness of alveolar bone. Histological staining revealed that anti-CD147 significantly reduced the infiltration of inflammation and limited the fractions of degraded areas in collagen fibers. The expression of bone markers (ALP, bone sialoprotein, osteocalcin and osteopontin) was enhanced by anti-CD147 treatment. The results of the anti-CD147 treatment indicate that CD147 was involved in alveolar bone mineralization, osteoclastogenesis and trabecular microstructure. The inhibition of CD147 could increase the expression level of osteogenic markers, alveolar bone crest height and suppressed collagen fiber degradation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Mutual cancellation between tones presented by air conduction, by bone conduction and by non-osseous (soft tissue) bone conduction.

    PubMed

    Chordekar, Shai; Kriksunov, Leonid; Kishon-Rabin, Liat; Adelman, Cahtia; Sohmer, Haim

    2012-01-01

    Auditory sensation can be elicited not only by air conducted (AC) sound or bone conducted (BC) sound, but also by stimulation of soft tissue (STC) sites on the head and neck relatively distant from deeply underlying bone. Tone stimulation by paired combinations of AC with BC (mastoid) and/or with soft tissue conduction produce the same pitch sensation, mutual masking and beats. The present study was designed to determine whether they can also cancel each other. The study was conducted on ten normal hearing subjects. Tones at 2 kHz were presented in paired combinations by AC (insert earphone), by BC (bone vibrator) at the mastoid, and by the same bone vibrator to several STC sites; e.g. the neck, the sterno-cleido-mastoid muscle, the eye, and under the chin, shifting the phases between the pairs. Subjects reported changes in loudness and cancellation. The phase for cancellation differed across subjects. Neck muscle manipulations (changes in head position) led to alterations in the phase at which cancellation was reported. Cancellation was also achieved between pairs of tones to two STC sites. The differing phases for cancellation across subjects and the change in phase accompanying different head positions may be due to the different acoustic impedances of the several tissues in the head and neck. A major component of auditory stimulation by STC may not induce actual skull bone vibrations and may not involve bulk fluid volume displacements. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. 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

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

    PubMed

    Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

    2018-02-01

     Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties.

    PubMed

    Mabilleau, Guillaume; Mieczkowska, Aleksandra; Irwin, Nigel; Simon, Yannick; Audran, Maurice; Flatt, Peter R; Chappard, Daniel

    2014-06-01

    Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4 weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Bone tissue heterogeneity is associated with fracture toughness: a polarization Raman spectroscopy study

    NASA Astrophysics Data System (ADS)

    Makowski, Alexander J.; Granke, Mathilde; Uppuganti, Sasidhar; Mahadevan-Jansen, Anita; Nyman, Jeffry S.

    2015-02-01

    Polarization Raman Spectroscopy has been used to demonstrate microstructural features and collagen fiber orientation in human and mouse bone, concurrently measuring both organization and composition; however, it is unclear as to what extent these measurements explain the mechanical quality of bone. In a cohort of age and gender matched cadaveric cortical bone samples (23-101 yr.), we show homogeneity of both composition and structure are associated with the age related decrease in fracture toughness. 64 samples were machined into uniform specimens and notched for mechanical fracture toughness testing and polished for Raman Spectroscopy. Fingerprint region spectra were acquired on wet bone prior to mechanical testing by sampling nine different microstructural features spaced in a 750x750 μm grid in the region of intended crack propagation. After ASTM E1820 single edge notched beam fracture toughness tests, the sample was dried in ethanol and the osteonal-interstitial border of one osteon was samples in a 32x32 grid of 2μm2 pixels for two orthogonal orientations relative to the long bone axis. Standard peak ratios from the 9 separate microstructures show heterogeneity between structures but do not sufficiently explain fracture toughness; however, peak ratios from mapping highlight both lamellar contrast (ν1Phos/Amide I) and osteon-interstitial contrast (ν1Phos/Proline). Combining registered orthogonal maps allowed for multivariate analysis of underlying biochemical signatures. Image entropy and homogeneity metrics of single principal components significantly explain resistance to crack initiation and propagation. Ultimately, a combination of polarization content and multivariate Raman signatures allowed for the association of microstructural tissue heterogeneity with fracture resistance.

  7. Segmentation of bone structures in 3D CT images based on continuous max-flow optimization

    NASA Astrophysics Data System (ADS)

    Pérez-Carrasco, J. A.; Acha-Piñero, B.; Serrano, C.

    2015-03-01

    In this paper an algorithm to carry out the automatic segmentation of bone structures in 3D CT images has been implemented. Automatic segmentation of bone structures is of special interest for radiologists and surgeons to analyze bone diseases or to plan some surgical interventions. This task is very complicated as bones usually present intensities overlapping with those of surrounding tissues. This overlapping is mainly due to the composition of bones and to the presence of some diseases such as Osteoarthritis, Osteoporosis, etc. Moreover, segmentation of bone structures is a very time-consuming task due to the 3D essence of the bones. Usually, this segmentation is implemented manually or with algorithms using simple techniques such as thresholding and thus providing bad results. In this paper gray information and 3D statistical information have been combined to be used as input to a continuous max-flow algorithm. Twenty CT images have been tested and different coefficients have been computed to assess the performance of our implementation. Dice and Sensitivity values above 0.91 and 0.97 respectively were obtained. A comparison with Level Sets and thresholding techniques has been carried out and our results outperformed them in terms of accuracy.

  8. Microporous nanofibrous fibrin-based scaffolds for craniofacial bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Osathanon, Thanaphum

    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 and immobilized alkaline phosphatase fibrin scaffolds with tightly controllable pore size, pore interconnection has been investigated. Microporous, nanofibrous fibrin scaffolds (FS) were fabricated using sphere-templating method. Calcium phosphate/fibrin 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 (MFS) exhibited significantly higher alkaline phosphatase activity as well as osteoblast marker gene expression compared to FS and nHA incorporated fibrin scaffolds (nHA/FS). These fibrin-based 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. The second approach was to immobilize alkaline phosphatase (ALP) on fibrin scaffolds. ALP enzyme was covalently immobilized on the microporous nanofibrous fibrin scaffolds using 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (EDC). The SEM results demonstrated mineral deposition on immobilized ALP fibrin scaffolds (ALP/FS) when incubated in medium supplemented with beta-glycerophosphate, suggesting that the

  9. Indentation size effect of cortical bones submitted to different soft tissue removals.

    PubMed

    Bandini, A; Chicot, D; Berry, P; Decoopman, X; Pertuz, A; Ojeda, D

    2013-04-01

    Properties of elasticity, hardness and viscosity are determined for the study of the visco-elastoplastic behavior of bones. The mechanical properties are compared in two upright sections of the bone due to their anisotropy. Besides, influence of hydration treatments leading to structural modifications of collagen and ground substance contents of bones on the mechanical properties is studied on a femoral cortical bovine bone. The treatments applied to the bone are used by forensic anthropologists to remove the soft tissue and modifying the hydration degree coupled to the collagen content. From instrumented indentation experiments, the hardness is characterized by the macrohardness and a hardness length-scale factor stating the hardness-load dependence. The elastic modulus results from the application of the methodology of Oliver and Pharr (1992). The coefficient of viscosity is deduced from a rheological model representing the indenter time-displacement observed under the application of a constant load. As a result, all the mechanical properties are found to be lower in the transverse section in an extent depending on the hydration treatment, i.e. the different values are located between 5% and 25% for the hardness around 0.5GPa, between 25% and 40% for the elastic modulus around 20GPa and between 2% and 35% for the coefficient of viscosity around 60GPa.s. Unexpectedly, the elastic modulus to coefficient of viscosity ratio is found to be independent on the hydration treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2014-11-01

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

  12. Anorexia Nervosa, Obesity and Bone Metabolism

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa and obesity are conditions at the extreme ends of the nutritional spectrum, associated with marked reductions versus increases respectively in body fat content. Both conditions are also associated with an increased risk for fractures. In anorexia nervosa, body composition and hormones secreted or regulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, anorexia nervosa is characterized by increases in marrow adiposity and decreases in cold activated brown adipose tissue, both of which are related to low bone density. In obese individuals, greater visceral adiposity is associated with greater marrow fat, lower bone density and impaired bone structure. In this review, we discuss bone metabolism in anorexia nervosa and obesity in relation to adipose tissue distribution and hormones secreted or regulated by body fat content. PMID:24079076

  13. Heparin functionalization increases retention of TGF-β2 and GDF5 on biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering.

    PubMed

    Font Tellado, Sònia; Chiera, Silvia; Bonani, Walter; Poh, Patrina S P; Migliaresi, Claudio; Motta, Antonella; Balmayor, Elizabeth R; van Griensven, Martijn

    2018-05-01

    The tendon/ligament-to-bone transition (enthesis) is a highly specialized interphase tissue with structural gradients of extracellular matrix composition, collagen molecule alignment and mineralization. These structural features are essential for enthesis function, but are often not regenerated after injury. Tissue engineering is a promising strategy for enthesis repair. Engineering of complex tissue interphases such as the enthesis is likely to require a combination of biophysical, biological and chemical cues to achieve functional tissue regeneration. In this study, we cultured human primary adipose-derived mesenchymal stem cells (AdMCs) on biphasic silk fibroin scaffolds with integrated anisotropic (tendon/ligament-like) and isotropic (bone/cartilage like) pore alignment. We functionalized those scaffolds with heparin and explored their ability to deliver transforming growth factor β2 (TGF-β2) and growth/differentiation factor 5 (GDF5). Heparin functionalization increased the amount of TGF-β2 and GDF5 remaining attached to the scaffold matrix and resulted in biological effects at low growth factor doses. We analyzed the combined impact of pore alignment and growth factors on AdMSCs. TGF-β2 and pore anisotropy synergistically increased the expression of tendon/ligament markers and collagen I protein content. In addition, the combined delivery of TGF-β2 and GDF5 enhanced the expression of cartilage markers and collagen II protein content on substrates with isotropic porosity, whereas enthesis markers were enhanced in areas of mixed anisotropic/isotropic porosity. Altogether, the data obtained in this study improves current understanding on the combined effects of biological and structural cues on stem cell fate and presents a promising strategy for tendon/ligament-to-bone regeneration. Regeneration of the tendon/ligament-to-bone interphase (enthesis) is of significance in the repair of ruptured tendons/ligaments to bone to improve implant integration and

  14. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, James W.

    1995-01-01

    A device for stimulating bone tissue by applying a low level alternating current signal directly to the patient's skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures.

  15. Raloxifene microsphere-embedded collagen/chitosan/β-tricalcium phosphate scaffold for effective bone tissue engineering.

