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Sample records for bone tissue structure

  1. Remodeling of tissue-engineered bone structures in vivo.

    PubMed

    Hofmann, Sandra; Hilbe, Monika; Fajardo, Robert J; Hagenmüller, Henri; Nuss, Katja; Arras, Margarete; Müller, Ralph; von Rechenberg, Brigitte; Kaplan, David L; Merkle, Hans P; Meinel, Lorenz

    2013-09-01

    Implant design for bone regeneration is expected to be optimized when implant structures resemble the anatomical situation of the defect site. We tested the validity of this hypothesis by exploring the feasibility of generating different in vitro engineered bone-like structures originating from porous silk fibroin scaffolds decorated with RGD sequences (SF-RGD), seeded with human mesenchymal stem cells (hMSC). Scaffolds with small (106-212 μm), medium (212-300 μm), and large pore diameter ranges (300-425 μm) were seeded with hMSC and subsequently differentiated in vitro into bone-like tissue resembling initial scaffold geometries and featuring bone-like structures. Eight weeks after implantation into calvarial defects in mice, the in vitro engineered bone-like tissues had remodeled into bone featuring different proportions of woven/lamellar bone bridging the defects. Regardless of pore diameter, all implants integrated well, vascularization was advanced, and bone marrow ingrowth had started. Ultimately, in this defect model, the geometry of the in vitro generated tissue-engineered bone structure, trabecular- or plate-like, had no significant impact on the healing of the defect, owing to an efficient remodeling of its structure after implantation. PMID:23958323

  2. Remodeling of tissue-engineered bone structures in vivo

    PubMed Central

    Hofmann, Sandra; Hilbe, Monika; Fajardo, Robert J.; Hagenmüller, Henri; Nuss, Katja; Arras, Margarete; Müller, Ralph; von Rechenberg, Brigitte; Kaplan, David L.; Merkle, Hans P.; Meinel, Lorenz

    2013-01-01

    Implant design for bone regeneration is expected to be optimized when implant structures resemble the anatomical situation of the defect site. We tested the validity of this hypothesis by exploring the feasibility of generating different in vitro engineered bone-like structures originating from porous silk fibroin scaffolds decorated with RGD sequences (SF-RGD), seeded with human mesenchymal stem cells (hMSC). Scaffolds with small (106 – 212 μm), medium (212 – 300 μm) and large pore diameter ranges (300 – 425 μm) were seeded with hMSC and subsequently differentiated in vitro into bone-like tissue resembling initial scaffold geometries and featuring bone-like structures. Eight weeks after implantation into calvarial defects in mice, the in vitro engineered bone-like tissues had remodeled into bone featuring different proportions of woven/lamellar bone bridging the defects. Regardless of pore diameter all implants integrated well, vascularization was advanced and, bone marrow ingrowth had started. Ultimately, in this defect model, the geometry of the in vitro generated tissue-engineered bone structure, trabecular- or plate-like, had no significant impact on the healing of the defect, owing to an efficient remodeling of its structure after implantation. PMID:23958323

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

    PubMed Central

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

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling. PMID:26247020

  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. Composites structures for bone tissue reconstruction

    SciTech Connect

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

    2015-05-22

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

  6. Computer modelling of the structure of the cortical and trabecular bone tissue

    NASA Astrophysics Data System (ADS)

    Kolmakova, Tatyana

    2015-10-01

    The paper presents computer models of the structure of cortical and trabecular bone tissue. The model fragment of the cortical bone tissue was built based on a real image of the natural bone microstructure. The osteons and Haversian canals were directly taken into consideration. The Volkmann's canals and the orientation of the collagenous mineral fibers in the osteons and the surrounding matrix were considered indirectly. The model fragment of the trabecular bone tissue was built based on the data of structure of the real bone fragments, taking into account the orientation of the trabecules of bones, their length and thickness.

  7. [Structural features of ectopic bone-like tissue in porous hydroxyapatite blocks].

    PubMed

    Hattori, Shigetaka

    2008-06-01

    Calcium phosphate ceramics are widely used as bone substitutes because of their favorable biocompatibility and osteoconductivity. Some studies have reported that porous hydroxyapatite (HA), with its special structure, implanted at ectopic (non-bone) sites, exhibits osteoinductive activity. However, few studies have examined the detailed ultrastructure of mineralized tissue formed in biomaterials like HA. Therefore, it is important to examine whether the mineralized tissue exhibits structural characteristics of normal bone tissue. Thus, in this study, we subcutaneously implanted hydroxyapatite blocks (5 x 5 x 7 mm) into the backs of adult dogs, and performed detailed morphological examination of the bone-like tissue formed, which showed a lamellar structure. Immunohistochemical staining revealed that the matrix fibers of the bone-like tissue were mainly composed of type I collagen. The pattern of crystal deposition in matrix fibers and the structure of osteoblast-, osteocyte-, bone-lining-, and osteoclast-like cells were similar to those of normal bone tissue and osteogenic cells, respectively. These results indicate that cellular events observed in normal bone formation and remodeling occur in bone-like tissue as well, and suggest that bone-like tissue in HA blocks is very similar to bone tissue. PMID:18634458

  8. [Bone tissue engineering scaffolds].

    PubMed

    Fang, Liru; Weng, Wenjian; Shen, Ge; Han, Gaorong; Santos, J D; Du, Peiyi

    2003-03-01

    Bone tissue engineering may provide an alternative to the repairs to skeletal defects resulting from disease, trauma or surgery. Scaffold has played an important role in bone tissue engineering, which functions as the architecture for bone in growth. In this paper, the authors gave a brief introduction about the requirement of bone tissue engineering scaffold, the key of the design of scaffolds and the current research on this subject. PMID:12744187

  9. The evaluation of a synthetic long bone structure as a substitute for human tissue in gunshot experiments.

    PubMed

    Kneubuehl, B P; Thali, M J

    2003-12-17

    Our goal was to compare experimental gunshot wounds in our non-biological bone model with similarly created wounds in swine bones, and evaluate the results. The design of the synthetic (polyurethane) bone was patterned after human bone structure, with a compact outer layer covering a porous inner layer. Ordnance gelatin, as substitute bone marrow, was injected into the bone's hollow core. To simulate the periostium, the bone was covered with a layer of latex. Then the bone was embedded in gelatin used to simulate surrounding soft tissue. For comparison, fresh swine bones were also embedded in gelatin, and fired upon under the same guidelines. All gunshots were high-speed filmed. In our experimental study, gunshot wounds to swine bones, and to our synthetic, non-biological bones were compared. The results (the comparison between the biological swine bones and the non-biological model bones) in regard to the following points are absolutely equal: the loss of velocity and energy after striking bone, bone fragmentation, bullet deformation, and the penetrating wound channel. Continuing studies with our synthetic bone model will bring about an even greater understanding of the mechanisms of "bullet-bone interaction". For this reason, we have extended our variety of bone models to include other skeletal structures such as skull, spine, pelvis and flat bones for further gunshot experiments. PMID:14642718

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

    PubMed Central

    Gao, Xiang; Zhang, Xiaohong; Song, Jinlin; Xu, Xiao; Xu, Anxiu; Wang, Mengke; Xie, Bingwu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2015-01-01

    The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering. PMID:26604759

  11. Bone cement with a modified polyphosphate network structure stimulates hard tissue regeneration.

    PubMed

    Lee, Byung-Hyun; Hong, Min-Ho; Kim, Min-Chul; Kwon, Jae-Sung; Ko, Yeong-Mu; Choi, Heon-Jin; Lee, Yong-Keun

    2016-09-01

    In this study, a calcium polyphosphate cement (CpPC) consisting of basic components was investigated to assess its potential for hard tissue regeneration. The added basic components for improving the structural stability, which controlled the setting time, where the setting reaction resulted in the formation of amorphous structure with a re-constructed polyphosphate. Moreover, the characteristics were controlled by the composition, which determined the polyphosphate structure. CpPC exhibited outstanding dissolution rate compared with the common biodegradable cement, brushite cement (2.5 times). Despite high amounts of dissolution products, no significant cytotoxicity ensued. Induction of calcification in MG-63 cells treated with CpPC, the level of calcification increased with increasing CpPC dissolution rate. Induced calcification was observed also in CpPC-treated ST2 cells, in contrast with MG-63 and ST2 treated with brushite cement, for which no calcification was observed. In vivo tests using a rat calvarial defect model showed that resorbed CpPC resulted in favorable host responses and promoted bone formation. Additionally, there was a significant increase in defect closure, and new bone formation progressed from CpPC mid-sites as well as defect margins. From these results, CpPC exhibits significant potential as biodegradable bone substitute for bone regeneration. PMID:27511981

  12. [Structural mechanisms and mathematical modeling of the bone tissue damage caused by hyper-speed impact].

    PubMed

    Ishchenko, A N; Belov, N N; Gaĭdash, A A; Iugov, N T; Bashirov, R S; Afanas'eva, S A; Sinitsa, L N

    2011-03-01

    Method of computer modeling of behavior of cylindrical and lamellar bones under the hypervelocity impact is suggested. This method allows in the frame of mechanics of continuous medium to calculate the stress strain behavior and damage in bone tissues under the shock wave impact. The processes of shock correlation of steel fragments of different shape with diaphysis of cylindrical bones and flat bone of calvaria under the impact 500 m/s are studied. The given method can be used for the evaluation of damage area of bone tissue of shock wave osteoporosis under the gunshot wound. PMID:21770310

  13. Polarization-Correlation Analysis of Anisotropic Structures in Bone Tissue for the Diagnostics of Pathological Changes

    NASA Astrophysics Data System (ADS)

    Angel'Skiĭ, O. V.; Ushenko, A. G.; Burkovets, D. N.; Ushenko, Yu. A.

    2001-03-01

    A method for the correlation analysis of polarization-filtered laser images of bone tissue is considered. Its ability to visualize the bone-tissue multifractal network in its normal and pathological states is analyzed. A set of criteria for the optical diagnostics of osteoporosis is determined.

  14. 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. PMID:26926069

  15. 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

  16. 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

  17. Bone tissue incorporates in vitro gallium with a local structure similar to gallium-doped brushite.

    PubMed

    Korbas, M; Rokita, E; Meyer-Klaucke, W; Ryczek, J

    2004-01-01

    During mineral growth in rat bone-marrow stromal cell cultures, gallium follows calcium pathways. The dominant phase of the cell culture mineral constitutes the poorly crystalline hydroxyapatite (HAP). This model system mimics bone mineralization in vivo. The structural characterization of the Ga environment was performed by X-ray absorption spectroscopy at the Ga K-edge. These data were compared with Ga-doped synthetic compounds (poorly crystalline hydroxyapatite, amorphous calcium phosphate and brushite) and with strontium-treated bone tissue, obtained from the same culture model. It was found that Sr(2+) substitutes for Ca(2+) in the HAP crystal lattice. In contrast, the replacement by Ga(3+) yielded a much more disordered local environment of the probe atom in all investigated cell culture samples. The coordination of Ga ions in the cell culture minerals was similar to that of Ga(3+), substituted for Ca(2+), in the Ga-doped synthetic brushite (Ga-DCPD). The Ga atoms in the Ga-DCPD were coordinated by four oxygen atoms (1.90 A) of the four phosphate groups and two oxygen atoms at 2.02 A. Interestingly, the local environment of Ga in the cell culture minerals was not dependent on the onset of Ga treatment, the Ga concentration in the medium or the age of the mineral. Thus, it was concluded that Ga ions were incorporated into the precursor phase to the HAP mineral. Substitution for Ca(2+ )with Ga(3+) distorted locally this brushite-like environment, which prevented the transformation of the initially deposited phase into the poorly crystalline HAP. PMID:14648284

  18. 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.

  19. 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

  20. 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

  1. Bone tissue engineering in osteoporosis.

    PubMed

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

    2013-06-01

    Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age. PMID:23562167

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  3. Vascularization in bone tissue engineering constructs

    PubMed Central

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

    2016-01-01

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

  4. The materials used in bone tissue engineering

    SciTech Connect

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

    2015-11-17

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

  5. 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.

  6. Vascularization in bone tissue engineering constructs.

    PubMed

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

    2015-03-01

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

  7. Brown adipose tissue and bone

    PubMed Central

    Lidell, M E; Enerbäck, S

    2015-01-01

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

  8. The influence of feed phosphates on the structural, mechanical and chemical properties of bone tissue in pigs.

    PubMed

    Nikodem, A; Dragan, Sz; Kołacz, Sz; Dobrzanski, Z

    2012-01-01

    The aim of the study was to assess the influence of various feed phosphates on the structural and mechanical properties as well as on the chemical composition of femurs in adult pigs (weight approx. 110 kg). Three types of phosphates--monocalcium phosphate (MCP), dicalcium phosphate (n-DCP) and calcium-sodium phosphate (CSP)--were used alternatively in pigs fed with the standard feed mixture. The MCP and CSP phosphates were typical, imported products used traditionally in pig feeding. Dicalcium phosphate (n-DCP) was manufactured in Poland on the basis of phosphoric acid with the new pro-ecological method. The following parameters were determined: the mean physical density of the samples of the compact and spongy bone tissue, values of Young's modulus, strength and the energy of deformation, and Vickers microhardness (HV). Also the content of C, O, Na, Mg, Al, and Si, as well as Ca, P and Sr was determined. Significant differences in mean values of the mentioned parameters occurred between the studied groups. The best mechanical properties were shown by the bones from the n-DCP group, and the compact bone tissue (diaphysis) contained the most Ca, P, and Sr when compared to the MCP and CSP groups. PMID:22844705

  9. Bone and Soft Tissue Ablation

    PubMed Central

    Foster, Ryan C.B.; Stavas, Joseph M.