    PubMed

    Zhang, Ming-Lei; Cheng, Ji; Xiao, Ye-Chen; Yin, Ruo-Feng; Feng, Xu

    2017-02-25

    Engineering novel scaffolds that can mimic the functional extracellular matrix (ECM) would be a great achievement in bone tissue engineering. This paper reports the fabrication of novel collagen/chitosan/β-tricalcium phosphate (CCTP) based tissue engineering scaffold. In order to improve the regeneration ability of scaffold, we have embedded raloxifene (RLX)-loaded PLGA microsphere in the CCTP scaffold. The average pore of scaffold was in the range of 150-200μm with ideal mechanical strength and swelling/degradation characteristics. The release rate of RLX from the microsphere (MS) embedded scaffold was gradual and controlled. Also a significantly enhanced cell proliferation was observed in RLX-MS exposed cell group suggesting that microsphere/scaffold could be an ideal biomaterial for bone tissue engineering. Specifically, RLX-MS showed a significantly higher Alizarin red staining indicating the higher mineralization capacity of this group. Furthermore, a high alkaline phosphatase (ALP) activity for RLX-MS exposed group after 15days incubation indicates the bone regeneration capacity of MC3T3-E1 cells. Overall, present study showed that RLX-loaded microsphere embedded scaffold has the promising potential for bone tissue engineering applications. Copyright © 2016. Published by Elsevier B.V.

  16. Network-Based Method for Identifying Co-Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues

    PubMed Central

    Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Cai, Yu-Dong

    2017-01-01

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein–protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method. PMID:28974058

  17. Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

    PubMed

    Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

    2017-10-02

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

  18. 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.

  19. Vascularization of repaired limb bone defects using chitosan-β-tricalcium phosphate composite as a tissue engineering bone scaffold.

    PubMed

    Yang, Le; Wang, Qinghua; Peng, Lihua; Yue, Hong; Zhang, Zhendong

    2015-08-01

    Ensuring histocompatibility in the tissue engineering of bones is a complex issue. The aim of this study was to observe the feasibility of chitosan-β-tricalcium phosphate composite in repairing limb bone defects, and to evaluate the therapeutic effects on osteogenesis. Beagle mesenchymal stem cells (MSCs) were divided into an experimental group that was cultured with an injectable form of chitosan-β-tricalcium phosphate composite and a control group. The effect of the composite on bone tissue growth was evaluated by MTT assay. In addition, 12-month-old beagles were subjected to 15-mm femur defects and subsequently implanted with scaffolds to observe the effects on osteogenesis and vascularization. The dogs were subdivided into two groups of five animals: Group A, which was implanted with scaffold-MSC compounds, and Group B, which was implanted with scaffolds alone. The dogs were observed on the 2nd, 4th, 8th and 12th weeks post-implantation. Scanning electron microscopy analysis revealed that the composite was compatible with MSCs, with similar outcomes in the control and experimental groups. MTT analysis additionally showed that the MSCs in the experimental group grew in a similar manner to those in the control group. The composite did not significantly affect the MSC growth or proliferation. In combination with MSCs, the scaffold materials were effective in the promotion of osteogenesis and vascularization. In conclusion, the chitosan-β-tricalcium phosphate composite was compatible with the MSCs and did not affect cellular growth or proliferation, therefore proving to be an effective injectable composite for tissue engineered bone. Simultaneous implantation of stem cells with a carrier composite proved to function effectively in the repair of bone defects.

  20. Pore size regulates cell and tissue interactions with PLGA-CaP scaffolds used for bone engineering.

    PubMed

    Sicchieri, Luciana Gonçalves; Crippa, Grasiele Edilaine; de Oliveira, Paulo Tambasco; Beloti, Marcio Mateus; Rosa, Adalberto Luiz

    2012-02-01

    A common subject in bone tissue engineering is the need for porous scaffolds to support cell and tissue interactions aiming at repairing bone tissue. As poly(lactide-co-glycolide)-calcium phosphate (PLGA-CaP) scaffolds can be manufactured with different pore sizes, the aim of this study was to evaluate the effect of pore diameter on osteoblastic cell responses and bone tissue formation. Scaffolds were prepared with 85% porosity, with pore diameters in the ranges 470-590, 590-850 and 850-1200 µm. Rat bone marrow stem cells differentiated into osteoblasts were cultured on the scaffolds for up to 10 days to evaluate cell growth, alkaline phosphatase (ALP) activity and the gene expression of the osteoblast markers RUNX2, OSX, COL, MSX2, ALP, OC and BSP by real-time PCR. Scaffolds were implanted in critical size rat calvarial defects for 2, 4, and 8 weeks for histomorphometric analysis. Cell growth and ALP activity were not affected by the pore size; however, there was an increase in the gene expression of osteoblastic markers with the increase in the pore sizes. At 2 weeks all scaffolds displayed a similar amount of bone and blood vessels formation. At 4 and 8 weeks much more bone formation and an increased number of blood vessels were observed in scaffolds with pores of 470-590 µm. These results show that PLGA-CaP is a promising biomaterial for bone engineering. However, ideally, combinations of larger (-1000 µm) and smaller (-500 µm) pores in a single scaffold would optimize cellular and tissue responses during bone healing. Copyright © 2011 John Wiley & Sons, Ltd.

  1. [Bone structure in rheumatoid arthritis].

    PubMed

    Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

    2013-07-01

    In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

  2. Electrospun nanofibres to mimic natural hierarchical structure of tissues: application in musculoskeletal regeneration.

    PubMed

    Sankar, Sharanya; Sharma, Chandra S; Rath, Subha N; Ramakrishna, Seeram

    2018-01-01

    Biomimetic scaffolds mimicking the natural hierarchical structure of tissues have recently attracted the interest of researchers and provide a promising strategy to resemble the nonhomogeneous property of tissues. This review provides an overview of the various hierarchical length scales in the native tissues of the musculoskeletal system. It further focuses on electrospinning as a technique to mimic the tissue structures with specific emphasis on bone. The effect of cellular alignment, infiltration, vascularisation, and differentiation in these nanostructures has also been discussed. An outline of the various additive manufacturing techniques in combination with electrospinning has been elaborated. The review concludes with the challenges and future directions to understand the intricacies of bottom-up approach to engineer the systems at a macroscale. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Controlled delivery of icariin on small intestine submucosa for bone tissue engineering.

    PubMed

    Li, Mei; Gu, Qiaoqiao; Chen, Mengjie; Zhang, Chi; Chen, Songdi; Zhao, Jiyuan

    2017-02-01

    Small intestine submucosa (SIS) has been reported as an excellent biomaterial for tissue engineering because of its naturally occurring collagenous extracellular matrix property with growth factors. However, SIS from submucosal layer of intestine provides different microenvironment from bone tissue, which limits its application to bone regeneration. The object of this study was to improve osteoinductivity of SIS by controlled local delivery of icariin (Ic), a potent osteogenic compound. Sustained release of icariin from SIS scaffold was achieved for >30days and the loading of icariin on SIS scaffold was uniform as scanned by SEM. In vitro experiments revealed that expression of osteogenic differentiation markers (Alp, Bsp and Ocn) was increased after treatment of Ic-SIS scaffold, without significant cytotoxicity. In an in vivo mouse calvarial defect model, bone regeneration was enhanced by SIS implantation at 8weeks, compared to control defect. New bone formation was further improved by implantation with Ic-SIS (low and high) at both 4 and 8weeks. The results of this study suggest that SIS scaffold has the potential as an icariin delivery carrier for enhancement of bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Fabrication of 3D porous silk scaffolds by particulate (salt/sucrose) leaching for bone tissue reconstruction.

    PubMed

    Park, Hyun Jung; Lee, Ok Joo; Lee, Min Chae; Moon, Bo Mi; Ju, Hyung Woo; Lee, Jung min; Kim, Jung-Ho; Kim, Dong Wook; Park, Chan Hum

    2015-01-01

    Silk fibroin is a biomaterial being actively studied in the field of bone tissue engineering. In this study, we aimed to select the best strategy for bone reconstruction on scaffolds by changing various conditions. We compared the characteristics of each scaffold via structural analysis using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), the swelling ratio, water uptake, porosity, compressive strength, cell infiltration and cell viability (CCK-8). The scaffolds had high porosity with good inter pore connectivity and showed high compressive strength and modulus. In addition, to confirm bone reconstruction, animal studies were conducted in which samples were implanted in rat calvaria and investigated by micro-CT scans. In conclusion, the presented study indicates that using sucrose produces scaffolds showing better pore interconnectivity and cell infiltration than scaffolds made by using a salt process. In addition, in vivo experiments showed that hydroxyapatite accelerates bone reconstruction on implanted scaffolds. Accordingly, our scaffold will be expected to have a useful application in bone reconstruction. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. [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.

  6. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue.

    PubMed

    Shi, Yan-Chuan; Baldock, Paul A

    2012-02-01

    Skeletal research is currently undergoing a period of marked expansion. The boundaries of "bone" research are being re-evaluated and with this, a growing recognition of a more complex and interconnected biology than previously considered. One aspect that has become the focus of particular attention is the relationship between bone and fat homeostasis. Evidence from a number of avenues indicates that bone and adipose regulation are both related and interdependent. This review examines the neuropeptide Y (NPY) system, known to exert powerful control over both bone and fat tissue. The actions of this system are characterized by signaling both within specific nuclei of the hypothalamus and also the target tissues, mediated predominantly through two G-protein coupled receptors (Y1 and Y2). In bone tissue, elevated NPY levels act consistently to repress osteoblast activity. Moreover, both central Y2 receptor and osteoblastic Y1 receptor signaling act similarly to repress bone formation. Conversely, loss of NPY expression or receptor signaling induces increased osteoblast activity and bone mass in both cortical and cancellous envelopes. In fat tissue, NPY action is more complex. Energy homeostasis is powerfully altered by elevations in hypothalamic NPY, resulting in increases in fat accretion and body-wide energy conservation, through the action of locally expressed Y1 receptors, while local Y2 receptors act to inhibit NPY-ergic tone. Loss of central NPY expression has a markedly reduced effect, consistent with a physiological drive to promote fat accretion. In fat tissue, NPY and Y1 receptors act to promote lipogenesis, consistent with their roles in the brain. Y2 receptors expressed in adipocytes also act in this manner, showing an opposing action to their role in the hypothalamus. While direct investigation of these processes has yet to be completed, these responses appear to be interrelated to some degree. The starvation-based signal of elevated central NPY inducing

  7. Mechanical Properties of Optimized Diamond Lattice Structure for Bone Scaffolds Fabricated via Selective Laser Melting.

    PubMed

    Liu, Fei; Zhang, David Z; Zhang, Peng; Zhao, Miao; Jafar, Salman

    2018-03-03

    Developments in selective laser melting (SLM) have enabled the fabrication of periodic cellular lattice structures characterized by suitable properties matching the bone tissue well and by fluid permeability from interconnected structures. These multifunctional performances are significantly affected by cell topology and constitutive properties of applied materials. In this respect, a diamond unit cell was designed in particular volume fractions corresponding to the host bone tissue and optimized with a smooth surface at nodes leading to fewer stress concentrations. There were 33 porous titanium samples with different volume fractions, from 1.28 to 18.6%, manufactured using SLM. All of them were performed under compressive load to determine the deformation and failure mechanisms, accompanied by an in-situ approach using digital image correlation (DIC) to reveal stress-strain evolution. The results showed that lattice structures manufactured by SLM exhibited comparable properties to those of trabecular bone, avoiding the effects of stress-shielding and increasing longevity of implants. The curvature of optimized surface can play a role in regulating the relationship between density and mechanical properties. Owing to the release of stress concentration from optimized surface, the failure mechanism of porous titanium has been changed from the pattern of bottom-up collapse by layer (or cell row) to that of the diagonal (45°) shear band, resulting in the significant enhancement of the structural strength.

  8. Mechanical Properties of Optimized Diamond Lattice Structure for Bone Scaffolds Fabricated via Selective Laser Melting

    PubMed Central

    Zhang, David Z.; Zhang, Peng; Zhao, Miao; Jafar, Salman

    2018-01-01

    Developments in selective laser melting (SLM) have enabled the fabrication of periodic cellular lattice structures characterized by suitable properties matching the bone tissue well and by fluid permeability from interconnected structures. These multifunctional performances are significantly affected by cell topology and constitutive properties of applied materials. In this respect, a diamond unit cell was designed in particular volume fractions corresponding to the host bone tissue and optimized with a smooth surface at nodes leading to fewer stress concentrations. There were 33 porous titanium samples with different volume fractions, from 1.28 to 18.6%, manufactured using SLM. All of them were performed under compressive load to determine the deformation and failure mechanisms, accompanied by an in-situ approach using digital image correlation (DIC) to reveal stress–strain evolution. The results showed that lattice structures manufactured by SLM exhibited comparable properties to those of trabecular bone, avoiding the effects of stress-shielding and increasing longevity of implants. The curvature of optimized surface can play a role in regulating the relationship between density and mechanical properties. Owing to the release of stress concentration from optimized surface, the failure mechanism of porous titanium has been changed from the pattern of bottom-up collapse by layer (or cell row) to that of the diagonal (45°) shear band, resulting in the significant enhancement of the structural strength. PMID:29510492

  9. Dual-source dual-power electrospinning and characteristics of multifunctional scaffolds for bone tissue engineering.

    PubMed

    Wang, Chong; Wang, Min

    2012-10-01

    Electrospun tissue engineering scaffolds are attractive due to their distinctive advantages over other types of scaffolds. As both osteoinductivity and osteoconductivity play crucial roles in bone tissue engineering, scaffolds possessing both properties are desirable. In this investigation, novel bicomponent scaffolds were constructed via dual-source dual-power electrospinning (DSDPES). One scaffold component was emulsion electrospun poly(D,L-lactic acid) (PDLLA) nanofibers containing recombinant human bone morphogenetic protein (rhBMP-2), and the other scaffold component was electrospun calcium phosphate (Ca-P) particle/poly(lactic-co-glycolic acid) (PLGA) nanocomposite fibers. The mass ratio of rhBMP-2/PDLLA fibers to Ca-P/PLGA fibers in bicomponent scaffolds could be controlled in the DSDPES process by adjusting the number of syringes used to supply solutions for electrospinning. Through process optimization, both types of fibers could be evenly distributed in bicomponent scaffolds. The structure and properties of each type of fibers in the scaffolds were studied. The morphological and structural properties and wettability of scaffolds were assessed. The effects of emulsion composition for rhBMP-2/PDLLA fibers and mass ratio of fibrous components in bicomponent scaffolds on in vitro release of rhBMP-2 from scaffolds were investigated. In vitro degradation of scaffolds was also studied by monitoring their morphological changes, weight losses and decreases in average molecular weight of fiber matrix polymers.

  10. Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

    PubMed

    Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

    2018-02-01

    Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

  11. Preparation and characterization of a three-dimensional printed scaffold based on a functionalized polyester for bone tissue engineering applications.

    PubMed

    Seyednejad, Hajar; Gawlitta, Debby; Dhert, Wouter J A; van Nostrum, Cornelus F; Vermonden, Tina; Hennink, Wim E

    2011-05-01

    At present there is a strong need for suitable scaffolds that meet the requirements for bone tissue engineering applications. The objective of this study was to investigate the suitability of porous scaffolds based on a hydroxyl functionalized polymer, poly(hydroxymethylglycolide-co-ε-caprolactone) (pHMGCL), for tissue engineering. In a recent study this polymer was shown to be a promising material for bone regeneration. The scaffolds consisting of pHMGCL or poly(ε-caprolactone) (PCL) were produced by means of a rapid prototyping technique (three-dimensional plotting) and were shown to have a high porosity and an interconnected pore structure. The thermal and mechanical properties of both scaffolds were investigated and human mesenchymal stem cells were seeded onto the scaffolds to evaluate the cell attachment properties, as well as cell viability and differentiation. It was shown that the cells filled the pores of the pHMGCL scaffold within 7 days and displayed increased metabolic activity when compared with cells cultured in PCL scaffolds. Importantly, pHMGCL scaffolds supported osteogenic differentiation. Therefore, scaffolds based on pHMGCL are promising templates for bone tissue engineering applications. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2014-11-09

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

  13. The influence of the cumulated deformation energy in the measurement by the DSI method on the selected mechanical properties of bone tissues.

    PubMed

    Makuch, Anna M; Skalski, Konstanty R; Pawlikowski, Marek

    2017-01-01

    The goal of the study was to determine the influence of DSI test conditions, i.e., loading/unloading rates, hold time, and the value of the maximum loading force on selected mechanical properties of trabecular bone tissue. The test samples were resected from a femoral head of a patient qualified for a hip replacement surgery. During the DSI tests hardness (HV, HM, HIT) and elastic modulus (EIT) of trabecular bone tissue were measured using the Micro Hardness Tester (MHT, CSEM). The analysis of the results of measurements and the calculations of total energy, i.e., elastic and inelastic (Wtotal, Welastic, Winelastic) and those of hardness and elasticity made it possible to assess the impact of the process parameters (loading velocity, force and hold time) on mechanical properties of bone structures at a microscopic level. The coefficient k dependent on the EIT/HIT ratio and on the stored energy (ΔW = Wtotal - Welastic) is a measure of the material reaction to the loading and the deformation of tissue.

  14. 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.

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

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

    PubMed

    Liu, Yuelian; Wu, Gang; de Groot, Klaas

    2010-10-06

    The repair of critical-sized bone defects is still challenging in the fields of implantology, maxillofacial surgery and orthopaedics. Current therapies such as autografts and allografts are associated with various limitations. Cytokine-based bone tissue engineering has been attracting increasing attention. Bone-inducing agents have been locally injected to stimulate the native bone-formation activity, but without much success. The reason is that these drugs must be delivered slowly and at a low concentration to be effective. This then mimics the natural method of cytokine release. For this purpose, a suitable vehicle was developed, the so-called biomimetic coating, which can be deposited on metal implants as well as on biomaterials. Materials that are currently used to fill bony defects cannot by themselves trigger bone formation. Therefore, biological functionalization of such materials by the biomimetic method resulted in a novel biomimetic coating onto different biomaterials. Bone morphogenetic protein 2 (BMP-2)-incorporated biomimetic coating can be a solution for a large bone defect repair in the fields of dental implantology, maxillofacial surgery and orthopaedics. Here, we review the performance of the biomimetic coating both in vitro and in vivo.

  17. Rad GTPase is essential for the regulation of bone density and bone marrow adipose tissue in mice.

    PubMed

    Withers, Catherine N; Brown, Drew M; Byiringiro, Innocent; Allen, Matthew R; Condon, Keith W; Satin, Jonathan; Andres, Douglas A

    2017-10-01

    The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca 2+ channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad. Microarray analysis revealed that canonical osteogenic gene expression (Runx2, osterix, etc.) is not altered in Rad -/- calvarial osteoblasts; instead robust up-regulation of matrix Gla protein (MGP, +11-fold), an inhibitor of extracellular matrix mineralization and a protein secreted during adipocyte differentiation, was observed. Strikingly, Rad deficiency also resulted in significantly higher marrow adipose tissue levels in vivo and promoted spontaneous in vitro adipogenesis of primary calvarial osteoblasts. Adipogenic differentiation of wildtype calvarial osteoblasts resulted in the loss of endogenous Rad protein, further supporting a role for Rad in the control of BMAT levels. These findings reveal a novel in vivo function for Rad and establish a role for Rad signaling in the complex physiological control of skeletal homeostasis and bone marrow adiposity. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Electrospun PCL/gelatin composite nanofiber structures for effective guided bone regeneration membranes.

    PubMed

    Ren, Ke; Wang, Yi; Sun, Tao; Yue, Wen; Zhang, Hongyu

    2017-09-01

    Guided bone regeneration (GBR) membranes have been proved of great benefit for bone tissue engineering due to the improvement of cell attachment and proliferation. To develop GBR membranes with better biocompatibility and more proper degradation ability, here we fabricated polycaprolactone (PCL, polymer)/gelatin (protein) hybrid nanofibrous GBR membranes via electrospinning, followed by crosslinking with genipin. Acetic acid (HAc) was utilized to resolve the phase separation of PCL and gelatin, therefore homogeneous PCL/gelatin hybrid nanofibers with different ratios were successfully prepared. FTIR, XPS, TGA, DSC results proved that the proportion of PCL and gelatin in the as-spun nanofiber membranes could be simply adjusted by changing the weight ratio of PCL and gelatin in the spinning solution. SEM and AFM images demonstrated that all the nanofibers possessed uniform and smooth structures both in two dimension (2D) and three dimension (3D). The mechanical tests showed that these nanofibers exhibited appropriate tensile and strength properties, which were suitable for bone tissue engineering. CCK-8 and SEM images revealed that all the membranes were biocompatible to MC3T3-e1 cells. In addition, the in vitro osteogenesis characterizations, alizarin red in normal medium and osteogenesis medium, indicated that the nanofibers could promote bone formation. Therefore, all these results could suggest that our design of electrospun polymer/protein nanofiber membranes was effective for guided bone regeneration. Copyright © 2017. Published by Elsevier B.V.

  19. Exercise-Induced Changes in the Cortical Bone of Growing Mice Are Bone and Gender Specific

    PubMed Central

    Wallace, Joseph M.; Rajachar, Rupak M.; Allen, Matthew R.; Bloomfield, Susan A.; Robey, Pamela G.; Young, Marian F.; Kohn, David H.