    2014-01-01

    Bone and soft tissue tumor ablation has reached widespread acceptance in the locoregional treatment of various benign and malignant musculoskeletal (MSK) lesions. Many principles of ablation learned elsewhere in the body are easily adapted to the MSK system, particularly the various technical aspects of probe/antenna design, tumoricidal effects, selection of image guidance, and methods to reduce complications. Despite the common use of thermal and chemical ablation procedures in bone and soft tissues, there are few large clinical series that show longitudinal benefit and cost-effectiveness compared with conventional methods, namely, surgery, external beam radiation, and chemotherapy. Percutaneous radiofrequency ablation of osteoid osteomas has been evaluated the most and is considered a first-line treatment choice for many lesions. Palliation of painful metastatic bone disease with thermal ablation is considered safe and has been shown to reduce pain and analgesic use while improving quality of life for cancer patients. Procedure-related complications are rare and are typically easily managed. Similar to all interventional procedures, bone and soft tissue lesions require an integrated approach to disease management to determine the optimum type of and timing for ablation techniques within the context of the patient care plan. PMID:25053865

  10. Bone and soft tissue ablation.

    PubMed

    Foster, Ryan C B; Stavas, Joseph M

    2014-06-01

    Bone and soft tissue tumor ablation has reached widespread acceptance in the locoregional treatment of various benign and malignant musculoskeletal (MSK) lesions. Many principles of ablation learned elsewhere in the body are easily adapted to the MSK system, particularly the various technical aspects of probe/antenna design, tumoricidal effects, selection of image guidance, and methods to reduce complications. Despite the common use of thermal and chemical ablation procedures in bone and soft tissues, there are few large clinical series that show longitudinal benefit and cost-effectiveness compared with conventional methods, namely, surgery, external beam radiation, and chemotherapy. Percutaneous radiofrequency ablation of osteoid osteomas has been evaluated the most and is considered a first-line treatment choice for many lesions. Palliation of painful metastatic bone disease with thermal ablation is considered safe and has been shown to reduce pain and analgesic use while improving quality of life for cancer patients. Procedure-related complications are rare and are typically easily managed. Similar to all interventional procedures, bone and soft tissue lesions require an integrated approach to disease management to determine the optimum type of and timing for ablation techniques within the context of the patient care plan. PMID:25053865

  11. 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

  12. Structure and properties of nano-hydroxypatite scaffolds for bone tissue engineering with a selective laser sintering system.

    PubMed

    Shuai, Cijun; Gao, Chengde; Nie, Yi; Hu, Huanlong; Zhou, Ying; Peng, Shuping

    2011-07-15

    In this study, nano-hydroxypatite (n-HAP) bone scaffolds are prepared by a homemade selective laser sintering (SLS) system based on rapid prototyping (RP) technology. The SLS system consists of a precise three-axis motion platform and a laser with its optical focusing device. The implementation of arbitrary complex movements based on the non-uniform rational B-Spline (NURBS) theory is realized in this system. The effects of the sintering processing parameters on the microstructure of n-HAP are tested with x-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The particles of n-HAP grow gradually and tend to become spherical-like from the initial needle-like shape, but still maintain a nanoscale structure at scanning speeds between 200 and 300 mm min(-1) when the laser power is 50 W, the light spot diameter 4 mm, and the layer thickness 0.3 mm. In addition, these changes do not result in decomposition of the n-HAP during the sintering process. The results suggest that the newly developed n-HAP scaffolds have the potential to serve as an excellent substrate in bone tissue engineering. PMID:21642759

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

    PubMed Central

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

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface. PMID:26904121

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

    PubMed

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

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface. PMID:26904121

  15. 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. PMID:22669285

  16. [THE LEVELS OF OSTEOCALCIN AND PYRIDINOLINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: THE RELATIONSHIP WITH STRUCTURAL AND FUNCTIONAL STATE OF BONE TISSUE AND COURSE OF THE DESEASE].

    PubMed

    Shevchuk, S V; Denyschych, L P

    2015-01-01

    The article presents data on levels of osteocalcin and pyridinoline in patients with systemic lupus erythematosus (SLE), their comparison with structural and functional state of bone tissue and course of the disease. Bone metabolism derangements were found in 65.8% of women with SLE. Herewith, the increase of pyridinoline content was observed in 43.9% of patients, the reduction of osteocalcinin 39% of individuals. The deterioration of bone metabolism was associated with the severity of the disease, especially high levels of C-reactive protein (CRP) and interleukin-6 (IL-6) (r = 0.3-0.32), cumulative dose of glucocorticoids (GC) and low body mass index (BMI). Among patients with signs of biosynthetic inhibition and increasing of destructive processes in bone tissue were more often met people with osteopenia and osteoporosis. osteoporosis. PMID:27491152

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

    PubMed

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

    2014-01-01

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

  18. 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

  19. Chitosan-based scaffolds for bone tissue engineering

    PubMed Central

    Levengood, Sheeny Lan; Zhang, Miqin

    2014-01-01

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

  20. Cell interactions in bone tissue engineering

    PubMed Central

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

    2010-01-01

    Abstract 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. PMID:20050963

  1. 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

  2. Nanofractal surface structure under laser sintering of titanium and nitinol for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Shishkovsky, I.; Morozov, Yu.; Smurov, I.

    2007-12-01

    Comparative microanalysis and histological studies of porous titanium and nitinol (NiTi) implants fabricated by selective laser sintering are carried out. Sintered Ti and NiTi nanoporous structures are developed with grain sizes ranging from dozens to several hundreds nanometer and their formation is discussed. Dependence of the surface morphology of the implant on laser processing parameters (laser power, scanning velocity and beam diameter) is observed by analyzing the fractal-type nanostructure and its self-organization from the nano- to the macro-passing through the microlevel. It is shown that functional characteristics of the synthesized medical implants depend on the pores size distribution and their relative location as well as on the nanostructural morphology of the sintered surface.

  3. Microhardness of human cancellous bone tissue in progressive hip osteoarthritis.

    PubMed

    Tomanik, Magdalena; Nikodem, Anna; Filipiak, Jarosław

    2016-12-01

    Bone tissue is a biological system in which the dynamic processes of, among others, bone formation or internal reconstruction will determine the spatial structure of the tissue and its mechanical properties. The appearance of a factor disturbing the balance between biological processes, e.g. a disease, will cause changes in the spatial structure of bones, thus affecting its mechanical properties. One of the bone diseases most common in an increasingly ageing population is osteoarthritis, also referred to as degenerative joint disease. It is estimated that in 2050 about 1300 million people will show symptoms of OA. The appearance of a pathological stimulus disturbs the balance of the processes of degradation and synthesis of articular cartilage, chondrocytes and the extracellular matrix, and the subchondral bone layer. As osteoarthritis progresses, study of the epiphysis reveals increasingly widespread changes of the articular surface and the internal structure of bone tissue. In this paper, the authors point out the differences in the mechanical properties of cancellous bone tissue forming the proximal epiphysis of the femoral bone during the progressive stages of OA. In order to determine microproperties of bone trabeculae, specimens from different stages of the disease (N=9) were subjected to microindentation testing, which made it possible to determine the material properties of bone tissue, such as microhardness HV and Young׳s modulus E. In addition, mechanical tests were supplemented with Raman spectroscopy, which determine the degree of bone mineralization, and measurements of structural properties based on analysis using microCT. The conducted tests were used to establish both quantitative and quantitative description of changes in the structural and mechanical properties connected with reorganization of trabeculae making up the bone in the various stages of osteoarthritis. The proposed description will supplement existing knowledge in the literature about

  4. 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. PMID:25953540

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

    PubMed

    Paiva, Katiucia Batista Silva; Granjeiro, José Mauro

    2014-11-01

    Bone-forming cells originate from distinct embryological layers, mesoderm (axial and appendicular bones) and ectoderm (precursor of neural crest cells, which mainly form facial bones). These cells will develop bones by two principal mechanisms: intramembranous and endochondral ossification. In both cases, condensation of multipotent mesenchymal cells occurs, at the site of the future bone, which differentiate into bone and cartilage-forming cells. During long bone development, an initial cartilaginous template is formed and replaced by bone in a coordinated and refined program involving chondrocyte proliferation and maturation, vascular invasion, recruitment of adult stem cells and intense remodeling of cartilage and bone matrix. Matrix metalloproteinases (MMPs) are the most important enzymes for cleaving structural components of the extracellular matrix (ECM), as well as other non-ECM molecules in the ECM space, pericellular perimeter and intracellularly. Thus, the bioactive molecules generated act on several biological events, such as development, tissue remodeling and homeostasis. Since the discovery of collagenase in bone cells, more than half of the MMP members have been detected in bone tissues under both physiological and pathological conditions. Pivotal functions of MMPs during development and bone regeneration have been revealed by knockout mouse models, such as chondrocyte proliferation and differentiation, osteoclast recruitment and function, bone modeling, coupling of bone resorption and formation (bone remodeling), osteoblast recruitment and survival, angiogenesis, osteocyte viability and function (biomechanical properties); as such alterations in MMP function may alter bone quality. In this review, we look at the principal properties of MMPs and their inhibitors (TIMPs and RECK), provide an up-date on their known functions in bone development and remodeling and discuss their potential application to Bone Bioengineering. PMID:25157440

  6. 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

  7. Tissue-engineered autologous grafts for facial bone reconstruction.

    PubMed

    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

    2016-06-15

    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, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán 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 nonseeded 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

  8. 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

  9. 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

  10. 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. PMID:21097274

  11. 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. PMID:22766712

  12. Dentin Matrix Proteins in Bone Tissue Engineering

    PubMed Central

    Ravindran, Sriram

    2016-01-01

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

  13. Current Trends in Bone Tissue Engineering

    PubMed Central

    Péault, Bruno; James, Aaron W.

    2014-01-01

    The development of tissue engineering and regeneration constitutes a new platform for translational medical research. Effective therapies for bone engineering typically employ the coordinated manipulation of cells, biologically active signaling molecules, and biomimetic, biodegradable scaffolds. Bone tissue engineering has become increasingly dependent on the merging of innovations from each of these fields, as they continue to evolve independently. This foreword will highlight some of the most recent advances in bone tissue engineering and regeneration, emphasizing the interconnected fields of stem cell biology, cell signaling biology, and biomaterial research. These include, for example, novel methods for mesenchymal stem cell purification, new methods of Wnt signaling pathway manipulation, and cutting edge computer assisted nanoscale design of bone scaffold materials. In the following special issue, we sought to incorporate these diverse areas of emphasis in order to reflect current trends in the field. PMID:24804256

  14. 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

  15. Bone tissue as a systemic endocrine regulator.

    PubMed

    Zofkova, I

    2015-01-01

    Bone is a target tissue for hormones, such as the sex steroids, parathormon, vitamin D, calcitonin, glucocorticoids, and thyroid hormones. In the last decade, other "non-classic" hormones that modulate the bone tissue have been identified. While incretins (GIP and GLP-1) inhibit bone remodeling, angiotensin acts to promote remodeling. Bone morphogenetic protein (BMP) has also been found to have anabolic effects on the skeleton by activating bone formation during embryonic development, as well as in the postnatal period of life. Bone has also been identified as an endocrine tissue that produces a number of hormones, that bind to and modulate extra-skeletal receptors. Osteocalcin occupies a central position in this context. It can increase insulin secretion, insulin sensitivity and regulate metabolism of fatty acids. Moreover, osteocalcin also influences phosphate metabolism via osteocyte-derived FGF23 (which targets the kidneys and parathyroid glands to control phosphate reabsorption and metabolism of vitamin D). Finally, osteocalcin stimulates testosterone synthesis in Leydig cells and thus may play some role in male fertility. Further studies are necessary to confirm clinically important roles for skeletal tissue in systemic regulations. PMID:25470522

  16. Evolving concepts in bone tissue engineering.

    PubMed

    Cowan, Catherine M; Soo, Chia; Ting, Kang; Wu, Benjamin

    2005-01-01

    The field of tissue engineering integrates the latest advances in molecular biology, biochemistry, engineering, material science, and medical transplantation. Researchers in the developing field of regenerative medicine have identified bone tissue engineering as an attractive translational target. Clinical problems requiring bone regeneration are diverse, and no single regeneration approach will likely resolve all defects. Recent advances in the field of tissue engineering have included the use of sophisticated biocompatible scaffolds, new postnatal multipotent cell populations, and the appropriate cellular stimulation. In particular, synthetic polymer scaffolds allow for fast and reproducible construction, while still retaining biocompatible characteristics. These criteria relate to the immediate goal of determining the ideal implant. The search is becoming a reality with widespread availability of biocompatible scaffolds; however, the desired parameters have not been clearly defined. Currently, most research focuses on the use of bone morphogenetic proteins (BMPs), specifically BMP-2 and BMP-7. These proteins induce osteogenic differentiation in vitro, as well as bone defect healing in vivo. Protein-scaffold interactions that enhance BMP binding are of the utmost importance, since prolonged BMP release creates the most osteogenic microenvironment. Transition into clinical studies has had only mild success and relies on large doses of BMPs for bone formation. Advances within the field of bone tissue engineering will likely overcome these challenges and lead to more clinically relevant therapies. PMID:15797456

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

    PubMed Central

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

    2010-01-01

    Introduction Porphyromonas gingivalis has been associated with subgingival biofilms in adult periodontitis. However, the molecular mechanisms of its contribution to chronic gingival inflammation and loss of periodontal structural integrity remain unclear. The objectives of this investigation were to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. Methods P. gingivalis FDC 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip® arrays to provide a molecular profile of the events that occur following infection of these tissues. Results After P. gingivalis infection, 5517 and 1900 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P ≤ 0.05) and up-regulated. Biological pathways significantly impacted by P. gingivalis infection in tissues and calvarial bone included cell adhesion (immune system) molecules, Toll-like receptors, B cell receptor signaling, TGF-β cytokine family receptor signaling, and MHC class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T cell stimulation, and down regulation of antiviral and T cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption. Conclusion This is the first in vivo evidence that localized P. gingivalis infection differentially induces transcription of a broad array of host genes that differed between inflamed soft tissues and calvarial bone. PMID:20331794