    2009-01-01

    Fracture risk and mechanical competence of bone are functions of bone mass and tissue quality, which in turn are dependent on the bone’s mechanical environment. Male mice have a greater response to non weight-bearing exercise than females, resulting in larger, stronger bones compared with control animals. The aim of this study was to test the hypothesis that short-term weight-bearing running during growth (21 days starting at 8 weeks of age; 30 minutes/day; 12 meters/minute; 5° incline; 7 days/week) would similarly have a greater impact on cross sectional geometry and mechanical competence in the femora and tibiae of male mice versus females. Based on the orientation of the legs during running and the proximity of the tibia to the point of impact, this response was hypothesized to be greatest in the tibia. Exercise-related changes relative to controls were assayed by four-point bending tests, while volumetric bone mineral density and cross-sectional geometry were also assessed. The response to running was bone and gender-specific, with male tibiae demonstrating the greatest effects. In male tibiae, periosteal perimeter, endocortical perimeter, cortical area, medial-lateral width and bending moment of inertia increased versus control mice suggesting that while growth is occurring in these mice between 8 and 11 weeks of age, exercise accelerated this growth resulting in a greater increase in bone tissue over the 3 weeks of the study. Exercise increased tissue-level strain-to-failure and structural post-yield deformation in the male tibiae, but these post-yield benefits came at the expense of decreased yield deformation, structural and tissue-level yield strength and tissue-level ultimate strength. These results suggest that exercise superimposed upon growth accelerated growth-related increases in tibial cross-sectional dimensions. Exercise also influenced the quality of this forming bone, significantly impacting structural and tissue-level mechanical properties

  20. 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.

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

    PubMed Central

    Verboket, René; 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. PMID:25802865

  2. Bone tissue engineering with a collagen–hydroxyapatite scaffold and culture expanded bone marrow stromal cells

    PubMed Central

    Villa, Max M.; Wang, Liping; Huang, Jianping; Rowe, David W.; Wei, Mei

    2015-01-01

    Osteoprogenitor cells combined with supportive biomaterials represent a promising approach to advance the standard of care for bone grafting procedures. However, this approach faces challenges, including inconsistent bone formation, cell survival in the implant, and appropriate biomaterial degradation. We have developed a collagen–hydroxyapatite (HA) scaffold that supports consistent osteogenesis by donor derived osteoprogenitors, and is more easily degraded than a pure ceramic scaffold. Herein, the material properties are characterized as well as cell attachment, viability, and progenitor distribution in vitro. Furthermore, we examined the biological performance in vivo in a critical-size mouse calvarial defect. To aid in the evaluation of the in-house collagen–HA scaffold, the in vivo performance was compared with a commercial collagen–HA scaffold (Healos®, Depuy). The in-house collagen–HA scaffold supported consistent bone formation by predominantly donor-derived osteoblasts, nearly completely filling a 3.5 mm calvarial defect with bone in all samples (n=5) after 3 weeks of implantation. In terms of bone formation and donor cell retention at 3 weeks postimplantation, no statistical difference was found between the in-house and commercial scaffold following quantitative histomorphometry. The collagen–HA scaffold presented here is an open and well-defined platform that supports robust bone formation and should facilitate the further development of collagen–hydroxyapatite biomaterials for bone tissue engineering. PMID:24909953

  3. Dentoalveolar growth inhibition induced by bone denudation on palates: a study of two isolated cleft palates with asymmetric scar tissue distribution.

    PubMed

    Ishikawa, H; Iwasaki, H; Tsukada, H; Chu, S; Nakamura, S; Yamamoto, K

    1999-09-01

    This report presents two cases of isolated cleft palate with asymmetric distribution of postsurgical scar tissue determined by laser Doppler flowmetry. To determine the effect of mucoperiosteal denudation of the bone on maxillary alveolar growth, the analysis of dentoalveolar structures compared the affected side to the unaffected side of each case. Two Japanese girls with isolated cleft palates were examined. Both subjects had undergone pushback operations (a modified version of the procedure of Wardill) for palatal repair at 18 months of age. Palatal blood flow was examined by laser Doppler flowmetry when the girls were 12 years old to determine the extent of postsurgical scar tissue over the denuded bone. To analyze the maxillary dentoalveolar structures three dimensionally, the whole surface of the upper dental cast was measured and recorded by an optical measuring device when the girls were 7 years old. Analysis via flowmetry showed that the palatal scar tissue area was limited to the anterior tooth region on the right (unaffected) side but extended posteriorly to the premolar region on the left (affected) side in both subjects. The two girls had similar dentoalveolar structures, with the dental and alveolar arches deflected lingually at the deciduous molar area on the affected side. There were no differences in the buccolingual inclination of deciduous molars or in the vertical growth of the alveolar processes between the affected and unaffected sides. In both girls, bone denudation in the premolar region appeared to result in less than 3 mm of displacement of the teeth palatally, with no change in lingual inclination. Any effects of scar tissue on the vertical development of the alveolus were not substantiated.

  4. Engineering complex orthopaedic tissues via strategic biomimicry.

    PubMed

    Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

    2015-03-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  5. Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

    PubMed Central

    Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

    2014-01-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  6. A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

    PubMed Central

    Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

    2016-01-01

    3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds. PMID:26758780

  7. A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair.

    PubMed

    Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

    2016-02-12

    3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

  8. A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

    NASA Astrophysics Data System (ADS)

    Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

    2016-02-01

    3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

  9. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, J.W.

    1995-05-09

    A device is described for stimulating bone tissue by applying a low level alternating current signal directly to the patient`s skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures. 5 figs.

  10. Three dimensional structure of the distal condyles of the third metacarpal bone of the horse.

    PubMed

    Boyde, A; Haroon, Y; Jones, S J; Riggs, C M

    1999-03-01

    This study examined the three-dimensional (3D) microarchitecture of regions of the equine third metacarpal bone (McIII) commonly involved in distal condylar fractures. Limbs were obtained from Thoroughbred horses (neonates to age 24 years) destroyed for inoperable fractures and a variety of other conditions. Beams, blocks and sections were cut in the principal axes, some embedded in PMMA and others examined unembedded. Several methods were used to study the 3D structure, including conventional and confocal optical microscopy, scanning electron microscopy (SEM) and radiography. The mineralised articular cartilage tends to cleave in the sagittal plane. Proximal to the subchondral bone, the main trabeculae are robust plates running in the sagittal direction with less significant mediolateral connections. Small blood vessel canals lie inside the sagittal plates. This structure gives maximum strength and protection in the sagittal plane in which the bone rotates, but offers minimal resistance to fracture propagation in this plane. The anatomical course of the common distal condylar fractures of the third metacarpal bones can be explained by underlying anisotropic structural features of the mineralised tissues.

  11. Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

    PubMed

    Chen, Guobao; Lv, Yonggang

    2015-01-01

    Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

  12. Bone scaffolds with homogeneous and discrete gradient mechanical properties.

    PubMed

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

    2013-01-01

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

  13. Applied Induced Pluripotent Stem Cells in Combination With Biomaterials in Bone Tissue Engineering.

    PubMed

    Ardeshirylajimi, Abdolreza

    2017-10-01

    Due to increasing of the orthopedic lesions and fractures in the world and limitation of current treatment methods, researchers, and surgeons paid attention to the new treatment ways especially to tissue engineering and regenerative medicine. Innovation in stem cells and biomaterials accelerate during the last decade as two main important parts of the tissue engineering. Recently, induced pluripotent stem cells (iPSCs) introduced as cells with highly proliferation and differentiation potentials that hold great promising features for used in tissue engineering and regenerative medicine. As another main part of tissue engineering, synthetic, and natural polymers have been shown daily grow up in number to increase and improve the grade of biopolymers that could be used as scaffold with or without stem cells for implantation. One of the developed areas of tissue engineering is bone tissue engineering; the aim of this review is present studies were done in the field of bone tissue engineering while used iPSCs in combination with natural and synthetic biomaterials. J. Cell. Biochem. 118: 3034-3042, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Carbon nanotubes: their potential and pitfalls for bone tissue regeneration and engineering.

    PubMed

    Newman, Peter; Minett, Andrew; Ellis-Behnke, Rutledge; Zreiqat, Hala

    2013-11-01

    The extracellular environment which supports cell life is composed of a hierarchy of maintenance, force and regulatory systems which integrate from the nano- through to macroscale. For this reason, strategies to recreate cell supporting environments have been investigating the use of nanocomposite biomaterials. Here, we review the use of carbon nanotubes as part of a bottom-up approach for use in bone tissue engineering. We evaluate the properties of carbon nanotubes in the context of synthetic tissue substrates and contrast them with the nanoscale features of the extracellular environment. Key studies are evaluated with an emphasis on understanding the mechanisms through which carbon nanotubes interact with biological systems. This includes an examination of how the different properties of carbon nanotubes affect tissue growth, how these properties and variation to them might be leveraged in regenerative tissue therapies and how impurities or contaminates affect their toxicity and biological interaction. In this comprehensive review, the authors describe the status and potential applications of carbon nanotubes in bone tissue engineering. © 2013.

  15. Bioglass® 45S5-based composites for bone tissue engineering and functional applications.

    PubMed

    Rizwan, M; Hamdi, M; Basirun, W J

    2017-11-01

    Bioglass® 45S5 (BG) has an outstanding ability to bond with bones and soft tissues, but its application as a load-bearing scaffold material is restricted due to its inherent brittleness. BG-based composites combine the amazing biological and bioactive characteristics of BG with structural and functional features of other materials. This article reviews the composites of Bioglass ® in combination with metals, ceramics and polymers for a wide range of potential applications from bone scaffolds to nerve regeneration. Bioglass ® also possesses angiogenic and antibacterial properties in addition to its very high bioactivity; hence, composite materials developed for these applications are also discussed. BG-based composites with polymer matrices have been developed for a wide variety of soft tissue engineering. This review focuses on the research that suggests the suitability of BG-based composites as a scaffold material for hard and soft tissues engineering. Composite production techniques have a direct influence on the bioactivity and mechanical behavior of scaffolds. A detailed discussion of the bioactivity, in vitro and in vivo biocompatibility and biodegradation is presented as a function of materials and its processing techniques. Finally, an outlook for future research is also proposed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3197-3223, 2017. © 2017 Wiley Periodicals, Inc.

  16. Activity vs. rest in the treatment of bone, soft tissue and joint injuries.

    PubMed

    Buckwalter, J A

    1995-01-01

    One of the most important advances in the treatment of musculoskeletal injuries has come from understanding that controlled early resumption of activity can promote restoration of function, and that treatment of injuries with prolonged rest may delay recovery and adversely affect normal tissues. In the last decade of the nineteenth century two widely respected orthopaedists with extensive clinical experience strongly advocated opposing treatments of musculoskeletal injuries. Hugh Owen Thomas in Liverpool believed that enforced, uninterrupted prolonged rest produced the best results. He noted that movement of injured tissues increased inflammation, and that, "It would indeed be as reasonable to attempt to cure a fever patient by kicking him out of bed, as to benefit joint disease by a wriggling at the articulation." Just Lucas-Championnier in Paris took the opposite position. He argued that early controlled active motion accelerated restoration of function, although he noted that mobility had to be given in limited doses. In general, Thomas' views met with greater acceptance in the early part of this century, but experimental studies of the last several decades generally support Lucas-Championneir. They confirm and help explain the deleterious effects of prolonged rest and the beneficial effects of activity on the musculoskeletal tissues. They have shown that maintenance of normal bone, tendon and ligament, articular cartilage and muscle structure and composition require repetitive use, and that changes in the patterns of tissue loading can strengthen or weaken normal tissues. Although all the musculoskeletal tissues can respond to repetitive loading, they vary in the magnitude and type of response to specific patterns of activity. Furthermore, their responsiveness may decline with increasing age. Skeletal muscle and bone demonstrate the most apparent response to changes in activity in individuals of any age. Cartilage and dense fibrous tissues also can respond to

  17. Bone and Soft Tissue Response in Bone-Level Implants Restored with Platform Switching: A 5-Year Clinical Prospective Study.

    PubMed

    Lago, Laura; da Silva, Luis; Gude, Francisco; Rilo, Benito

    The aim of this prospective study was to evaluate radiographic levels of peri-implant bone crest as well as soft tissue response, papilla height, and buccal mucosa recession, in bone-level implants restored with platform switching after 1-year and 5-year follow-ups. This prospective study called for the placement of 59 implants to obtain a target of 90% power. To compensate for possible dropouts, the sample size was adjusted to 67 implants. To assess marginal bone level changes, periapical radiographs were taken at baseline, 1 year, and 5 years after the definitive restorations. Peri-implant soft tissue modifications were evaluated by performing a photographic sequence at 15 days, 1 year, and 5 years after implant restoration. Parameters measured were: (1) distance from the tip of the papilla to the contact point and (2) apicocoronal crown length. A one-way analysis of variance (ANOVA rank test) was used to compare quantitative data among the three time points studied. Mean marginal bone level changes were as follows: -0.06 ± 0.32 mm from baseline to 1 year, -0.23 ± 0.38 mm from 1 to 5 years, and -0.28 ± 0.45 mm from baseline to 5 years. In bone-level outcomes, no statistically significant differences were found between baseline and 1 year, while the mean differences between 1 and 5 years and baseline and 5 years showed statistically significant differences. In the soft tissue analysis, the distance from the tip of the papilla to the contact point showed the following values: baseline, 2.08 mm; 1 year, 1.54 mm; 5 years, 1.31 mm. No statistically significant differences were found between baseline and 1 year, whereas statistically significant differences between 1 and 5 years and baseline and 5 years were found. Apicocoronal crown length measurements showed the following values: baseline, 9.44 mm; 1 year, 9.28 mm; 5 years, 9.81 mm. No significant differences were found between times studied. This prospective clinical study of 67 bone-level implants restored

  18. 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.

  19. A novel injectable temperature-sensitive zinc doped chitosan/β-glycerophosphate hydrogel for bone tissue engineering.

    PubMed

    Niranjan, Ramesh; Koushik, Chandru; Saravanan, Sekaran; Moorthi, Ambigapathi; Vairamani, Mariappanadar; Selvamurugan, Nagarajan

    2013-03-01

    Hydrogels are hydrophilic polymers that have a wide range of biomedical applications including bone tissue engineering. In this study we report preparation and characterization of a thermosensitive hydrogel (Zn-CS/β-GP) containing zinc (Zn), chitosan (CS) and beta-glycerophosphate (β-GP) for bone tissue engineering. The prepared hydrogel exhibited a liquid state at room temperature and turned into a gel at body temperature. The hydrogel was characterized by SEM, EDX, XRD, FT-IR and swelling studies. The hydrogel enhanced antibacterial activity and promoted osteoblast differentiation. Thus, we suggest that the Zn-CS/β-GP hydrogel could have potential impact as an injectable in situ forming scaffold for bone tissue engineering applications. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Rancitelli, Davide; Grossi, Giovanni Battista; Herford, Alan Scott

    2016-01-01

    The reconstruction of the atrophic alveolar ridges for implant placement is today a common procedure in dentistry daily practice. The surgical reconstruction provides for the optimization of the supporting bone for the implants and a restoration of the amount of keratinized gingiva for esthetic and functional reasons. In the past, tissue regeneration has been performed with autogenous bone and free gingival or connective tissue grafts. Nowadays, bone substitutes and specific collagen matrix allow for a complete restoration of the atrophic ridge without invasive harvesting procedures. A maxillary reconstruction of an atrophic ridge by means of tissue substitutes and its histological features are then presented. PMID:27022489

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

    PubMed

    Maiorana, Carlo; Beretta, Mario; Rancitelli, Davide; Grossi, Giovanni Battista; Cicciù, Marco; Herford, Alan Scott

    2016-01-01

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

  3. Coupled Analysis of In Vitro and Histology Tissue Samples to Quantify Structure-Function Relationship

    PubMed Central

    Acar, Evrim; Plopper, George E.; Yener, Bülent

    2012-01-01

    The structure/function relationship is fundamental to our understanding of biological systems at all levels, and drives most, if not all, techniques for detecting, diagnosing, and treating disease. However, at the tissue level of biological complexity we encounter a gap in the structure/function relationship: having accumulated an extraordinary amount of detailed information about biological tissues at the cellular and subcellular level, we cannot assemble it in a way that explains the correspondingly complex biological functions these structures perform. To help close this information gap we define here several quantitative temperospatial features that link tissue structure to its corresponding biological function. Both histological images of human tissue samples and fluorescence images of three-dimensional cultures of human cells are used to compare the accuracy of in vitro culture models with their corresponding human tissues. To the best of our knowledge, there is no prior work on a quantitative comparison of histology and in vitro samples. Features are calculated from graph theoretical representations of tissue structures and the data are analyzed in the form of matrices and higher-order tensors using matrix and tensor factorization methods, with a goal of differentiating between cancerous and healthy states of brain, breast, and bone tissues. We also show that our techniques can differentiate between the structural organization of native tissues and their corresponding in vitro engineered cell culture models. PMID:22479315

  4. Scaffold Design for Bone Regeneration

    PubMed Central

    Polo-Corrales, Liliana; Latorre-Esteves, Magda; Ramirez-Vick, Jaime E.

    2014-01-01

    The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues. PMID:24730250

  5. Pre-augmentation soft tissue expansion improves scaffold-based vertical bone regeneration - a randomized study in dogs.

    PubMed

    Kaner, Doğan; Zhao, Han; Arnold, Wolfgang; Terheyden, Hendrik; Friedmann, Anton

    2017-06-01

    Soft tissue (ST) dehiscence with graft exposure is a frequent complication of vertical augmentation. Flap dehiscence is caused by failure to achieve tension-free primary wound closure and by the impairment of flap microcirculation due to surgical trauma. Soft tissue expansion (STE) increases ST quality and quantity prior to reconstructive surgery. We hypothesized that flap preconditioning using STE would reduce the incidence of ST complications after bone augmentation and that optimized ST healing would improve the outcome of bone regeneration. Self-filling tissue expanders were implanted in mandibular bone defects in ten beagle dogs. After expansion, alloplastic scaffolds were placed for vertical bone augmentation in STE sites and in control sites without STE pre-treatment. ST flap microcirculation was analysed using laser Doppler flowmetry. The incidence of graft exposures was evaluated after 2 weeks. Bone formation was assessed after 2 months, using histomorphometry and immunohistochemistry. Test sites showed significantly less impairment of perfusion and faster recovery of microcirculation after bone augmentation. Furthermore, no flap dehiscences occurred in STE sites. Bone regeneration was found in both groups; however, significantly greater formation of new bone was detected in test sites with preceding STE. Preconditioning using STE improved ST healing and bone formation after vertical augmentation. The combination of STE and the subsequent placement of alloplastic scaffolds may facilitate the reconstruction of severe bone defects. © 2016 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.

  6. Remodeling in bone without osteocytes: Billfish challenge bone structure–function paradigms

    PubMed Central

    Atkins, Ayelet; Dean, Mason N.; Habegger, Maria Laura; Motta, Phillip J.; Ofer, Lior; Repp, Felix; Shipov, Anna; Weiner, Steve; Currey, John D.; Shahar, Ron

    2014-01-01

    A remarkable property of tetrapod bone is its ability to detect and remodel areas where damage has accumulated through prolonged use. This process, believed vital to the long-term health of bone, is considered to be initiated and orchestrated by osteocytes, cells within the bone matrix. It is therefore surprising that most extant fishes (neoteleosts) lack osteocytes, suggesting their bones are not constantly repaired, although many species exhibit long lives and high activity levels, factors that should induce considerable fatigue damage with time. Here, we show evidence for active and intense remodeling occurring in the anosteocytic, elongated rostral bones of billfishes (e.g., swordfish, marlins). Despite lacking osteocytes, this tissue exhibits a striking resemblance to the mature bone of large mammals, bearing structural features (overlapping secondary osteons) indicating intensive tissue repair, particularly in areas where high loads are expected. Billfish osteons are an order of magnitude smaller in diameter than mammalian osteons, however, implying that the nature of damage in this bone may be different. Whereas billfish bone material is as stiff as mammalian bone (unlike the bone of other fishes), it is able to withstand much greater strains (relative deformations) before failing. Our data show that fish bone can exhibit far more complex structure and physiology than previously known, and is apparently capable of localized repair even without the osteocytes believed essential for this process. These findings challenge the unique and primary role of osteocytes in bone remodeling, a basic tenet of bone biology, raising the possibility of an alternative mechanism driving this process. PMID:25331870

  7. Icariin: does it have an osteoinductive potential for bone tissue engineering?

    PubMed

    Zhang, Xin; Liu, Tie; Huang, Yuanliang; Wismeijer, Daniel; Liu, Yuelian

    2014-04-01

    Traditional Chinese medicines have been recommended for bone regeneration and repair for thousands of years. Currently, the Herba Epimedii and its multi-component formulation are the attractive native herbs for the treatment of osteoporosis. Icariin, a typical flavonol glycoside, is considered to be the main active ingredient of the Herba Epimedii from which icariin has been successfully extracted. Most interestingly, it has been reported that icariin can be delivered locally by biomaterials and that it has an osteoinductive potential for bone tissue engineering. This review focuses on the performance of icariin in bone tissue engineering and on blending the information from icariin with the current knowledge relevant to molecular mechanisms and signal pathways. The osteoinductive potential of icariin could be attributed to its multiple functions in the musculoskeletal system which is involved in the regulation of multiple signaling pathways in anti-osteoporosis, osteogenesis, anti-osteoclastogenesis, chondrogenesis, angiogenesis, and anti-inflammation. The osteoinductive potential and the low price of icariin make it a very attractive candidate as a substitute of osteoinductive protein-bone morphogenetic proteins (BMPs), or as a promoter for enhancing the therapeutic effects of BMPs. However, the effectiveness of the local delivery of icariin needs to be investigated further. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Optimization of scaffold design for bone tissue engineering: A computational and experimental study.