  18. 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

  19. 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. PMID:27236664

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

    PubMed

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

    2016-09-01

    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

  1. Pullulan microcarriers for bone tissue regeneration.

    PubMed

    Aydogdu, Hazal; Keskin, Dilek; Baran, Erkan Turker; Tezcaner, Aysen

    2016-06-01

    Microcarrier systems offer a convenient way to repair bone defects as injectable cell carriers that can be applied with small incisions owing to their small size and spherical shape. In this study, pullulan (PULL) microspheres were fabricated and characterized as cell carriers for bone tissue engineering applications. PULL was cross-linked by trisodium trimetaphosphate (STMP) to enhance the stability of the microspheres. Improved cytocompatibility was achieved by silk fibroin (SF) coating and biomimetic mineralization on the surface by incubating in simulated body fluid (SBF). X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescent microscopy analysis confirmed biomimetic mineralization and SF coating on microspheres. The degradation analysis revealed that PULL microspheres had a slow degradation rate with 8% degradation in two weeks period indicating that the microspheres would support the formation of new bone tissue. Furthermore, the mechanical tests showed that the microspheres had a high mechanical stability that was significantly enhanced with the biomimetic mineralization. In vitro cell culture studies with SaOs-2 cells showed that cell viability was higher on SF and SBF coated microspheres on 7th day compared to PULL ones under dynamic conditions. Alkaline phosphatase activity was higher for SF coated microspheres in comparison to uncoated microspheres when dynamic culture condition was applied. The results suggest that both organic and inorganic surface modifications can be applied on PULL microspheres to prepare a biocompatible microcarrier system with suitable properties for bone tissue engineering. PMID:27040238

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

    PubMed

    Pletyanova, I V

    2016-01-01

    The objective of the present work was the primary forensic medical/medical criminalistic study of exhumed human remains with the determination of the main group characteristics for the purpose of evaluation of the degree of preservation of the soft tissues and bone structures under the conditions of prolonged corpse deposition in the high-latitude cryolitic zone. The materials available for the study consisted of the exhumed remains of 13 corpses. The author describes the transformed features of the soft tissues and bone structures. The former look like a grave wax. It is shown that the peculiar morphological features of the preserved soft tissues and bone structures depend on the burial depth and the characteristic natural factors of the high-latitude cryolitic zone. The main conditions influencing the state of the objects for the forensic medical expertise are considered including prescription of corpse burying, ground properties, freeze/thaw cycles, the influence of sea water, and microbiological factors. PMID:27500480

  3. [Analysis of bone tissues by intravital imaging].

    PubMed

    Mizuno, Hiroki; Yamashita, Erika; Ishii, Masaru

    2016-05-01

    In recent years,"the fluorescent imaging techniques"has made rapid advances, it has become possible to observe the dynamics of living cells in individuals or tissues. It has been considered that it is extremely difficult to observe the living bone marrow directly because bone marrow is surrounded by a hard calcareous. But now, we established a method for observing the cells constituting the bone marrow of living mice in real time by the use of the intravital two-photon imaging system. In this article, we show the latest data and the reports about the hematopoietic stem cells and the leukemia cells by using the intravital imaging techniques, and also discuss its further application. PMID:27117619

  4. 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. PMID:26117771

  5. Novel electrospun nanotholits/PHB scaffolds for bone tissue regeneration.

    PubMed

    Xavier Filho, Lauro; Olyveira, Gabriel Molina; Basmaji, Pierre; Costa, Ligia Maria Manzine

    2013-07-01

    Nanotholits is an osteoinductor or be, stimulates the bone regeneration, enabling bigger migration of the cells for formation of the bone tissue regeneration mainly because nanotholits are rich in minerals considered essential to the bone mineralization process on a protein matrix (otolin) as hydroxiapatite. In order to improve its biodegrability and bioresorption in new platforms for tissue engineering, it was electrospun PHB/nanotholits from aqueous solutions of this polymer at concentrations of nanotholits 1% (w/v) and compared morphological and thermal properties with PHB/nanotholits casting films. Electrospun PHB/nanotholits mats presents more symmetric nanopore structure than casting films mats observed by SEM images mainly because the orientation of pores along the longitudinal direction of the electrospun fibers. Nanotholits influences in PHB electrospun/casting was analyzed using transmission infrared spectroscopy (FTIR). TGA showed similar thermal properties but DSC showed distinct thermal properties and crystallinity process of the developed bionanocomposite mainly because of different processing. PMID:23901495

  6. Muscle and bone, two interconnected tissues.

    PubMed

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

    2015-05-01

    As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone-muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise. PMID:25804855

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

    PubMed

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

    2015-10-01

    Inappropriate bone growth in soft tissue can occur after trauma to a limb and can cause a disruption to the healing process. This is known as Heterotopic Ossification (HO) in which regions in the tissue start to mineralize and form microscopic bone-like structures. These structures continue to calcify and develop into large, non-functional bony masses that cause pain, limit limb movement, and expose the tissue to reoccurring infections; in the case of open wounds this can lead to amputation as a result of a failed wound. Both Magnetic Resonance Imaging (MRI) and X-ray imaging have poor sensitivity and specificity for the detection of HO, thus delaying therapy and leading to poor patient outcomes. We present a low-power, fast (1 frame per second) optical Raman imaging system with a large field of view (1 cm(2)) that can differentiate bone tissue from soft tissue without spectroscopy, this in contrast to conventional Raman microscopy systems. This capability may allow for the development of instrumentation which permits bedside diagnosis of HO. PMID:26504639

  8. Preclinical imaging in bone tissue engineering.

    PubMed

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

    2014-12-01

    Since X-rays were discovered, in 1895, and since the first radiological image of a hand, bone tissue has been the subject of detailed medical imaging. However, advances in bone engineering, including the increased complexity of implant scaffolds, currently also underline the limits of X-ray imaging. Therefore, advanced follow-up imaging methods are pivotal to develop. The field of noninvasive, high-sensitivity, and high-resolution anatomical and functional imaging techniques (optical, ultrasound, positron emission tomography, single-photon emission computed tomography, magnetic resonance, etc.) offers a wide variety of tools that potentially could be considered as alternatives, or at least supportive, to the most commonly used X-ray computed tomography. Moreover, dedicated preclinical scanners have become available, with sensitivity and resolution even higher than clinical scanners, thus favoring a quick translation from preclinical to clinical applications. Furthermore, the armamentarium of bone-specific probes and contrast agents for each of this imaging modalities is constantly growing. This review focuses on such preclinical imaging tools, each with its respective strengths and weaknesses, used alone or in combination. Especially, multimodal imaging will dramatically contribute to improve the knowledge on bone healing regenerative processes. PMID:24720381

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

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

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

  10. Tissue engineering of bone: material and matrix considerations.

    PubMed

    Khan, Yusuf; Yaszemski, Michael J; Mikos, Antonios G; Laurencin, Cato T

    2008-02-01

    When the normal physiologic reaction to fracture does not occur, such as in fracture nonunions or large-scale traumatic bone injury, surgical intervention is warranted. Autografts and allografts represent current strategies for surgical intervention and subsequent bone repair, but each possesses limitations, such as donor-site morbidity with the use of autograft and the risk of disease transmission with the use of allograft. Synthetic bone-graft substitutes, developed in an effort to overcome the inherent limitations of autograft and allograft, represent an alternative strategy. These synthetic graft substitutes, or matrices, are formed from a variety of materials, including natural and synthetic polymers, ceramics, and composites, that are designed to mimic the three-dimensional characteristics of autograft tissue while maintaining viable cell populations. Matrices also act as delivery vehicles for factors, antibiotics, and chemotherapeutic agents, depending on the nature of the injury to be repaired. This intersection of matrices, cells, and therapeutic molecules has collectively been termed tissue engineering. Depending on the specific application of the matrix, certain materials may be more or less well suited to the final structure; these include polymers, ceramics, and composites of the two. Each category is represented by matrices that can form either solid preformed structures or injectable forms that harden in situ. This article discusses the myriad design considerations that are relevant to successful bone repair with tissue-engineered matrices and provides an overview of several manufacturing techniques that allow for the actualization of critical design parameters. PMID:18292355

  11. Candidates Cell Sources to Regenerate Alveolar Bone from Oral Tissue

    PubMed Central

    Nishimura, Masahiro; Takase, Kazuma; Suehiro, Fumio; Murata, Hiroshi

    2012-01-01

    Most of the cases of dental implant surgery, especially the bone defect extensively, are essential for alveolar ridge augmentation. As known as cell therapy exerts valuable effects on bone regeneration, numerous reports using various cells from body to regenerate bone have been published, including clinical reports. Mesenchymal cells that have osteogenic activity and have potential to be harvested from intra oral site might be a candidate cells to regenerate alveolar bone, even dentists have not been harvested the cells outside of mouth. This paper presents a summary of somatic cells in edentulous tissues which could subserve alveolar bone regeneration. The candidate tissues that might have differentiation potential as mesenchymal cells for bone regeneration are alveolar bone chip, bone marrow from alveolar bone, periosteal tissue, and gingival tissue. Understanding their phenotype consecutively will provide a rational approach for alveolar ridge augmentation. PMID:22505911

  12. [Grading of soft tissue and bone sarcomas].

    PubMed

    Petersen, I; Wardelmann, E

    2016-07-01

    Malignancy grading is an essential element in the classification of sarcomas. It correlates with the prognosis of the disease and the risk of metastasis. This article presents the grading schemes for soft tissue, bone and pediatric sarcomas. It summarizes the histological criteria of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system and the Pediatric Oncology Group as well as the grading of bone tumors by the College of American Pathologists (CAP). Furthermore, the potential relevance of gene expression signatures, the complexity index in sarcoma (CINSARC) and single genetic alterations (p53, MDM2, p16, SWI/SNF, EWSR1 fusions and PAX3/PAX7-FOXO1 fusions) for the prognosis of sarcomas are discussed. PMID:27384333

  13. Bone and Soft Tissue Pathology: Diagnostic and Prognostic Implications.

    PubMed

    Gibbs, Julie; Henderson-Jackson, Evita; Bui, Marilyn M

    2016-10-01

    Soft tissue and bone tumors are a heterogeneous group of tumors most often classified according to the type of tissue they most closely histologically resemble. Although sarcomas are rare, greater than 100 histologic subtypes of benign and malignant soft tissue and bone tumors are currently recognized. In this article, the authors review the current pathologic definitions, the classification and grading systems, supportive ancillary techniques, and the prognostic implications for some of the more common soft tissue and bone tumors. PMID:27542635

  14. 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

  15. Biocomposite nanofibres and osteoblasts for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Venugopal, J.; Vadgama, P.; Sampath Kumar, T. S.; Ramakrishna, S.

    2007-02-01

    Nanofibres and nanocomposites are highly promising recent additions to materials in relation to tissue engineering. Mimicking the architecture of an extracellular matrix is one of the major challenges for tissue engineering. An operationally simple electrospinning technique was used to fabricate polycaprolactone/nanohydroxyapatite/collagen (PCL/nHA/Col) biocomposite nanofibrous scaffolds to provide mechanical support and to direct the growth of human fetal osteoblasts (hFOB) for tissue engineering of bone. Biocomposite nanofibres constructed with PCL, nHA and collagen type I combinations gave fibre diameters around 189 ± 0.026 to 579 ± 272 nm and pore sizes 2-35 µm. Resulting nanofibrous scaffolds were highly porous (>80%) structures and provided a sufficient open pore structure for cell occupancy whilst allowing free transport of nutrients and metabolic waste products; moreover, vascular in-growth was facilitated. The pore organization was determined by the deposition process, including interconnections of the fibre network. The mineralization was significantly increased (55%) in PCL/nHA/Col biocomposite nanofibrous scaffolds after 10 days of culture and appeared as minerals synthesized by osteoblast cells. The unique nanoscale biocomposite system had inherent surface functionalization for hFOB adhesion, migration, proliferation and mineralization to form a bone tissue for the regeneration of bone defects.

  16. 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

  17. 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. PMID:24399874

  18. [Modern poro-elastic biomechanical model of bone tissue. I. Biomechanical function of fluids in bone].

    PubMed

    Rogala, Piotr; Uklejewski, Ryszard; Stryła, Wanda

    2002-01-01

    The modern biomechanical two-phase poroelastic model of bone tissue is presented. Bone tissue is treated in this model as a porous elastically deformed solid filled with a viscous newtonian fluid. Traditional one-phase biomechanical model of bone tissue, which is characterized by the Young modulus and the Poisson's coefficient, is still valid and it can be treated as an approximate model in comparison with the more realistic two-phase model of bone tissue. The biomechanical function of fluids in bone is considered. Bone biodynamics is presented in form of the scheme which illustrates the mechano-adaptive, the mechano-electric and the electrophysiologic properties of bone tissue. Essentials of the poroelastic model of bone tissue is the mechanical load induced flow of intraosseous fluid and the associated strain generated electric potentials SGPs. PMID:12238403

  19. 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. PMID:23726922

  20. 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. PMID:27086202

  1. Water-mediated structuring of bone apatite.

    PubMed

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

    2013-12-01

    It is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite. This disordered layer is reminiscent of those found around the crystalline core of calcified biominerals in various natural composite materials in vivo. This work provides an extended local model of bone biomineralization. PMID:24193662

  2. 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. PMID:26748447

  3. 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

  4. Vascularised endosteal bone tissue in armoured sauropod dinosaurs.

    PubMed

    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

  5. Sarcomas of Soft Tissue and Bone.

    PubMed

    Ferrari, Andrea; Dirksen, Uta; Bielack, Stefan

    2016-01-01

    The definition of soft tissue and bone sarcomas include a large group of several heterogeneous subtypes of mesenchymal origin that may occur at any age. Among the different sarcomas, rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma and osteosarcoma are aggressive high-grade malignancies that often arise in adolescents and young adults. Managing these malignancies in patients in this age bracket poses various clinical problems, also because different therapeutic approaches are sometimes adopted by pediatric and adult oncologists, even though they are dealing with the same condition. Cooperation between pediatric oncologists and adult medical oncologists is a key step in order to assure the best treatment to these patients, preferably through their inclusion into international clinical trials. PMID:27595362

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

    SciTech Connect

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

    2013-12-16

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

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

    PubMed

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

    2015-07-01

    Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration. PMID:25934278

  8. [Quantitative plutonium microdistribution in bone tissue of vertebra from occupationally exposed worker].

    PubMed

    Levkina, E V; Romanov, S A; Miller, S C; Krahenbuhl, M P; Belosokhov, M V

    2008-01-01

    The purpose of this work is the receiving of quantitative data on Pu microdistribution in different structural elements of human bone tissue for local dose assessment and dosimetric models validation. Thoracic vertebra sample was taken for the study from former Mayak worker with rather high Pu burden, including information on occupational and exposure history, medical information and data on Pu content in organs. Lexan film autodiagrams were obtained using method of neutron-induced autoradiography from bone tissue sections. Quantitative analysis of randomly selected vision fields on one of autoradiograms was performed: fission fragment tracks Pu in different bone tissue areas were calculated, surface of bone tissue areas were defined. Quantitative information on Pu microdistribution in human bone tissue was obtained for the first time. On the basis of obtained data quantitative relation of Pu decays in bone volume to decays on bone surface in cortical and trabecular fractions were defined as 2.0 and 0.4, correspondingly. Actual quantitative relation of decays in bone volume to decays on bone surface is significantly different from recommended by ICRP for cortical fraction. Biokinetic model parameters of extrapulmonary ICRP compartment might need to be adjusted after expansion of data set on quantitative Pu microdistribution in other bone types in human that will involve new cases with different exposure pattern of radionuclide. PMID:18689262

  9. 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

  10. Anisotropy of bovine cortical bone tissue damage properties.

    PubMed

    Szabó, M E; Thurner, P J

    2013-01-01

    Bone is a heterogeneous, anisotropic natural composite material. Several studies have measured human cortical bone elastic properties in different anatomical directions and found that the Young's modulus was highest in the longitudinal, followed by the tangential and then by the radial direction. This study compared the Young's modulus, the accumulated microdamage and local strains related to the failure process in these three anatomical directions. Cortical bone samples (≈360 μm×360 μm) were mechanically tested in three-point bending and concomitantly imaged to assess local strains using digital image correlation technique. The bone whitening effect was used to detect microdamage formation and propagation. No statistically significant difference was found between the Young's modulus of longitudinal (9.4±2.0 GPa) and tangential (9.9±1.8 GPa) bovine bone samples, as opposed to previous findings on human bone samples. The same similarity was found for the whitening values (5000±1900 pix/mm(2) for longitudinal, 5800±2600 pix/mm(2) for tangential) and failure strains (16.8±7.0% for longitudinal, 19.1±3.2% for tangential) as well. However, significantly lower values were observed in the radial samples for Young's modulus (5.92±0.77 GPa), whitening (none or minimal) and failure strain (10.8±3.8%). For strains at whitening onset, no statistically significant difference was seen for the longitudinal (5.1±1.6%) and radial groups (4.2±2.0%), however, the tangential values were significantly greater (7.0±2.4%). The data implies that bovine cortical bone tissue in long bones is designed to withstand higher loads in the longitudinal and tangential directions than in the radial one. A possible explanation of the anisotropy in the mechanical parameters derived here might be the structure of the tissues in the three directions tested. PMID:23063771

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

    PubMed

    Kemp, Anne

    2013-10-01

    The connective tissue that links the bones of the mandible in the Australian lungfish, Neoceratodus forsteri, has been described as an intermandibular cartilage, and as such has been considered important for phylogenetic analyses among lower vertebrates. However, light and electron microscopy of developing lungfish jaws demonstrates that the intermandibular tissue, like the connective tissue that links the bones of the upper jaw, contains fibroblasts and numerous bundles of collagen fibrils, extending from the trabeculae of the bones supporting the tooth plates. It differs significantly in structure and in staining reactions from the cartilage and the bone found in this species. In common with the cladistian Polypterus and with actinopterygians and some amphibians, lungfish have no intermandibular cartilage. The connective tissue linking the mandibular bones has no phylogenetic significance for systematic grouping of lungfish, as it is present in a range of different groups among lower vertebrates. PMID:23801584

  12. 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

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

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

    PubMed

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

    2004-08-01

    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. PMID:15468269

  15. MRI manifestations of soft-tissue haemangiomas and accompanying reactive bone changes

    PubMed Central

    Pourbagher, A; Pourbagher, M A; Karan, B; Ozkoc, G

    2011-01-01

    Objectives Soft tissue haemangiomas are common benign vascular lesions that can be accompanied by reactive changes in the adjacent bone structure. This study aimed to discuss the MRI features of soft-tissue haemangiomas with an emphasis on changes in bone. Methods The radiographic and MRI findings of 23 patients (9 males, 14 females; mean age 25 years; age range 2–46 years) with soft-tissue haemangiomas were analysed retrospectively. MR images were evaluated for location of the lesion, size, configuration, signal features, contrast patterns, proximity to adjacent bone and changes in the accompanying bone. Excisional biopsy was performed in 15 patients. Results Radiographs demonstrated phleboliths in 8 patients (34%) and reactive bone changes in 4 (19%). On MRI, T1 weighted images showed that most of the lesions were isointense or isohyperintense, as compared with muscle tissue; however, on T2 weighted images all lesions appeared as hyperintense. Following intravenous gadolinium-diethylene triamine pentaacetic acid (DTPA) administration, homogeneous enhancement was observed in 3 lesions and heterogeneous enhancement was seen in 19. No enhancement was observed in one patient. Bone atrophy adjacent to the lesion was observed in four patients. Conclusion MRI is the most valuable means of diagnosing deep soft-tissue haemangiomas. Bone changes can accompany deeply situated haemangiomas; in four of our patients, we found atrophy of the bone adjacent to the lesion. To our knowledge, this is the first report in the literature regarding atrophy of the bone adjacent to a lesion. PMID:21123304

  16. Raman tomography of tissue phantoms and bone tissue

    NASA Astrophysics Data System (ADS)

    Schulmerich, Matthew V.; Srinivasan, Subhadra; Kreider, Jaclynn; Cole, Jacqueline H.; Dooley, Kathryn A.; Goldstein, Steven A.; Pogue, Brian W.; Morris, Michael D.

    2008-02-01

    We report tomographic reconstruction of objects located several millimeters below the surface of highly scattering media. For this purpose we adapted proven software developed for fluorescence tomography with and without the use of spatial priors1. For this first demonstration we acquired Raman spectra using an existing ring/disk fiber optic probe with fifty collection fibers2. Several illumination ring diameters were employed to generate multiple angles of incidence. Tomographic reconstruction from Raman scatter was tested using a 9.5 mm diameter Teflon® sphere embedded in a gel of agarose and 1% Intralipid. Blind reconstruction of the sphere using the 732 cm -1 C-F stretch yielded an accurate shape but an inaccurate depth. Using the known shape and position of the object as spatial priors, a more accurate reconstruction was obtained. We also demonstrated a reconstruction of the tibial diaphysis of an intact canine hind limb using spatial priors generated from micro-computed tomography. In this first demonstration of Raman tomography in animal tissue, the P-O stretch of the bone mineral at 958 cm -1 was used for the reconstruction. An accurate shape and depth were recovered.

  17. 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. PMID:25052837

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

    PubMed

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

    2012-05-21

    Human soft tissue is an important factor that influences the assessment of human long bones using quantitative ultrasound techniques. To investigate such influence, a series of soft tissue-bone phantoms (a bone-mimicking plate coated with a layer of water, glycerol or silicon rubber) were ultrasonically investigated using a probe with multi-emitter and multi-receiver arrays in an axial transmission configuration. A singular value decomposition signal processing technique was applied to extract the frequency-dependent wavenumbers of several guided modes. The results indicate that the presence of a soft tissue-mimicking layer introduces additional guided modes predicted by a fluid waveguide model. The modes propagating in the bone-mimicking plate covered by the soft-tissue phantom are only slightly modified compared to their counterparts in the free bone-mimicking plate, and they are still predicted by an elastic transverse isotropic two-dimensional waveguide. Altogether these observations suggest that the soft tissue-bone phantoms can be modeled as two independent waveguides. Even in the presence of the overlying soft tissue-mimicking layer, the modes propagating in the bone-mimicking plate can still be extracted and identified. These results suggest that our approach can be applied for the purpose of the characterization of the material and structural properties of cortical bone. PMID:22538382

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

    PubMed

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

    2015-04-01

    The development of responsive biomaterials capable of demonstrating modulated function in response to dynamic physiological and mechanical changes in vivo remains an important challenge in bone tissue engineering. To achieve long-term repair and good clinical outcomes, biologically responsive approaches that focus on repair and reconstitution of tissue structure and function through drug release, receptor recognition, environmental responsiveness and tuned biodegradability are required. Traditional orthopedic materials lack biomimicry, and mismatches in tissue morphology, or chemical and mechanical properties ultimately accelerate device failure. Multiple stimuli have been proposed as principal contributors or mediators of cell activity and bone tissue formation, including physical (substrate topography, stiffness, shear stress and electrical forces) and biochemical factors (growth factors, genes or proteins). However, optimal solutions to bone regeneration remain elusive. This review will focus on biological and physicomechanical considerations currently being explored in bone tissue engineering. PMID:25236302

  20. 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

  1. The role of perfusion bioreactors in bone tissue engineering

    PubMed Central

    Gaspar, Diana Alves; Gomide, Viviane; Monteiro, Fernando Jorge

    2012-01-01

    Tissue engineering has emerged as a possible alternative to current treatments for bone injuries and defects. However, the common tissue engineering approach presents some obstacles to the development of functional tissues, such as insufficient nutrient and metabolite transport and non-homogenous cell distribution. Culture of bone cells in three-dimensional constructs in bioreactor systems is a solution for those problems as it improves mass transport in the culture system. For bone tissue engineering spinner flasks, rotating wall vessels and perfusion systems have been investigated, and based on these, variations that support cell seeding and mechanical stimulation have also been researched. This review aims at providing an overview of the concepts, advantages and future applications of bioreactor systems for bone tissue engineering with emphasis on the design of different perfusion systems and parameters that can be optimized. PMID:23507883

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

    PubMed

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

    2016-10-01

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

  3. Bone Marrow Adipose Tissue: A New Player in Cancer Metastasis to Bone

    PubMed Central

    Morris, Emma V.; Edwards, Claire M.

    2016-01-01

    The bone marrow is a favored site for a number of cancers, including the hematological malignancy multiple myeloma, and metastasis of breast and prostate cancer. This specialized microenvironment is highly supportive, not only for tumor growth and survival but also for the development of an associated destructive cancer-induced bone disease. The interactions between tumor cells, osteoclasts and osteoblasts are well documented. By contrast, despite occupying a significant proportion of the bone marrow, the importance of bone marrow adipose tissue is only just emerging. The ability of bone marrow adipocytes to regulate skeletal biology and hematopoiesis, combined with their metabolic activity, endocrine functions, and proximity to tumor cells means that they are ideally placed to impact both tumor growth and bone disease. This review discusses the recent advances in our understanding of how marrow adipose tissue contributes to bone metastasis and cancer-induced bone disease. PMID:27471491

  4. The control of bone induction in soft tissues.

    PubMed

    Gray, D H; Speak, K S

    1979-09-01

    The induction of bone at the boundary of parenchymal organs has been studied using acid demineralized rib implants in rabbits. The induction of bone is usually confined to that portion of an implant protruding from such an organ though both scant cartilage induction and the induction of bone within the territory of parenchymal organs were seen on a few occasions. Neonatal splenectomy does not influence the inductive properties of bone matrix in muscle or other soft tissues. The inclusion of composite autografts of liver and acid demineralized bone in muscle results in a reduction in the induction rate. It is postulated that the parenchymal organs exclude osteoprogenitor cells and possibly blood-bone bone-marrow-derived osteoinductor releasing cells by some mechanism that is diffusable, thus preventing the initial inductive event. Composite grafts of matrix and muscle produce bone in these tissue, demonstrating that once bone cell differentiation by induction is initiated bone tissue develops even in spleen, liver and kidney parenchyma. PMID:389518

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

    PubMed

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

    2015-01-01

    Bone is a complex and hierarchical tissue consisting of nano hydroxyapatite and collagen as major portion. Several attempts have been made to prepare the artificial bone so as to replace the autograft and allograft treatment. Tissue engineering is a promising approach to solve the several issues and is also useful in the construction of artificial bone with materials including polymer, ceramics, metals, cells and growth factors. Composites consisting of polymer-ceramics, best mimic the natural functions of bone. Alginate, an anionic polymer owing enormous biomedical applications, is gaining importance particularly in bone tissue engineering due to its biocompatibility and gel forming properties. Several composites such as alginate-polymer (PLGA, PEG and chitosan), alginate-protein (collagen and gelatin), alginate-ceramic, alginate-bioglass, alginate-biosilica, alginate-bone morphogenetic protein-2 and RGD peptides composite have been investigated till date. These alginate composites show enhanced biochemical significance in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, alkaline phosphatase increase, excellent mineralization and osteogenic differentiation. Hence, alginate based composite biomaterials will be promising for bone tissue regeneration. This review will provide a broad overview of alginate preparation and its applications towards bone tissue engineering. PMID:25020082

  6. Donation FAQs (Bone and Tissue Allografts)

    MedlinePlus

    ... donor family services. Most organ, tissue and eye banks that are members of MTF send tissue to ... according to exact surgical specifications. Small, local tissue banks could not provide this level of quality in ...

  7. 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

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

    PubMed

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

    2010-10-01

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

  9. 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

  10. 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. PMID:26805518

  11. Targeting the hypoxic response in bone tissue engineering: A balance between supply and consumption to improve bone regeneration.