    PubMed

    Dias, Marta R; Guedes, José M; Flanagan, Colleen L; Hollister, Scott J; Fernandes, Paulo R

    2014-04-01

    In bone tissue engineering, the scaffold has not only to allow the diffusion of cells, nutrients and oxygen but also provide adequate mechanical support. One way to ensure the scaffold has the right properties is to use computational tools to design such a scaffold coupled with additive manufacturing to build the scaffolds to the resulting optimized design specifications. In this study a topology optimization algorithm is proposed as a technique to design scaffolds that meet specific requirements for mass transport and mechanical load bearing. Several micro-structures obtained computationally are presented. Designed scaffolds were then built using selective laser sintering and the actual features of the fabricated scaffolds were measured and compared to the designed values. It was possible to obtain scaffolds with an internal geometry that reasonably matched the computational design (within 14% of porosity target, 40% for strut size and 55% for throat size in the building direction and 15% for strut size and 17% for throat size perpendicular to the building direction). These results support the use of these kind of computational algorithms to design optimized scaffolds with specific target properties and confirm the value of these techniques for bone tissue engineering. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

  9. Tissue engineering for lateral ridge augmentation with recombinant human bone morphogenetic protein 2 combination therapy: a case report.

    PubMed

    Mandelaris, George A; Spagnoli, Daniel B; Rosenfeld, Alan L; McKee, James; Lu, Mei

    2015-01-01

    This case report describes a tissue-engineered reconstruction with recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ ACS) + cancellous allograft and space maintenance via Medpor Contain mesh in the treatment of a patient requiring maxillary and mandibular horizontal ridge augmentation to enable implant placement. The patient underwent a previously unsuccessful corticocancellous bone graft at these sites. Multiple and contiguous sites in the maxilla and in the mandibular anterior, demonstrating advanced lateral ridge deficiencies, were managed using a tissue engineering approach as an alternative to autogenous bone harvesting. Four maxillary and three mandibular implants were placed 9 and 10 months, respectively, after tissue engineering reconstruction, and all were functioning successfully after 24 months of follow-up. Histomorphometric analysis of a bone core obtained at the time of the maxillary implant placement demonstrated a mean of 76.1% new vital bone formation, 22.2% marrow/cells, and 1.7% residual graft tissue. Tissue engineering for lateral ridge augmentation with combination therapy requires further research to determine predictability and limitations.

  10. The functional activity of bone tissue cells under space flight conditions.

    NASA Astrophysics Data System (ADS)

    Rodionova, N. V.; Polkovenko, O. V.; Oganov, V. S.; Nesterenko, O. N.

    The space flight conditions affect considerably the state of bone tissue leading to the development of osteoporosis and osteopenia Many aspects of reactions of bone tissue cells still remain unclear until now With the use of electron microscopy we studied the samples gathered from the femoral bone epiphyses and metaphyses of rats flown on board the space laboratory Spacelab -- 2 during 2 weeks It was established that under microgravity conditions there occur remodelling processes in a spongy bone related with a deficit of support load In this work the main attention is focused on studying the ultrastructure of osteogenetic cells and osteoclasts The degree of differentiation and functional state are evaluated according to the degree of development of organelles for specific biosynthesis rough endoplasmic reticulum RER Golgy complex GC as well as the state of mitochondria and cell nucleus As compared with a synchronous control the population of osteogenetic cells from zones of bone reconstruction shows a decrease in the number of functionally active forms We can judge of this from the reduction of a specific volume of RER GC mitochondria in osteoblasts RER loses architectonics typical for osteoblasts and as against the control is represented by short narrow canaliculi distributed throughout the cytoplasm some canals disintegrate GC is slightly pronounced mitochondria become smaller in size and acquire an optically dark matrix These phenomena are supposed to be associated with the desorganization of microtubules and

  11. Calcium phosphate compatible bone cement: Characterization, bonding properties and tissue response

    NASA Astrophysics Data System (ADS)

    Roemhildt, Maria Lynn

    A novel, inorganic, bone cement, containing calcium phosphate, developed for implant fixation was evaluated. Setting properties were determined over a range of temperatures. The flow of the cement was greatly increased by application of vibration. Changes in the cement during hydration and aging were evaluated. Compressive strength of the cement over time was studied under simulated physiological conditions from 1 hour to 1 year after setting. After 1 day, this cement had equivalent compressive strength to commercially used PMMA cement. The strength was found to increase over 1 month and high strength was maintained up to 1 year. The shear strength of the cement-metal interface was studied in vitro using a pull-out test. Prepared specimens were stored under physiological conditions and tested at 4 hours, 24 hours, and 60 days. Comparable interfacial shear strength values were found at 4 hours, 24 hours and 60 days for the experimental cement and were not significantly different from values obtained for PMMA cement. In vivo tissue response was evaluated after cement implantation in the femoral medullary canal in canines. Tissue response and bonding at the cement-bone interface were evaluated at 2, 6, and 12 weeks. Cortical bone was found in direct contact with the OC-cement and was healthy. The strength of the cement-bone interface, measured using a push-out test, was significantly higher for the experimental cement than for commercial PMMA bone cement.

  12. Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

    NASA Astrophysics Data System (ADS)

    Ross, Ryan D.; Cole, Lisa E.; Roeder, Ryan K.

    2012-10-01

    Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate ( l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

  13. Perspectives on the role of nanotechnology in bone tissue engineering.

    PubMed

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

    2013-01-01

    This review surveys new developments in bone tissue engineering, specifically focusing on the promising role of nanotechnology and describes future avenues of research. 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 nanolevel internal surfaces of scaffolds are examined followed by an evaluation of techniques using scaffolds as a vehicle for local drug delivery to promote bone regeneration/integration and methods of seeding cells into the scaffold. Through a review of the state of the field, critical questions are posed to guide future research toward producing materials and therapies to bring state-of-the-art technology to clinical settings. 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. Published by Elsevier Ltd.

  14. The connection between cellular mechanoregulation and tissue patterns during bone healing.

    PubMed

    Repp, Felix; Vetter, Andreas; Duda, Georg N; Weinkamer, Richard

    2015-09-01

    The formation of different tissues in the callus during secondary bone healing is at least partly influenced by mechanical stimuli. We use computer simulations to test the consequences of different hypotheses of the mechanoregulation at the cellular level on the patterns of tissues formed during healing. The computational study is based on an experiment on sheep, where after a tibial osteotomy, histological sections were harvested at different time points. In the simulations, we used a recently proposed basic phenomenological model, which allows ossification to occur either via endochondral or intramembranous ossification, but tries otherwise to employ a minimal number of simulation parameters. The model was extended to consider also the possibility of bone resorption and consequently allowing a description of the full healing progression till the restoration of the cortex. Specifically, we investigated how three changes in the mechanoregulation influence the resulting tissue patterns: (1) a time delay between stimulation of the cell and the formation of the tissue, (2) a variable mechanosensitivity of the cells, and (3) an independence of long time intervals of the soft tissue maturation from the mechanical stimulus. For all three scenarios, our simulations do not show qualitative differences in the time development of the tissue patterns. Largest differences were observed in the intermediate phases of healing in the amount and location of the cartilage. Interestingly, the course of healing was virtually unaltered in case of scenario (3) where tissue maturation proceeded independent of mechanical stimulation.

  15. The effects of corrosive substances on human bone, teeth, hair, nails, and soft tissue.

    PubMed

    Hartnett, Kristen M; Fulginiti, Laura C; Di Modica, Frank

    2011-07-01

    This research investigates the effects of household chemicals on human tissues. Five different human tissues (bone, tooth, hair, fingernails, and skin/muscle/fat) were immersed into six different corrosive agents. These agents consisted of hydrochloric acid, sulfuric acid, lye, bleach, organic septic cleaner, and Coca-Cola(®) soda. Tap water was used as a control. Tissue samples were cut to consistent sizes and submerged in the corrosive liquids. Over time, the appearance, consistency, and weight were documented. Hydrochloric acid was the most destructive agent in this study, consuming most tissues within 24 h. Sulfuric acid was the second most destructive agent in this study. Bleach, lye, and cola had no structural effects on the hard tissues of the body, but did alter the appearance or integrity of the hair, nails, or flesh in some way. The organic septic cleaner and tap water had no effect on any of the human tissue tested during the timeframe of the study. 2011 American Academy of Forensic Sciences. Published 2011. This article is a U.S. Government work and is in the public domain in the U.S.A.

  16. 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.

  17. Biofunctional Ionic-Doped Calcium Phosphates: Silk Fibroin Composites for Bone Tissue Engineering Scaffolding.

    PubMed

    Pina, S; Canadas, R F; Jiménez, G; Perán, M; Marchal, J A; Reis, R L; Oliveira, J M

    2017-01-01

    The treatment and regeneration of bone defects caused by traumatism or diseases have not been completely addressed by current therapies. Lately, advanced tools and technologies have been successfully developed for bone tissue regeneration. Functional scaffolding materials such as biopolymers and bioresorbable fillers have gained particular attention, owing to their ability to promote cell adhesion, proliferation, and extracellular matrix production, which promote new bone growth. Here, we present novel biofunctional scaffolds for bone regeneration composed of silk fibroin (SF) and β-tricalcium phosphate (β-TCP) and incorporating Sr, Zn, and Mn, which were successfully developed using salt-leaching followed by a freeze-drying technique. The scaffolds presented a suitable pore size, porosity, and high interconnectivity, adequate for promoting cell attachment and proliferation. The degradation behavior and compressive mechanical strengths showed that SF/ionic-doped TCP scaffolds exhibit improved characteristics for bone tissue engineering when compared with SF scaffolds alone. The in vitro bioactivity assays using a simulated body fluid showed the growth of an apatite layer. Furthermore, in vitro assays using human adipose-derived stem cells presented different effects on cell proliferation/differentiation when varying the doping agents in the biofunctional scaffolds. The incorporation of Zn into the scaffolds led to improved proliferation, while the Sr- and Mn-doped scaffolds presented higher osteogenic potential as demonstrated by DNA quantification and alkaline phosphatase activity. The combination of Sr with Zn led to an influence on cell proliferation and osteogenesis when compared with single ions. Our results indicate that biofunctional ionic-doped composite scaffolds are good candidates for further in vivo studies on bone tissue regeneration. © 2017 S. Karger AG, Basel.