    PubMed

    Stiers, Pieter-Jan; van Gastel, Nick; Carmeliet, Geert

    2016-09-01

    Bone tissue engineering is a promising therapeutic alternative for bone grafting of large skeletal defects. It generally comprises an ex vivo engineered combination of a carrier structure, stem/progenitor cells and growth factors. However, the success of these regenerative implants largely depends on how well implanted cells will adapt to the hostile and hypoxic host environment they encounter after implantation. In this review, we will discuss how hypoxia signalling may be used to improve bone regeneration in a tissue-engineered construct. First, hypoxia signalling induces angiogenesis which increases the survival of the implanted cells as well as stimulates bone formation. Second, hypoxia signalling has also angiogenesis-independent effects on mesenchymal cells in vitro, offering exciting new possibilities to improve tissue-engineered bone regeneration in vivo. In addition, studies in other fields have shown that benefits of modulating hypoxia signalling include enhanced cell survival, proliferation and differentiation, culminating in a more potent regenerative implant. Finally, the stimulation of endochondral bone formation as a physiological pathway to circumvent the harmful effects of hypoxia will be briefly touched upon. Thus, angiogenic dependent and independent processes may counteract the deleterious hypoxic effects and we will discuss several therapeutic strategies that may be combined to withstand the hypoxia upon implantation and improve bone regeneration. PMID:26768117

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

    PubMed Central

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

    2014-01-01

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

  13. Stem cell origin differently affects bone tissue engineering strategies

    PubMed Central

    Mattioli-Belmonte, Monica; Teti, Gabriella; Salvatore, Viviana; Focaroli, Stefano; Orciani, Monia; Dicarlo, Manuela; Fini, Milena; Orsini, Giovanna; Di Primio, Roberto; Falconi, Mirella

    2015-01-01

    Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The fruitful selection and combination of tissue engineered scaffold, progenitor cells, and physiologic signaling molecules allowed the surgeon to reconstruct the missing natural tissue. On the basis of these considerations, we analyzed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e., periodontal ligament, maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, taking into account their specific features, they could be intriguing cell sources in different stem cell-based bone/periodontal tissue regeneration approaches. PMID:26441682

  14. Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration.

    PubMed

    Tang, Daniel; Tare, Rahul S; Yang, Liang-Yo; Williams, David F; Ou, Keng-Liang; Oreffo, Richard O C

    2016-03-01

    The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself. PMID:26803405

  15. Management of soft tissue and bone sarcomas

    SciTech Connect

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

    1986-01-01

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

  16. Melatonin Effects on Hard Tissues: Bone and Tooth

    PubMed Central

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

    2013-01-01

    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. PMID:23665905

  17. 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.

  18. 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.

  19. Individualised, micro CT-based finite element modelling as a tool for biomechanical analysis related to tissue engineering of bone.

    PubMed

    Jaecques, S V N; Van Oosterwyck, H; Muraru, L; Van Cleynenbreugel, T; De Smet, E; Wevers, M; Naert, I; Vander Sloten, J

    2004-04-01

    Load-bearing tissues, like bone, can be replaced by engineered tissues or tissue constructs. For the success of this treatment, a profound understanding is needed of the mechanical properties of both the native bone tissue and the construct. Also, the interaction between mechanical loading and bone regeneration and adaptation should be well understood. This paper demonstrates that microfocus computer tomography (microCT) based finite element modelling (FEM) can have an important contribution to the field of functional bone engineering as a biomechanical analysis tool to quantify the stress and strain state in native bone tissue and in tissue constructs. Its value is illustrated by two cases: (1) in vivo microCT-based FEM for the analysis of peri-implant bone adaptation and (2) design of biomechanically optimised bone scaffolds. The first case involves a combined animal experimental and numerical study, in which the peri-implant bone adaptive response is monitored by means of in vivo microCT scanning. In the second case microCT-based finite element models were created of native trabecular bone and bone scaffolds and a mechanical analysis of both structures was performed. Procedures to optimise the mechanical properties of bone scaffolds, in relation to those of native trabecular bone are discussed. PMID:14697870

  20. Spatial variation in osteonal bone properties relative to tissue and animal age.

    PubMed

    Gourion-Arsiquaud, Samuel; Burket, Jayme C; Havill, Lorena M; DiCarlo, Edward; Doty, Stephen B; Mendelsohn, Richard; van der Meulen, Marjolein C H; Boskey, Adele L

    2009-07-01

    Little is known about osteonal bone mineral and matrix properties, although these properties are of major importance for the understanding of bone alterations related to age and bone diseases such as osteoporosis. During aging, bone undergoes modifications that compromise their structural integrity as shown clinically by the increase of fracture incidence with age. Based on Fourier transform infrared (FTIR) analysis from baboons between 0 and 32 yr of age, consistent systematic variations in bone properties as a function of tissue age are reported within osteons. The patterns observed were independent of animal age and positively correlated with bone tissue elastic behavior measured by nano-indentation. As long as tissue age is expressed as a percentage of the entire osteon radius, osteonal analyses can be used to characterize disease changes independent of the size of the osteon. These mineral and matrix analyses can be used to explain bone fragility. The mineral content (mineral-to-matrix ratio) was correlated with the animal age in both old (interstitial) and newly formed bone tissue, showing for the first time that age-related changes in BMC can be explain by an alteration in the mineralization process itself and not only by an imbalance in the remodeling process. PMID:19210217

  1. Development of three-dimensional tissue engineered bone-oral mucosal composite models.

    PubMed

    Almela, Thafar; Brook, Ian M; Moharamzadeh, Keyvan

    2016-04-01

    Tissue engineering of bone and oral mucosa have been extensively studied independently. The aim of this study was to develop and investigate a novel combination of bone and oral mucosa in a single 3D in vitro composite tissue mimicking the natural structure of alveolar bone with an overlying oral mucosa. Rat osteosarcoma (ROS) cells were seeded into a hydroxyapatite/tri-calcium phosphate scaffold and bone constructs were cultured in a spinner bioreactor for 3 months. An engineered oral mucosa was fabricated by air/liquid interface culture of immortalized OKF6/TERET-2 oral keratinocytes on collagen gel-embedded fibroblasts. EOM was incorporated into the engineered bone using a tissue adhesive and further cultured prior to qualitative and quantitative assessments. Presto Blue assay revealed that ROS cells remained vital throughout the experiment. The histological and scanning electron microscope examinations showed that the cells proliferated and densely populated the scaffold construct. Micro computed tomography (micro-CT) scanning revealed an increase in closed porosity and a decrease in open and total porosity at the end of the culture period. Histological examination of bone-oral mucosa model showed a relatively differentiated parakeratinized epithelium, evenly distributed fibroblasts in the connective tissue layer and widely spread ROS cells within the bone scaffold. The feasibility of fabricating a novel bone-oral mucosa model using cell lines is demonstrated. Generating human 'normal' cell-based models with further characterization is required to optimize the model for in vitro and in vivo applications. PMID:26883949

  2. 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.

  3. Tissue engineering strategies for promoting vascularized bone regeneration.

    PubMed

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

    2016-02-01

    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

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

    PubMed

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

    2006-01-01

    Bone is the only body tissue capable of regeneration, allowing the restitutio ad integrum following trauma. In the event of a fracture or bone graft, new bone is formed, which following the remodeling process is identical to the pre-existing. Bone is a dynamic tissue in constant formation and resorption. This balanced phenomena, known as the remodeling process, allows the renovation of 5-15% of the total bone mass per year under normal conditions. Bone remodeling consists of the resorption of a certain amount of bone by osteoclasts, likewise the formation of osteoid matrix by osteoblasts, and its subsequent mineralization. This phenomenon occurs in small areas of the cortical bone or the trabecular surface, called Basic Multicellular Units (BMU). Treatment in Traumatology, Orthopedics, Implantology, and Maxillofacial and Oral Surgery, is based on the biologic principals of bone regeneration, in which cells, extracellular matrix, and osteoinductive signals are involved. The aim of this paper is to provide an up date on current knowledge on the biochemical and physiological mechanisms of bone regeneration, paying particular attention to the role played by the cells and proteins of the bone matrix. PMID:16388294

  5. [Effect of pulsed CO2-laser irradiation on bone tissue].

    PubMed

    Kholodnov, S E

    1985-01-01

    Different dynamic effects on biological tissue caused by pulsed laser radiation are described. It is shown that the parameters of these effects which take place on the bone tissue affected by pulsed CO2-laser radiation are directly dependent on the parameters of these pulses and may be predicted for any concrete application. PMID:3931698

  6. 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

  7. Dimethyloxaloylglycine Improves Angiogenic Activity of Bone Marrow Stromal Cells in the Tissue-Engineered Bone

    PubMed Central

    Ding, Hao; Chen, Song; Song, Wen-Qi; Gao, You-Shui; Guan, Jun-Jie; Wang, Yang; Sun, Yuan; Zhang, Chang-Qing

    2014-01-01

    One of the big challenges in tissue engineering for treating large bone defects is to promote the angiogenesis of the tissue-engineered bone. Hypoxia inducible factor-1α (HIF-1α) plays an important role in angiogenesis-osteogenesis coupling during bone regeneration, and can activate a broad array of angiogenic factors. Dimethyloxaloylglycine (DMOG) can activate HIF-1α expression in cells at normal oxygen tension. In this study, we explored the effect of DMOG on the angiogenic activity of bone mesenchymal stem cells (BMSCs) in the tissue-engineered bone. The effect of different concentrations of DMOG on HIF-1a expression in BMSCs was detected with western blotting, and the mRNA expression and secretion of related angiogenic factors in DMOG-treated BMSCs were respectively analyzed using qRT-PCR and enzyme linked immunosorbent assay. The tissue-engineered bone constructed with β-tricalcium phosphate (β-TCP) and DMOG-treated BMSCs were implanted into the critical-sized calvarial defects to test the effectiveness of DMOG in improving the angiogenic activity of BMSCs in the tissue-engineered bone. The results showed DMOG significantly enhanced the mRNA expression and secretion of related angiogenic factors in BMSCs by activating the expression of HIF-1α. More newly formed blood vessels were observed in the group treated with β-TCP and DMOG-treated BMSCs than in other groups. And there were also more bone regeneration in the group treated with β-TCP and DMOG-treated BMSCs. Therefore, we believed DMOG could enhance the angiogenic activity of BMSCs by activating the expression of HIF-1α, thereby improve the angiogenesis of the tissue-engineered bone and its bone healing capacity. PMID:25013382

  8. 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

  9. 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.

  10. 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.

  11. Analysis of anisotropic viscoelastoplastic properties of cortical bone tissues.

    PubMed

    Abdel-Wahab, Adel A; Alam, Khurshid; Silberschmidt, Vadim V

    2011-07-01

    Bone fractures affect the health of many people and have a significant social and economic effect. Often, bones fracture due to impacts, sudden falls or trauma. In order to numerically model the fracture of a cortical bone tissue caused by an impact it is important to know parameters characterising its viscoelastoplastic behaviour. These parameters should be measured for various orientations in a bone tissue to assess bone's anisotropy linked to its microstructure. So, the first part of this study was focused on quantification of elastic-plastic behaviour of cortical bone using specimens cut along different directions with regard to the bone axis-longitudinal (axial) and transverse. Due to pronounced non-linearity of the elastic-plastic behaviour of the tissue, cyclic loading-unloading uniaxial tension tests were performed to obtain the magnitudes of elastic moduli not only from the initial loading part of the cycle but also from its unloading part. Additional tests were performed with different deformation rates to study the bone's strain-rate sensitivity. The second part of this study covered creep and relaxation properties of cortical bone for two directions and four different anatomical positions-anterior, posterior, medial and lateral-to study the variability of bone's properties. Since viscoelastoplasticity of cortical bone affects its damping properties due to energy dissipation, the Dynamic Mechanical Analysis (DMA) technique was used in the last part of our study to obtain magnitudes of storage and loss moduli for various frequencies. Based on analysis of elastic-plastic behaviour of the bovine cortical bone tissue, it was found that magnitudes of the longitudinal Young's modulus for four cortical positions were in the range of 15-24 GPa, while the transversal modulus was lower--between 10 and 15 GPa. Axial strength for various anatomical positions was also higher than transversal strength with significant differences in magnitudes for those positions

  12. Hierarchically biomimetic scaffold of a collagen-mesoporous bioactive glass nanofiber composite for bone tissue engineering.

    PubMed

    Hsu, Fu-Yin; Lu, Meng-Ru; Weng, Ru-Chun; Lin, Hsiu-Mei

    2015-04-01

    Mesoporous bioactive glass nanofibers (MBGNFs) were prepared by a sol-gel/electrospinning technique. Subsequently, a collagen-MBGNF (CM) composite scaffold that simultaneously possessed a macroporous structure and collagen nanofibers was fabricated by a gelation and freeze-drying process. Additionally, immersing the CM scaffold in a simulated body fluid resulted in the formation of bone-like apatite minerals on the surface. The CM scaffold provided a suitable environment for attachment to the cytoskeleton. Based on the measured alkaline phosphatase activity and protein expression levels of osteocalcin and bone sialoprotein, the CM scaffold promoted the differentiation and mineralization of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the CM scaffold was examined using a rat calvarial defect model in vivo. The results revealed that CM is biodegradable and could promote bone regeneration. Therefore, a CM composite scaffold is a potential bone graft for bone tissue engineering applications. PMID:25805665

  13. Biomaterials mediated microRNA delivery for bone tissue engineering.

    PubMed

    Sriram, M; Sainitya, R; Kalyanaraman, V; Dhivya, S; Selvamurugan, N

    2015-03-01

    Bone tissue engineering is an alternative strategy to overcome the problems associated with traditional treatments for bone defects. A number of bioactive materials along with new techniques like porous scaffold implantation, gene delivery, 3D organ printing are now-a-days emerging for traditional bone grafts and metal implants. Studying the molecular mechanisms through which these biomaterials induce osteogenesis is an equally hot field. Biomaterials could determine the fate of a cell via microRNAs (miRNAs). miRNAs are short non-coding RNAs that act as post-transcriptional regulators of gene expression and play an essential role for regulation of cell specific lineages including osteogenesis. Thus, this review focuses the recent trends on establishing a link of biomaterials with miRNAs and their delivery for bone tissue engineering applications. PMID:25543062

  14. 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. PMID:26478356

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

    PubMed Central

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

    2008-01-01

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

  16. Nanoindentation on porous bioceramic scaffolds for bone tissue engineering.

    PubMed

    Chowdhury, S; Thomas, Vinoy; Dean, Derrick; Catledge, Shane A; Vohra, Yogesh K

    2005-11-01

    We report nanoindentation mechanical properties measurements on porous ceramic scaffolds made for tissue engineering applications. The scaffolds have been made from tricalcium phosphate (TCP), hydroxyapatite (HA) nanopowder and mixed powders of HA (50 wt%) and TCP (50 wt%) using the polyurethane sponge method, which produces open porous ceramic scaffolds through replication of a porous polymer template. The scaffolds prepared by this method have a controllable pore size and interconnected pore structure. The crystal structures and morphology of porous scaffolds were determined by X-ray diffraction (XRD) and atomic force microscopy (AFM) respectively. Nanoindentation measurements to a depth of 600 nm showed a Young's modulus value of 10.3 GPa for HA+TCP composite scaffolds and 1.5 GPa for TCP scaffolds. The hardness values were 240 MPa for HA+TCP composites and 21 MPa for TCP sample respectively. The results showed that the mechanical properties of the biodegradable scaffolds can be considerably enhanced with the addition of HA while maintaining the interconnected open pores and pore geometry desirable for bone tissue engineering. PMID:16433415

  17. 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

  18. Radiologic Approach to Bone and Soft Tissue Sarcomas.

    PubMed

    Caracciolo, Jamie T; Letson, G Douglas

    2016-10-01

    Diagnostic imaging plays an important role in evaluation and treatment planning of patients with musculoskeletal tumors. This article discusses various imaging modalities available in the work-up, staging, and surveillance of patients with primary bone and soft tissue neoplasms. A systematic approach to initial evaluation of newly suspected bone lesions and soft tissue masses is presented. Reviewed are relevant imaging features of musculoskeletal neoplasms that help predict tumor biology and risk of malignancy and findings that define internal tumor composition and allow for accurate preoperative histopathologic diagnosis before intervention. Finally, the role of diagnostic imaging in tumor staging, evaluation of response to neoadjuvant therapy, and postoperative surveillance is discussed. PMID:27542636

  19. 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

  20. 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. PMID:23932972

  1. 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

  2. Internal channel structures in trabecular bone

    NASA Astrophysics Data System (ADS)

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

    2004-10-01

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

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

    PubMed Central

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

    2013-01-01

    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. PMID:23653480

  4. Repercussions of NSAIDS drugs on bone tissue: the osteoblast.

    PubMed

    García-Martínez, O; De Luna-Bertos, E; Ramos-Torrecillas, J; Manzano-Moreno, F J; Ruiz, C

    2015-02-15

    Non-steroidal anti-inflammatory drugs (NSAIDs) can act by modulating the behavior of osteoblasts, including their proliferation, differentiation, adhesion, and migration, but not all NSAIDs have these effects. Our objective was to update the information on this issue in a review of the literature in order to offer guidance on the prescription of the appropriate NSAID(s) to patients requiring bone tissue repair. To review current knowledge of this issue by searching for all relevant publications since 2001 in the MEDLINE, EMBASE and Cochrane Library databases, we used the following descriptors: bone tissue, osteoblast, NSAIDs, Anti-inflammatory drugs. Published studies show that most NSAIDs have an adverse effect on osteoblast growth by cell cycle arrest and apoptosis induction. The effect on differentiation varies according to the drug, dose, and treatment time. Osteoblast adhesion is increased and migration decreased by some NSAIDs, such as indomethacin and diclofenac. The antigenic profile or phagocytic function can also be modulated by NSAIDs. In general, NSAIDs have an adverse effect on bone tissue and given the routine administration of NSAIDs to individuals requiring bone repair, in which the osteoblast has an essential role, this effect on bone should be borne in mind. PMID:25625244

  5. Positive Association Between Adipose Tissue and Bone Stiffness.

    PubMed

    Berg, R M; Wallaschofski, H; Nauck, M; Rettig, R; Markus, M R P; Laqua, R; Friedrich, N; Hannemann, A

    2015-07-01

    Obesity is often considered to have a protective effect against osteoporosis. On the other hand, several recent studies suggest that adipose tissue may have detrimental effects on bone quality. We therefore aimed to investigate the associations between body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) or abdominal subcutaneous adipose tissue (SAT), and bone stiffness. The study involved 2685 German adults aged 20-79 years, who participated in either the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) or the baseline examination of the SHIP-Trend cohort. VAT and abdominal SAT were quantified by magnetic resonance imaging. Bone stiffness was assessed by quantitative ultrasound (QUS) at the heel (Achilles InSight, GE Healthcare). The individual risk for osteoporotic fractures was determined based on the QUS-derived stiffness index and classified in low, medium, and high risk. Linear regression models, adjusted for sex, age, physical activity, smoking status, risky alcohol consumption, diabetes, and height (in models with VAT or abdominal SAT as exposure), revealed positive associations between BMI, WC, VAT or abdominal SAT, and the QUS variables broadband-ultrasound attenuation or stiffness index. Moreover, BMI was positively associated with speed of sound. Our study shows that all anthropometric measures including BMI and, WC as well as abdominal fat volume are positively associated with bone stiffness in the general population. As potential predictors of bone stiffness, VAT and abdominal SAT are not superior to easily available measures like BMI or WC. PMID:25929703

  6. Bio-inspired mineralization of hydroxyapatite in 3D silk fibroin hydrogel for bone tissue engineering.

    PubMed

    Jin, Yashi; Kundu, Banani; Cai, Yurong; Kundu, Subhas C; Yao, Juming

    2015-10-01

    To fabricate hard tissue implants with bone-like structure using a biomimetic mineralization method is drawing much more attentions in bone tissue engineering. The present work focuses in designing 3D silk fibroin hydrogel to modulate the nucleation and growth of hydroxyapatite crystals via a simple ion diffusion method. The study indicates that Ca(2+) incorporation within the hydrogel provides the nucleation sites for hydroxyapatite crystals and subsequently regulates their oriented growth. The mineralization process is regulated in a Ca(2+) concentration- and minerlization time-dependent way. Further, the compressive strength of the mineralized hydrogels is directly proportional with the mineral content in hydrogel. The orchestrated organic/inorganic composite supports well the viability and proliferation of human osteoblast cells; improved cyto-compatibility with increased mineral content. Together, the present investigation reports a simple and biomimetic process to fabricate 3D bone-like biomaterial with desired efficacy to repair bone defects. PMID:26209967

  7. The ABJS Nicolas Andry Award: Tissue engineering of bone and ligament: a 15-year perspective.

    PubMed

    Laurencin, Cato T; Khan, Yusuf; Kofron, Michele; El-Amin, Saadiq; Botchwey, Edward; Yu, Xiaojun; Cooper, James A

    2006-06-01

    Musculoskeletal repair is a major challenge for orthopaedic surgeons. The burden of repair is compounded by supply constraints and morbidity associated with autograft and allograft tissue. We report 15 years of research regarding tissue engineering and biological substitutes for bone and ligaments. Our approach has focused on biomaterial selection, scaffold development, cell selection, cell/material interaction, and growth factor delivery. We have extensively tested poly(ester), poly(anhydride), poly(phosphazene) derivatives, and composite materials using biocompatibility, degradation, and mechanical analyses for bone and ligament tissue engineering. We have developed novel three-dimensional matrices with a pore structure and mechanical properties similar to native tissue. We also have reported on the attachment, growth, proliferation, and differentiation of cells cultured on several scaffolds. Through extensive molecular analysis, in vitro culture condition analysis, and in vivo evaluation, our findings provide new methods of bone tissue regeneration using three-dimensional tissue engineered scaffolds, bioactive bone cement composite materials, and three-dimensional tissue engineered scaffolds for ligament regeneration. PMID:16741478

  8. 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.

  9. 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.

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2004-07-01

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

  12. 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

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

    PubMed

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

    2015-11-01

    Traditional tissue engineering procedures are expensive and time consuming. Facilitated endogenous tissue engineering (FETE) provides a solution that can avoid the ex vivo culture of autologous cells and initiate in situ reparative endogenous repair processes in vivo. This method involves fabricating a porous scaffold that mimics the environment present during the bone formation process, consisting of components that provide biomimetic interfacial interactions to cells. After the scaffold is implanted, progenitor cells provided by autologous bone marrow and surrounding tissues then differentiate to bone cells under the direction of the in situ scaffold. This paper reports a biomimetic method to prepare a hierarchically structured hybrid scaffold. Bone-like nano hydroxyapatite (HA) was crystallized from a collagen and chitosan (CC) matrix to form a porous scaffold. The in vivo study demonstrates that this nanohybrid scaffold supports excellent bone repair. This means that the FETE approach, in which the cell culture portion of traditional tissue engineering takes place in vivo, can promote the intrinsic regenerative potential of endogenous tissues. PMID:26320569

  14. Detection of nanoscale structural changes in bone using random lasers

    PubMed Central

    Song, Qinghai; Xu, Zhengbin; Choi, Seung Ho; Sun, Xuanhao; Xiao, Shumin; Akkus, Ozan; Kim, Young L.

    2010-01-01

    We demonstrate that the unique characteristics of random lasing in bone can be used to assess nanoscale structural alterations as a mechanical or structural biosensor, given that bone is a partially disordered biological nanostructure. In this proof-of-concept study, we conduct photoluminescence experiments on cortical bone specimens that are loaded in tension under mechanical testing. The ultra-high sensitivity, the large detection area, and the simple detection scheme of random lasers allow us to detect prefailure damage in bone at very small strains before any microscale damage occurs. Random laser-based biosensors could potentially open a new possibility for highly sensitive detection of nanoscale structural and mechanical alterations prior to overt microscale changes in hard tissue and biomaterials. PMID:21258558

  15. Biomechanical considerations of animal models used in tissue engineering of bone.

    PubMed

    Liebschner, Michael A K

    2004-04-01

    Tissue engineering combines the aspects of cell biology, engineering, material science, and surgery to generate new functional tissue, and provides an important approach to the repair of segmental defects and in restoring biomechanical function. The development of tissue-engineering strategies into clinical therapeutic protocols requires extensive, preclinical experimentation in appropriate animal models. The ultimate success of any treatment strategy must be established in these animal models before clinical application. It is clear that the demands of the biological and mechanical environment in the clinical repair of critical size defects with tissue-engineered materials is significantly different from those existing in experimental animals. The major considerations facing any tissue-engineering testing logic include the choice of the defect, the animal, the age of the animal, the anatomic site, the size of the lesion, and most importantly, the micro-mechanical environment. With respect to biomechanical considerations when selecting animals for tissue- engineering of bone, it is evident that no common criteria have been reported. While in smaller animals due to size constraint only structural properties of whole bones can be measured, in larger animals and humans both material properties and structural properties are of interest. Based on reported results, comparison between the tissue-engineered bone across species may be of importance in establishing better model selection criteria. It has already been found that the deformation of long bones is fairly constant across species, and that stress levels during gait are dependent on the weight of the animal and the material properties of the bone tissue. Future research should therefore be geared towards developing better biomechanical testing systems and then finding the right animal model for the existing equipment. PMID:14697871

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

    PubMed

    Özarslan, Ali Can; Yücel, Sevil

    2016-11-01

    Bioactive glass scaffolds that contain silica are high viable biomaterials as bone supporters for bone tissue engineering due to their bioactive behaviour in simulated body fluid (SBF). In the human body, these materials help inorganic bone structure formation due to a combination of the particular ratio of elements such as silicon (Si), calcium (Ca), sodium (Na) and phosphorus (P), and the doping of strontium (Sr) into the scaffold structure increases their bioactive behaviour. In this study, bioactive glass scaffolds were produced by using rice hull ash (RHA) silica and commercial silica based bioactive glasses. The structural properties of scaffolds such as pore size, porosity and also the bioactive behaviour were investigated. The results showed that undoped and Sr-doped RHA silica-based bioactive glass scaffolds have better bioactivity than that of commercial silica based bioactive glass scaffolds. Moreover, undoped and Sr-doped RHA silica-based bioactive glass scaffolds will be able to be used instead of undoped and Sr-doped commercial silica based bioactive glass scaffolds for bone regeneration applications. Scaffolds that are produced from undoped or Sr-doped RHA silica have high potential to form new bone for bone defects in tissue engineering. PMID:27524030

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

    PubMed Central

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

    2013-01-01

    Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology. PMID:23509421

  18. Xylan hemicellulose improves chitosan hydrogel for bone tissue regeneration

    PubMed Central

    Bush, Joshua R.; Liang, Haixiang; Dickinson, Molly; Botchwey, Edward A.

    2016-01-01

    The hemicellulose xylan, which has immunomodulatory effects, has been combined with chitosan to form a composite hydrogel to improve the healing of bone fractures. This thermally responsive and injectable hydrogel, which is liquid at room temperature and gels at physiological temperature, improves the response of animal host tissue compared with similar pure chitosan hydrogels in tissue engineering models. The composite hydrogel was placed in a subcutaneous model where the composite hydrogel is replaced by host tissue within 1 week, much earlier than chitosan hydrogels. A tibia fracture model in mice showed that the composite encourages major remodeling of the fracture callus in less than 4 weeks. A non-union fracture model in rat femurs was used to demonstrate that the composite hydrogel allows bone regeneration and healing of defects that with no treatment are unhealed after 6 weeks. These results suggest that the xylan/chitosan composite hydrogel is a suitable bone graft substitute able to aid in the repair of large bone defects.