  18. Biocompatible nanocomposite scaffolds based on copolymer-grafted chitosan for bone tissue engineering with drug delivery capability.

    PubMed

    Saber-Samandari, Samaneh; Saber-Samandari, Saeed

    2017-06-01

    Significant efforts have been made to develop a suitable biocompatible scaffold for bone tissue engineering. In this work, a chitosan-graft-poly(acrylic acid-co-acrylamide)/hydroxyapatite nanocomposite scaffold was synthesized through a novel multi-step route. The prepared scaffolds were characterized for crystallinity, morphology, elemental analysis, chemical bonds, and pores size in their structure. The mechanical properties (i.e. compressive strength and elastic modulus) of the scaffolds were examined. Further, the biocompatibility of scaffolds was determined by MTT assays on HUGU cells. The result of cell culture experiments demonstrated that the prepared scaffolds have good cytocompatibility without any cytotoxicity, and with the incorporation of hydroxyapatite in their structure improves cell viability and proliferation. Finally, celecoxib as a model drug was efficiently loaded into the prepared scaffolds because of the large specific surface area. The in vitro release of the drug displayed a biphasic pattern with a low initial burst and a sustained release of up to 14days. Furthermore, different release kinetic models were employed for the description of the release process. The results suggested that the prepared cytocompatible and non-toxic nanocomposite scaffolds might be efficient implants and drug carriers in bone-tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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.

  20. Design of polymer-biopolymer-hydroxyapatite biomaterials for bone tissue engineering: Through molecular control of interfaces

    NASA Astrophysics Data System (ADS)

    Verma, Devendra

    In this dissertation, novel biomaterials are designed for bone biomaterials and bone tissue engineering applications. Novel biomaterials of hydroxyapatite with synthetic and natural polymers have been fabricated using a combination of processing routes. Initially, we investigated hydroxyapatite-polycaprolactone-polyacrylic acid composites and observed that minimal interfacial interactions between polymer and mineral led to inadequate improvement in the mechanical properties. Bioactivity experiments on these composites showed that the presence of functional groups, such as carboxylate groups, influence bioactivity of the composites. We have developed and investigated composites of hydroxyapatite with chitosan and polygalacturonic acid (PgA). Chitosan and PgA are biocompatible, biodegradable, and also electrostatically complementary to each other. This strategy led to significant improvement in mechanical properties of new composites. The nanostructure analysis using atomic force microscopy revealed a multilevel organization in these composites. Enhancement in mechanical response was attributed to stronger interfaces due to strong electrostatic interaction between oppositely charged chitosan and PgA. Further analysis using the Rietveld method showed that biopolymers have marked impact on hydroxyapatite crystal growth and also on its crystal structure. Significant changes were observed in the lattice parameters of hydroxyapatite synthesized by following biomineralization method (organics mediated mineralization). For scaffold preparation, chitosan and PgA were mixed first, and then, nano-hydroxyapatite was added. Oppositely charged polyelectrolytes, such as chitosan and PgA, spontaneously form complex upon mixing. The poly-electrolyte complex exists as nano-sized particles. Chitosan/PgA scaffolds with and without hydroxyapatite were prepared by the freeze drying method. By controlling the rate of cooling and concentration, we have produced both fibrous and sheet

  1. Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

    PubMed Central

    Maisani, Mathieu; Pezzoli, Daniele; Chassande, Olivier; Mantovani, Diego

    2017-01-01

    Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels. PMID:28634532

  2. Digital electronic bone growth stimulator

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

    Kronberg, J.W.

    1995-05-09

    A device is described for stimulating bone tissue by applying a low level alternating current signal directly to the patient`s skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated tomore » the underlying bone structures. 5 figs.« less

  3. [Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor].

    PubMed

    Zhang, Minglei; Wang, Dapeng; Yin, Ruofeng

    2015-10-06

    To explorec Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor transinfected. Rat bone marrow mesenchymal stem cells (BMSCs) was separated, using BMSCs as target cells, and then vascular endothelial growth factor (VEGF) gene was transfected. Composite bone marrow mesenchymal stem cells and cells transfected with nano-hydroxyapatite (HA)/polylactic-co-glycolic acid (PLGA). The composition of cell and scaffold was observed. The blank plasmid transfection was 39.1%, 40.1% in VEGF group. The cell adhesion and growth was found on the scaffold pore wall after 5 days, and the number of adherent cells in the nano-HA/PLGA composite scaffold material basically had no significant difference in both. Although the nano-HA/PLGA scaffold material is still not fully meet the requirements of the matrix material for bone tissue engineering, but good biocompatibility, structure is its rich microporous satisfaction in material mechanics, toughening, enhanced obviously. Composition scaffold with BMSCs transfected by VEGF plasmid, the ability of angiogenesis is promoted.

  4. Permeability study of cancellous bone and its idealised structures.

    PubMed

    Syahrom, Ardiyansyah; Abdul Kadir, Mohammed Rafiq; Harun, Muhamad Nor; Öchsner, Andreas

    2015-01-01

    Artificial bone is a suitable alternative to autografts and allografts, however their use is still limited. Though there were numerous reports on their structural properties, permeability studies of artificial bones were comparably scarce. This study focused on the development of idealised, structured models of artificial cancellous bone and compared their permeability values with bone surface area and porosity. Cancellous bones from fresh bovine femur were extracted and cleaned following an established protocol. The samples were scanned using micro-computed tomography (μCT) and three-dimensional models of the cancellous bones were reconstructed for morphology study. Seven idealised and structured cancellous bone models were then developed and fabricated via rapid prototyping technique. A test-rig was developed and permeability tests were performed on the artificial and real cancellous bones. The results showed a linear correlation between the permeability and the porosity as well as the bone surface area. The plate-like idealised structure showed a similar value of permeability to the real cancellous bones. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

  5. Intrasocket reactive soft tissue for primary closure after augmentation of extraction sites with severe bone loss before implant placement.

    PubMed

    Mardinger, Ofer; Chaushu, Gavriel; Ghelfan, Oded; Nissan, Joseph

    2009-06-01

    The normal bone resorption after tooth extraction can be significantly aggravated in the case of pre-existing severe bone loss and chronic infection. Bone augmentation procedures have been proposed, but they require adequate closure of soft tissues. We propose the use of intrasocket reactive tissue to cover extraction sites augmented by bovine bone mineral graft to promote the success of the graft procedure. The study included 24 patients with severe bone loss and chronic pathology in 27 sites. The intrasocket reactive soft tissue was elevated from the bony walls in a subperiosteal plane. Porous bovine or allograft bone mineral was placed in the extraction site without membranes, and the intrasocket reactive soft tissue was sutured over the grafting material to seal the coronal portion of the socket. Twenty-seven implants were placed 6 months after bone augmentation. Healing progressed uneventfully. Postoperative morbidity was minimal. There was no leakage or infection of the grafting material. The mean time to implant placement was 7.8 months. Supplemental augmentation was not needed. There were no implant failures. Follow-up ranged from 6 to 36 months (mean, 15 months). All implants were rehabilitated with fixed prostheses. Intrasocket reactive soft tissue can be used predictably to obtain primary closure of augmented extraction sites with severe bone loss with minimal postoperative morbidity.

  6. Production of Composite Scaffold Containing Silk Fibroin, Chitosan, and Gelatin for 3D Cell Culture and Bone Tissue Regeneration.

    PubMed

    Li, Jianqing; Wang, Qiuke; Gu, Yebo; Zhu, Yu; Chen, Liang; Chen, Yunfeng

    2017-11-08

    BACKGROUND Bone tissue engineering, a powerful tool to treat bone defects, is highly dependent on use of scaffolds. Both silk fibroin (SF) and chitosan (Cs) are biocompatible and actively studied for reconstruction of tissue engineering. Gelatin (Gel) is also widely applied in the biomedical field due to its low antigenicity and physicochemical stability. MATERIAL AND METHODS In this study, 4 different types of scaffolds were constructed - SF, SF/Cs, SF/Gel, and SF/Cs/Gel - and we compared their physical and chemical properties as well as biological characterization of these scaffolds to determine the most suitable scaffold for use in bone regeneration. First, these scaffolds were produced via chemical cross-linking method and freeze-drying technique. Next, the characterization of internal structure was studied using scanning electron microscopy and the porosity was evaluated by liquid displacement method. Then, we compared physicochemical properties such as water absorption rate and degradation property. Finally, MC3T3-E1 cells were inoculated on the scaffolds to study the biocompatibility and osteogenesis of the three-dimensional (3D) scaffolds in vitro. RESULTS The composite scaffold formed by all 3 components was the best for use in bone regeneration. CONCLUSIONS We conclude that the best scaffold among the 4 studied for MC3T3-E1 cells is our SF/Cs/Gel scaffold, suggesting a new choice for bone regeneration that can be used to treat bone defects or fractures in clinical practice.

  7. Long-term stability of peri-implant tissues after bone or soft tissue augmentation. Effect of zirconia or titanium abutments on peri-implant soft tissues. Summary and consensus statements. The 4th EAO Consensus Conference 2015.

    PubMed

    Sicilia, Alberto; Quirynen, Marc; Fontolliet, Alain; Francisco, Helena; Friedman, Anton; Linkevicius, Tomas; Lutz, Rainer; Meijer, Henny J; Rompen, Eric; Rotundo, Roberto; Schwarz, Frank; Simion, Massimo; Teughels, Wim; Wennerberg, Ann; Zuhr, Otto

    2015-09-01

    Several surgical techniques and prosthetic devices have been developed in the last decades, aiming to improve aesthetic, hygienic and functional outcomes that may affect the peri-implant tissues, such as procedures of bone and soft tissue augmentation and the use of custom-made abutments of titanium and zirconium. Three systematic reviews, based on randomized clinical trials and prospective studies covering the above reported topics were analysed, and the detected evidence was exposed to interactive experts' discussion during the group's and general assembly's meetings of the 4th EAO Consensus Conference. The results are reported using the following abbreviations: S-T: short-term evidence, M-T: medium-term evidence; L-T: long-term evidence; LE: limited evidence. Soft tissue augmentation procedures may be indicated for the increase of soft tissue thickness and keratinized tissue, the reduction of interproximal peri-implant bone loss, and the coverage of shallow peri-implant soft tissue recessions (S-T, LE), L-T is lacking. Guided bone regeneration approaches (GBR) showed efficacy when used for ridge reconstruction after the complete healing of the soft tissues (S-T & L-T), and the stability of the augmented bone may play a role in the maintenance of the soft tissue position and dimensions (LE). No significant differences were observed between titanium and zirconia abutments when evaluating probing pocket depth, bleeding on probing, marginal bone levels and mucosal recessions. Zirconia abutments were associated with more biological complications but demonstrated superiority in terms of achieving natural soft tissue colour (S-T). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

    Pina, Sandra; Oliveira, Joaquim M; Reis, Rui L

    2015-02-18

    Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Demineralized dentin matrix composite collagen material for bone tissue regeneration.