  19. Ultrashort pulse laser interactions with cortical bone tissue for applications in orthopaedic surgery

    NASA Astrophysics Data System (ADS)

    Ashforth, Simon A.; Simpson, M. C.; Bodley, Owen; Oosterbeek, Reece

    2015-03-01

    Using a femtosecond pulsed laser system (pulse width = 100fs, repetition rate = 1kHz, λ = 800nm), ablation threshold studies of freshly culled bovine and ovine cortical bone samples were identified using the diameter regression technique. Using the D2 technique, the ablation threshold was found to lie within a range of 0.83 - 0.96 Jcm-2 and 0.89 - 0.95 Jcm-2 for ovine and bovine cortical bone respectively indicating that laser ablation of bone is irrespective of target species. The relationship between cortical bone tissue removal and the number of applied pulses was explored. By altering the laser spot translation rate, we varied the number of pulses at each point along scribed linear cuts. Optical Coherence Tomography (OCT) and PDMS casting indicates that cut depth is linearly dependent on the number of pulses applied to the tissue, irrespective of donor species. For single pulse ablation of ovine and bovine cortical bone, we determined that the ablation rates were 0.41 - 0.75 μm per pulse and 0.28 - 0.90 μm per pulse when pulses of fluences in the range 0.52 - 2.63 Jcm-2 were applied to ovine and bovine cortical bone tissue, respectively. Structural analysis of the ablation features using environmental scanning electron microscopy and optical microscopy were utilized to assess the ablation features and identify signs of damage to surrounding tissue. We observed no structural indications of thermal shockwave cracking, molten debris deposition or charring of the tissue whilst leaving hydroxyapatite crystal structure intact.

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

    PubMed Central

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

    2013-01-01

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

  1. 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. PMID:23165885

  2. Osteolipoma independent of bone tissue: a case report

    PubMed Central

    Alderete, Joseph F; Kose, Ozkan; Ozcan, Ayhan; Cicek, Ilker; Basbozkurt, Mustafa

    2009-01-01

    Introduction Lipomas are the most common benign soft tissue tumors and appear in any part of the body. They typically consist of mature adipose tissue. Osteolipoma is an extremely rare histologic variant of lipoma that contains mature lamellar bone within the tumor and osteolipoma independent of bone tissue are very rare. We report a case of histologically confirmed osteolipoma independent of bone located in the thigh. Case presentation A 47-year-old male presented with a progressively enlarging, painful mass which approximately 10 cm × 8 cm over the anteromedial aspect of his right thigh. Plain films, Computerized Tomography, Magnetic Resonance Imaging and ultrasound guided needle biopsy were performed. Given the benign imaging characteristics and fine needle aspiration, an excisional biopsy was undertaken. The definitive pathologic diagnosis was intramuscular osteolipoma without evidence of malignancy. No recurrence was observed after 18 months follow up. Conclusion Although ossifying lipomas are very rare, it is important to keep them in mind when a lesion with adipose tissue in combination with ossification is encountered. PMID:19918398

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

    PubMed Central

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

    2013-01-01

    The elastic properties of bone tissue determine the biomechanical behavior of bone at the organ level. It is now widely accepted that the nanoscale structure of bone plays an important role to determine the elastic properties at the tissue level. Hence, in addition to the mineral density, the structure and organization of the mineral nanoparticles and of the collagen microfibrils appear as potential key factors governing the elasticity. Many studies exist on the role of the organization of collagen microfibril and mineral nanocrystals in strongly remodeled bone. However, there is no direct experimental proof to support the theoretical calculations. Here, we provide such evidence through a novel approach combining several high resolution imaging techniques: scanning acoustic microscopy, quantitative scanning small-Angle X-ray scattering imaging and synchrotron radiation computed microtomography. We find that the periodic modulations of elasticity across osteonal bone are essentially determined by the orientation of the mineral nanoparticles and to a lesser extent only by the particle size and density. Based on the strong correlation between the orientation of the mineral nanoparticles and the collagen molecules, we conclude that the microfibril orientation is the main determinant of the observed undulations of microelastic properties in regions of constant mineralization in osteonal lamellar bone. This multimodal approach could be applied to a much broader range of fibrous biological materials for the purpose of biomimetic technologies. PMID:23472132

  4. Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regeneration.

    PubMed

    Serra, I R; Fradique, R; Vallejo, M C S; Correia, T R; Miguel, S P; Correia, I J

    2015-10-01

    Recently, bone tissue engineering emerged as a viable therapeutic alternative, comprising bone implants and new personalized scaffolds to be used in bone replacement and regeneration. In this study, biocompatible scaffolds were produced by freeze-drying, using different formulations (chitosan, chitosan/gelatin, chitosan/β-TCP and chitosan/gelatin/β-TCP) to be used as temporary templates during bone tissue regeneration. Sample characterization was performed through attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray diffraction and energy dispersive spectroscopy analysis. Mechanical characterization and porosity analysis were performed through uniaxial compression test and liquid displacement method, respectively. In vitro studies were also done to evaluate the biomineralization activity and the cytotoxic profile of the scaffolds. Scanning electron and confocal microscopy analysis were used to study cell adhesion and proliferation at the scaffold surface and within their structure. Moreover, the antibacterial activity of the scaffolds was also evaluated through the agar diffusion method. Overall, the results obtained revealed that the produced scaffolds are bioactive and biocompatible, allow cell internalization and show antimicrobial activity against Staphylococcus aureus. Such, make these 3D structures as potential candidates for being used on the bone tissue regeneration, since they promote cell adhesion and proliferation and also prevent biofilm development at their surfaces, which is usually the main cause of implant failure. PMID:26117793

  5. Cryogel-PCL combination scaffolds for bone tissue repair.

    PubMed

    Van Rie, Jonas; Declercq, Heidi; Van Hoorick, Jasper; Dierick, Manuel; Van Hoorebeke, Luc; Cornelissen, Ria; Thienpont, Hugo; Dubruel, Peter; Van Vlierberghe, Sandra

    2015-03-01

    The present work describes the development and the evaluation of cryogel-poly-ε-caprolactone combinatory scaffolds for bone tissue engineering. Gelatin was selected as cell-interactive biopolymer to enable the adhesion and the proliferation of mouse calvaria pre-osteoblasts while poly-ε-caprolactone was applied for its mechanical strength required for the envisaged application. In order to realize suitable osteoblast carriers, methacrylamide-functionalized gelatin was introduced into 3D printed poly-ε-caprolactone scaffolds created using the Bioplotter technology, followed by performing a cryogenic treatment which was concomitant with the redox-initiated, covalent crosslinking of the gelatin derivative (i.e. cryogelation). In a first part, the efficiency of the cryogelation process was determined using gel fraction experiments and by correlating the results with conventional hydrogel formation at room temperature. Next, the optimal cryogelation parameters were fed into the combinatory approach and the scaffolds developed were characterized for their structural and mechanical properties using scanning electron microscopy, micro-computed tomography and compression tests respectively. In a final part, in vitro biocompatibility assays indicated a good colonization of the pre-osteoblasts and the attachment of viable cells onto the cryogenic network. However, the results also show that the cellular infiltration throughout the entire scaffold is suboptimal, which implies that the scaffold design should be optimized by reducing the cryogel density. PMID:25690621

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

    SciTech Connect

    Mkhabela, Vuyiswa J.; Ray, Suprakas Sinha

    2015-05-22

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

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

    NASA Astrophysics Data System (ADS)

    Mkhabela, Vuyiswa J.; Ray, Suprakas Sinha

    2015-05-01

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

  8. Growth factor-eluting technologies for bone tissue engineering.

    PubMed

    Nyberg, Ethan; Holmes, Christina; Witham, Timothy; Grayson, Warren L

    2016-04-01

    Growth factors are essential orchestrators of the normal bone fracture healing response. For non-union defects, delivery of exogenous growth factors to the injured site significantly improves healing outcomes. However, current clinical methods for scaffold-based growth factor delivery are fairly rudimentary, and there is a need for greater spatial and temporal regulation to increase their in vivo efficacy. Various approaches used to provide spatiotemporal control of growth factor delivery from bone tissue engineering scaffolds include physical entrapment, chemical binding, surface modifications, biomineralization, micro- and nanoparticle encapsulation, and genetically engineered cells. Here, we provide a brief review of these technologies, describing the fundamental mechanisms used to regulate release kinetics. Examples of their use in pre-clinical studies are discussed, and their capacities to provide tunable, growth factor delivery are compared. These advanced scaffold systems have the potential to provide safer, more effective therapies for bone regeneration than the systems currently employed in the clinic. PMID:25967594

  9. Three-dimensional chitosan-nanohydroxyapatite composite scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Thein-Han, W. W.; Misra, R. D. K.

    2009-09-01

    We describe the structure of biodegradable chitosan-nanohydroxyapatite (nHA) composites scaffolds and their interaction with pre-osteoblasts for bone tissue engineering. The scaffolds were fabricated via freezing and lyophilization. The nanocomposite scaffolds were characterized by a highly porous structure and pore size of ˜50-125 μm, irrespective of nHA content. The observed significant enhancement in the biological response of pre-osteoblast on nanocomposite scaffolds expressed in terms of cell attachment, proliferation, and widespread morphology in relation to pure chitosan points toward their potential use as scaffold material for bone regeneration.

  10. An investigation into the feasibility of implementing fractal paradigms to simulate cancellous bone structure.

    PubMed

    Haire, T J; Ganney, P S; Langton, C M

    2001-01-01

    Cancellous bone consists of a framework of solid trabeculae interspersed with bone marrow. The structure of the bone tissue framework is highly convoluted and complex, being fractal and statistically self-similar over a limited range of magnifications. To date, the structure of natural cancellous bone tissue has been defined using 2D and 3D imaging, with no facility to modify and control the structure. The potential of four computer-generated paradigms has been reviewed based upon knowledge of other fractal structures and chaotic systems, namely Diffusion Limited Aggregation (DLA), Percolation and Epidemics, Cellular Automata, and a regular Grid with randomly relocated nodes. The resulting structures were compared for their ability to create realistic structures of cancellous bone rather than reflecting growth and form processes. Although the creation of realistic computer-generated cancellous bone structures is difficult, it should not be impossible. Future work considering the combination of fractal and chaotic paradigms is underway. PMID:11328644

  11. 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

  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. 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. PMID:27279797

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

    PubMed Central

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

    2016-01-01

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

  15. 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

  16. 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.

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

    PubMed

    Hernigou, Philippe

    2015-03-01

    During the 20th century, allograft implantation waned in popularity as a clinical activity. Reports appeared in the literature describing several small series of patients in whom bone was obtained from amputation specimens or recently deceased individuals. The concept of bone banking became a reality during and after World War II when the National Naval Tissue Bank was established in Bethesda and a number of small banks sprang up in hospitals throughout the world. Small fragments, either of cortical or medullary bone, from these banks were used heterotopically to augment spinal fusions, to implant into cyst cavities, or to serve as a scaffolding for repair of non- or delayed union of fractures of the long bones. PMID:25720358

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

    PubMed

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

    2016-09-01

    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

  19. 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

  20. A review of chitosan and its derivatives in bone tissue engineering.

    PubMed

    LogithKumar, R; KeshavNarayan, A; Dhivya, S; Chawla, A; Saravanan, S; Selvamurugan, N

    2016-10-20

    Critical-sized bone defects treated with biomaterials offer an efficient alternative to traditional methods involving surgical reconstruction, allografts, and metal implants. Chitosan, a natural biopolymer is widely studied for bone regeneration applications owing to its tunable chemical and biological properties. However, the potential of chitosan to repair bone defects is limited due to its water insolubility, faster in vivo depolymerization, hemo-incompatibility, and weak antimicrobial property. Functionalization of chitosan structure through various chemical modifications provides a solution to these limitations. In this review, current trends of using chitosan as a composite with other polymers and ceramics, and its modifications such as quaternization, carboxyalkylation, hydroxylation, phosphorylation, sulfation and copolymerization in bone tissue engineering are elaborated. PMID:27474556

  1. Adult stem cells in bone and cartilage tissue engineering.

    PubMed

    Salgado, António J; Oliveira, João T; Pedro, Adriano J; Reis, Rui L

    2006-09-01

    The progressive increase in life expectancy within the last century has led to the appearance of novel health related problems, some of those within the musculoskeletal field. Among the latter, one can find diseases such as osteoporosis, rheumatoid arthritis and bone cancer, just to mention some of the most relevant. Other related problems are those that arise from serious injuries, often leading to non-recoverable critical size defects. The therapies currently used to treat this type of diseases/injuries are based on the use of pharmaceutical agents, auto/allotransplant and synthetic materials. However, such solutions present a number of inconveniences and therefore, there is a constant search for novel therapeutic solutions. The appearance of a novel field of science called Tissue engineering brought some hope for the solution of the above mentioned problems. In this field, it is believed that by combining a 3D porous template--scaffold--with an adequate cell population, with osteo or chondrogenic potential, it will be possible to develop bone and cartilage tissue equivalents that when implanted in vivo, could lead to the total regeneration of the affected area. This ideal cell population should have a series of properties, namely a high osteo and chondrogenic potential and at the same time, should be easily expandable and maintained in cultures for long periods of time. Due to its natural and intrinsic properties, stem cells are one of the best available cell types. However, after this sentence, the readers may ask, "Which Stem Cells?". During the last 10/15 years, the scientific community witnessed and reported the appearance of several sources of stem cells with both osteo and chondrogenic potential. Therefore, the present review intends to make an overview of data reported on different sources of adult stem cells (bone marrow, periosteum, adipose tissue, skeletal muscle and umbilical cord) for bone and cartilage regenerative medicine, namely those focusing on

  2. Understanding the Structure of Bones

    MedlinePlus

    ... make up OI bone do not give the skeleton full strength because the quantity or shape of ... of fractures. They need more strength than the skeleton can provide. When growth stops after sexual maturation, ...