    PubMed

    Li, Jianan; Yang, Juan; Zhong, Xiaozhong; He, Fengrong; Wu, Xiongwen; Shen, Guanxin

    2013-01-01

    Demineralized dentin matrix (DDM) had been successfully used in clinics as bone repair biomaterial for many years. However, particle morphology of DDM limited it further applications. In this study, DDM and collagen were prepared to DDM composite collagen material. The surface morphology of the material was studied by scanning electron microscope (SEM). MC3T3-E1 cells responses in vitro and tissue responses in vivo by implantation of DDM composite collagen material in bone defect of rabbits were also investigated. SEM analysis showed that DDM composite collagen material evenly distributed and formed a porous scaffold. Cell culture and animal models results indicated that DDM composite collagen material was biocompatible and could support cell proliferation and differentiation. Histological evaluation showed that DDM composite collagen material exhibited good biocompatibility, biodegradability and osteoconductivity with host bone in vivo. The results suggested that DDM composite collagen material might have a significant clinical advantage and potential to be applied in bone and orthopedic surgery.

  10. Bone up: craniomandibular development and hard-tissue biomineralization in neonate mice.

    PubMed

    Thompson, Khari D; Weiss-Bilka, Holly E; McGough, Elizabeth B; Ravosa, Matthew J

    2017-10-01

    The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than previously recognized. However, the relationship between patterns of cranial bone formation and biomineralization remains incompletely understood. In four strains of mice, micro-computed tomography was used to measure tissue mineral density during perinatal development in three skull regions (calvarium, basicranium, mandible) noted for variation in loading environment, embryological origin, and ossification mode. Biomineralization levels increased during perinatal ontogeny in the mandible and calvarium, but did not increase in the basicranium. Tissue mineral density levels also varied intracranially, with density in the mandible being highest, in the basicranium intermediate, and in the calvarium lowest. Perinatal increases in, and elevated levels of, mandibular biomineralization appear related to the impending postweaning need to resist elevated masticatory stresses. Similarly, perinatal increases in calvarial biomineralization may be linked to ongoing brain expansion, which is known to stimulate sutural bone formation in this region. The lack of perinatal increase in basicranial biomineralization could be a result of earlier developmental maturity in the cranial base relative to other skull regions due to its role in supporting the brain's mass throughout ontogeny. These results suggest that biomineralization levels and age-related trajectories throughout the skull are influenced by the functional environment and ontogenetic processes affecting each region, e.g., onset of masticatory loads in the mandible, whereas variation in embryology and ossification mode may only have secondary effects on patterns of biomineralization. Knowledge of perinatal variation in tissue mineral density, and of normal cranial bone formation early in development, may benefit clinical therapies aiming to correct

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

    PubMed

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

    2013-09-01

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

  12. Differentiation of osteoclast precursors on gellan gum-based spongy-like hydrogels for bone tissue engineering.

    PubMed

    Maia, F Raquel; Musson, David S; Naot, Dorit; da Silva, Lucilia P; Bastos, Ana R; Costa, João B; Oliveira, Joaquim M; Correlo, Vitor M; Reis, Rui L; Cornish, Jillian

    2018-03-16

    Bone tissue engineering with cell-scaffold constructs has been attracting a lot of attention, in particular as a tool for the efficient guiding of new tissue formation. However, the majority of the current strategies used to evaluate novel biomaterials focus on osteoblasts and bone formation, while osteoclasts are often overlooked. Consequently, there is limited knowledge on the interaction between osteoclasts and biomaterials. In this study, the ability of spongy-like gellan gum and hydroxyapatite-reinforced gellan gum hydrogels to support osteoclastogenesis was investigated in vitro. First, the spongy-like gellan gum and hydroxyapatite-reinforced gellan gum hydrogels were characterized in terms of microstructure, water uptake and mechanical properties. Then, bone marrow cells isolated from the long bones of mice and cultured in spongy-like hydrogels were treated with 1,25-dihydroxyvitamin D3 to promote osteoclastogenesis. It was shown that the addition of HAp to spongy-like gellan gum hydrogels enables the formation of larger pores and thicker walls, promoting an increase in stiffness. Hydroxyapatite-reinforced spongy-like gellan gum hydrogels support the formation of the aggregates of tartrate-resistant acid phosphatase-stained cells and the expression of genes encoding DC-STAMP and Cathepsin K, suggesting the differentiation of bone marrow cells into pre-osteoclasts. The hydroxyapatite-reinforced spongy-like gellan gum hydrogels developed in this work show promise for future use in bone tissue scaffolding applications.

  13. Numerical simulation of fluid field and in vitro three-dimensional fabrication of tissue-engineered bones in a rotating bioreactor and in vivo implantation for repairing segmental bone defects.

    PubMed

    Song, Kedong; Wang, Hai; Zhang, Bowen; Lim, Mayasari; Liu, Yingchao; Liu, Tianqing

    2013-03-01

    In this paper, two-dimensional flow field simulation was conducted to determine shear stresses and velocity profiles for bone tissue engineering in a rotating wall vessel bioreactor (RWVB). In addition, in vitro three-dimensional fabrication of tissue-engineered bones was carried out in optimized bioreactor conditions, and in vivo implantation using fabricated bones was performed for segmental bone defects of Zelanian rabbits. The distribution of dynamic pressure, total pressure, shear stress, and velocity within the culture chamber was calculated for different scaffold locations. According to the simulation results, the dynamic pressure, velocity, and shear stress around the surface of cell-scaffold construction periodically changed at different locations of the RWVB, which could result in periodical stress stimulation for fabricated tissue constructs. However, overall shear stresses were relatively low, and the fluid velocities were uniform in the bioreactor. Our in vitro experiments showed that the number of cells cultured in the RWVB was five times higher than those cultured in a T-flask. The tissue-engineered bones grew very well in the RWVB. This study demonstrates that stress stimulation in an RWVB can be beneficial for cell/bio-derived bone constructs fabricated in an RWVB, with an application for repairing segmental bone defects.

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

    PubMed

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

    2012-10-01

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

  15. Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis.

    PubMed

    Schmidt-Bleek, Katharina; Kwee, Brian J; Mooney, David J; Duda, Georg N

    2015-08-01

    Delayed healing or nonhealing of bone is an important clinical concern. Although bone, one of the two tissues with scar-free healing capacity, heals in most cases, healing is delayed in more than 10% of clinical cases. Treatment of such delayed healing condition is often painful, risky, time consuming, and expensive. Tissue healing is a multistage regenerative process involving complex and well-orchestrated steps, which are initiated in response to injury. At best, these steps lead to scar-free tissue formation. At the onset of healing, during the inflammatory phase, stationary and attracted macrophages and other immune cells at the fracture site release cytokines in response to injury. This initial reaction to injury is followed by the recruitment, proliferation, and differentiation of mesenchymal stromal cells, synthesis of extracellular matrix proteins, angiogenesis, and finally tissue remodeling. Failure to heal is often associated with poor revascularization. Since blood vessels mediate the transport of circulating cells, oxygen, nutrients, and waste products, they appear essential for successful healing. The strategy of endogenous regeneration in a tissue such as bone is interesting to analyze since it may represent a blueprint of successful tissue formation. This review highlights the interdependency of the time cascades of inflammation, angiogenesis, and tissue regeneration. A better understanding of these inter-relations is mandatory to early identify patients at risk as well as to overcome critical clinical conditions that limit healing. Instead of purely tolerating the inflammatory phase, modulations of inflammation (immunomodulation) might represent a valid therapeutic strategy to enhance angiogenesis and foster later phases of tissue regeneration.

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

    PubMed

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

    2018-05-01

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

  17. The Effects of Obesity on Murine Cortical Bone

    NASA Astrophysics Data System (ADS)

    Martin, Sophi

    This dissertation details the effects of obesity on the mechanical properties and structure of cortical bone. Obesity is associated with greater bone mineral content that might be expected to protect against fracture, which has been observed in adults. Paradoxically however, the incidence of bone fractures has been found to increase in overweight and obese children and adolescents. Femora from adolescent and adult mice fed a high-fat diet are investigated for changes in shape, tissue structure, as well as tissue-level and whole-bone mechanical properties. Results indicate increased bone size, reduced size-independent mechanical properties, but maintained size-dependent mechanical properties. Other changes in cortical bone response to obesity are observed with advancing age. This study indicates that bone quantity and bone quality play important compensatory roles in determining fracture risk, and that fracture risk may not be lessened for adults as previously thought.

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

    PubMed

    Salguero, Laura; Saadat, Fatemeh; Sevostianov, Igor

    2014-10-17

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

  19. Fabrication of a three-dimensional β-tricalcium-phosphate/gelatin containing chitosan-based nanoparticles for sustained release of bone morphogenetic protein-2: Implication for bone tissue engineering.

    PubMed

    Bastami, Farshid; Paknejad, Zahrasadat; Jafari, Maissa; Salehi, Majid; Rezai Rad, Maryam; Khojasteh, Arash

    2017-03-01

    Fabrication of an ideal scaffold having proper composition, physical structure and able to have sustained release of growth factors still is challenging for bone tissue engineering. Current study aimed to design an appropriate three-dimensional (3-D) scaffold with suitable physical characteristics, including proper compressive strength, degradation rate, porosity, and able to sustained release of bone morphogenetic protein-2 (BMP2), for bone tissue engineering. A highly porous 3-D β-tricalcium phosphate (β-TCP) scaffolds, inside of which two perpendicular canals were created, was fabricated using foam-casting technique. Then, scaffolds were coated with gelatin layer. Next, BMP2-loaded chitosan (CS) nanoparticles were dispersed into collagen hydrogel and filled into the scaffold canals. Physical characteristics of fabricated constructs were evaluated. Moreover, the capability of given construct for bone regeneration has been evaluated in vitro in interaction with human buccal fat pad-derived stem cells (hBFPSCs). The results showed that gelatin-coated TCP scaffold with rhBMP2 delivery system not only could act as a mechanically and biologically compatible framework, but also act as an osteoinductive graft by sustained delivering of rhBMP2 in a therapeutic window for differentiation of hBFPSCs towards the osteoblast lineage. The proposed scaffold model can be suggested for delivering of cells and other growth factors such as vascular endothelial growth factor (VEGF), alone or in combination, for future investigations. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2011-05-01

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