  3. ECM-Aware Cell-Graph Mining for Bone Tissue Modeling and Classification.

    PubMed

    Bilgin, Cemal Cagatay; Bullough, Peter; Plopper, George E; Yener, Bülent

    2009-10-21

    Pathological examination of a biopsy is the most reliable and widely used technique to diagnose bone cancer. However, it suffers from both inter- and intra- observer subjectivity. Techniques for automated tissue modeling and classification can reduce this subjectivity and increases the accuracy of bone cancer diagnosis. This paper presents a graph theoretical method, called extracellular matrix (ECM)-aware cell-graph mining, that combines the ECM formation with the distribution of cells in hematoxylin and eosin (H&E) stained histopathological images of bone tissues samples. This method can identify different types of cells that coexist in the same tissue as a result of its functional state. Thus, it models the structure-function relationships more precisely and classifies bone tissue samples accurately for cancer diagnosis. The tissue images are segmented, using the eigenvalues of the Hessian matrix, to compute spatial coordinates of cell nuclei as the nodes of corresponding cell-graph. Upon segmentation a color code is assigned to each node based on the composition of its surrounding ECM. An edge is hypothesized (and established) between a pair of nodes if the corresponding cell membranes are in physical contact and if they share the same color. Hence, multiple colored-cell-graphs coexist in a tissue each modeling a different cell-type organization. Both topological and spectral features of ECM-aware cell-graphs are computed to quantify the structural properties of tissue samples and classify their different functional states as healthy, fractured, or cancerous using support vector machines. Classification accuracy comparison to related work shows that ECM-aware cell-graph approach yields 90.0% whereas Delaunay triangulation and simple cell-graph approach achieves 75.0% and 81.1% accuracy, respectively. PMID:20543911

  4. [Effects of antiresorptive therapy on the structural and material properties of bone strength].

    PubMed

    Kishimoto, Hideaki

    2016-01-01

    Bone strength depends on its structural and material properties. Structural properties are determined by the size and shape of bone and also the microarchitecture. Material properties are determined by mineral crystallinity, collagen structure and microdamage in bone. The strength of bone is adapted to the needs of physical activities by biologic mechanisms, bone modeling and remodeling. The deterioration of bone strength in postmenopausal women is characterized by a trabecular bone deficit with poor trabecular connectivity and followed by a cortical bone deficit with trabeculation of endocortical bone and intracortical porosity due to accelerated bone remodeling. In high turnover osteoporosis antiresorptive therapy is effective in preventing the structural deficit and in increasing the stiffness and the toughness(bone strength)by increasing the mean degree of mineralization of bone tissue through the prolongation of secondary mineralization. But the long-term use of strong antiresorber, i.e. bisphosphonate or denosumab, would result in highly mineralized bone and disturbed repair of microcracks by inhibition of bone remodeling. Intermittent use or discontinuation of strong antiresorber after about 3-5 years of administration could be recommended to avoid the deterioration of bone strength. PMID:26728537

  5. 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. PMID:21447075

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

    PubMed Central

    Idowu, Bernadine; Cama, Giuseppe; Deb, Sanjukta

    2014-01-01

    Tissue engineering–based bone grafts are emerging as a viable alternative treatment modality to repair and regenerate tissues damaged as a result of disease or injury. The choice of the biomaterial component is a critical determinant of the success of the graft or scaffold; essentially, it must induce and allow native tissue integration, and most importantly mimic the hierarchical structure of the native bone. Calcium phosphate bioceramics are widely used in orthopaedics and dentistry applications due to their similarity to bone mineral and their ability to induce a favourable biological response. One such material is monetite, which is biocompatible, osteoconductive and has the ability to be resorbed under physiological conditions. The osteoinductive properties of monetite in vivo are known; however, little is known of the direct effect on osteoinduction of human mesenchymal stem cells in vitro. In this study, we evaluated the potential of monetite to induce and sustain human mesenchymal stem cells towards osteogenic differentiation. Human mesenchymal stem cells were seeded on the monetite scaffold in the absence of differentiating factors for up to 28 days. The gene expression profile of bone-specific markers in cells on monetite scaffold was compared to the control material hydroxyapatite. At day 14, we observed a marked increase in alkaline phosphatase, osteocalcin and osteonectin expressions. This study provides evidence of a suitable material that has potential properties to be used as a tissue engineering scaffold. PMID:24904727

  7. Conception on the Cell Mechanisms of Bone Tissue Loss

    NASA Astrophysics Data System (ADS)

    Rodionova, N. V.

    2008-06-01

    Basing on the analysis of available literature, the results of our own electron microscopic and radioautographic researches the data are presented about the morphofunctional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures after exposure of animals (rats, monkeys) to microgravity (station SLS-2, Bion-11). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered.

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

    SciTech Connect

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

    2009-12-15

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

  9. Use of microfocus computerized tomography as a new technique for characterizing bone tissue around oral implants.

    PubMed

    Van Oossterwyck, H; Duyck, J; Vander Sloten, J; Van der Perre, G; Jansen, J; Wevers, M; Naert, I

    2000-01-01

    Qualitative and quantitative analysis of peri-implant tissues around retrieved oral implants is typically done by means of light microscopy on thin histological sections containing the metal surface and the undecalcified bone. It remains, however, a labor-intensive and thus time-consuming job. Moreover, it is a destructive technique that allows tissue quantification in only a limited number of two-dimensional sections. As an alternative, we evaluated the bone structure around screw-shaped titanium implants by means of microfocus computerized tomography (micro-CT) because it presents a number of advantages compared to conventional sectioning techniques: micro-CT is nondestructive, fast, and allows a fully three-dimensional characterization of the bone structure around the implant. Images can be reconstructed in an arbitrary plane, and three-dimensional reconstructions are also possible. Because of its high resolution, individual trabeculae can be visualized. The accuracy of micro-CT was qualitatively evaluated by comparing histological sections with the corresponding CT slices for the same specimen. The overall trabecular structure is very similar according to both techniques. Even very close to the interface, the titanium implant does not seem to produce significant artifacts. Furthermore, because the complete digital data on the trabecular bone structure around the implant is available, it is possible to create finite-element models of the bone-implant system that model the trabeculae in detail so that mechanical stress transfer at the interface can be studied at the level of individual trabeculae. Therefore, micro-CT seems to be very promising for the in vitro assessment of the three-dimensional bone structure around oral implants. Further research will be needed to evaluate its accuracy in a more quantitative way. PMID:11831302

  10. 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.

  11. In silico evolution of functional morphology: a test on bone tissue biomechanics

    PubMed Central

    de Margerie, Emmanuel; Tafforeau, Paul; Rakotomanana, Lalaonirina

    2006-01-01

    Evolutionary algorithms (EAs) use Darwinian principles—selection among random variation and heredity—to find solutions to complex problems. Mostly used in engineering, EAs gain growing interest in ecology and genetics. Here, we assess their usefulness in functional morphology, introducing finite element modelling (FEM) as a simulated mechanical environment for evaluating the ‘fitness’ of randomly varying structures. We used this method to identify biomechanical adaptations in bone tissue, a long-lasting problem in skeletal morphology. The algorithm started with a bone tissue model containing randomly distributed vascular spaces. The EA randomly mutated the distribution of vascular spaces, and selected the new structure if its mechanical resistance was increased. After some thousands of generations, organized phenotypes emerged, containing vascular canals and sinuses, mimicking real bone tissue organizations. This supported the hypothesis that natural bone microstructures can result from biomechanical adaptation. Despite its limited faithfulness to reality, we discuss the ability of the EA+FEM method to assess adaptation in a dynamic evolutionary framework, which is not possible in the real world because of the generation times of macro-organisms. We also point out the interesting potential of EAs to simulate not only adaptation, but also concurrent evolutionary phenomenons such as historical contingency. PMID:16971336

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

    PubMed

    Maciejewska, Karina; Drzazga, Zofia; Kaszuba, Michał

    2014-01-01

    Osteoporosis is one of the most common debilitating disease around the world and it is more and more established among young people. There are well known recommendations for nutrition of newborns and children concerning adequate calcium and vitamin D intake in order to maintain proper bone density. Nevertheless, important role in structure and function of a healthy bone tissue is played by an integration between all constituents including elements other than Ca, like trace elements, which control vital processes in bone tissue. It is important from scientific point of view as well as prevention of bone diseases, to monitor the mineralization process considering changes of the concentration of minerals during first stage of bone formation. This work presents studies of trace element (zinc, strontium, and iron) concentration in bones and teeth of Wistar rats at the age of 7, 14, and 28 days. Energy dispersive X-ray fluorescence (EDXRF) was used to examine mandibles, skulls, femurs, tibiae, and incisors. The quantitative analysis was performed using fundamental parameters method (FP). Zn and Sr concentrations were highest for the youngest individuals and decreased with age of rats, while Fe content was stable in bone matrix for most studied bones. Our results reveal the necessity of monitoring concentration of not only major, but also minor elements, because the trace elements play special role in the first period of bone development. PMID:24615876

  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. Fluid-fluid level: a nonspecific finding in tumors of bone and soft tissue.

    PubMed

    Tsai, J C; Dalinka, M K; Fallon, M D; Zlatkin, M B; Kressel, H Y

    1990-06-01

    Fluid-fluid levels have commonly been reported to occur in aneurysmal bone cysts but have also been seen in telangiectatic osteosarcoma, chondroblastoma, and giant cell tumor of bone. The authors reviewed their experience with nine bone and three soft-tissue tumors that showed fluid-fluid levels on computed tomographic or magnetic resonance images. The bone tumors included fibrous dysplasia, simple bone cyst, recurrent malignant fibrous histiocytoma of bone, two classical osteosarcomas, and four aneurysmal bone cysts. The soft-tissue tumors included soft-tissue hemangioma and two synovial sarcomas. Except for aneurysmal bone cysts, these types of tumors have not been reported to be associated with fluid-fluid levels. Radiologic-pathologic correlation was available in seven patients; in all seven, the fluid-fluid levels indicated prior hemorrhage. The authors conclude that the presence of fluid-fluid levels in bone or soft-tissue tumors cannot be considered diagnostic of any particular tumor. PMID:2160676

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

    SciTech Connect

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

    2006-10-15

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

  16. The influence of hydrostatic pressure on tissue engineered bone development.

    PubMed

    Neßler, K H L; Henstock, J R; El Haj, A J; Waters, S L; Whiteley, J P; Osborne, J M

    2016-04-01

    The hydrostatic pressure stimulation of an appropriately cell-seeded porous scaffold within a bioreactor is a promising method for engineering bone tissue external to the body. We propose a mathematical model, and employ a suite of candidate constitutive laws, to qualitatively describe the effect of applied hydrostatic pressure on the quantity of minerals deposited in such an experimental setup. By comparing data from numerical simulations with experimental observations under a number of stimulation protocols, we suggest that the response of bone cells to an applied pressure requires consideration of two components; (i) a component describing the cell memory of the applied stimulation, and (ii) a recovery component, capturing the time cells require to recover from high rates of mineralisation. PMID:26796221

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

    PubMed

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

    2010-12-01

    Native bone extracellular matrix (ECM) is a complex hierarchical fibrous composite structure, resulting from the assembling of collagen fibrils at several length scales, ranging from the macro to the nanoscale. The combination of nanofibers within microfibers after conventional reinforcement methodologies seems to be a feasible solution to the rational design of highly functional synthetic ECM substitutes. The present work aims at the development of bone ECM inspired structures, conjugating electrospun chitosan (Cht) nanofibers within biodegradable polymeric microfibers [poly(butylene succinate)-PBS and PBS/Cht], assembled in a fiber mesh structure. The nanofibers-reinforced composite fiber mesh scaffolds were seeded with human bone marrow mesenchymal stem cells (hBMSCs) and cultured under osteogenic differentiation conditions. These nanofibers-reinforced composite scaffolds sustained ECM deposition and mineralization, mainly in the PBS/Cht-based fiber meshes, as depicted by the increased amount of calcium phosphates produced by the osteogenic differentiated hBMSCs. The osteogenic genotype of the cultured hBMSCs was confirmed by the expression of osteoblastic genes, namely Alkaline Phosphatase, Osteopontin, Bone Sialoprotein and Osteocalcin, and the transcription factors Runx2 and Osterix, all involved in different stages of the osteogenesis. These data represent the first report on the biological functionality of nanofibers-reinforced composite scaffolds, envisaging the applicability of the developed structures for bone tissue engineering. PMID:20666612

  18. 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

  19. Bone structure as revealed by microtomography

    NASA Astrophysics Data System (ADS)

    Hildebrand, Tor; Laib, Andres; Ulrich, Dieter; Kohlbrenner, Adrian; Ruegsegger, Peter

    1997-10-01

    The appearance of cancellous bone architecture is different for various skeletal sites and various disease states. In the iliac crest it is more plate-like, whereas in the spine rods dominate. During aging and disease plates are perforated and connecting rods are dissolved. There is a continuous shift from one structural type to the other. So traditional histomorphometric procedures, which are based on a fixed model type, will lead to questionable results. 3D microtomography allows to assess model independent structural parameters so that trabecular thickness, for example, can be determined directly. Not only mean thicknesses are available but also thickness histograms which are helpful to identify pathological states. Other features such as trabecular separation, degree of anisotropy and structural type index can be extracted from the 3D images and allow to characterize cancellous bone and its changes due to aging, disease and treatment. To fully exploit the significance of bone structure on bone strength large scale finite element (FE) analyses are performed. Hence microtomography, performed with a sufficiently fine isotropic spatial resolution, reveals information on the structural features of cancellous bone which were not available so far and which will, hopefully, lead to a better understanding of the pathogenesis of bone diseases and subsequently to improved treatment regimes.

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

    PubMed

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

    2015-04-01

    The number of patients requiring flat bone transplantation continues to increase worldwide. Cell transplantation has been successfully applied clinically; however, it causes another defect site and the time requirements to harvest cells and expand them are considerable. In this study, KLD12/KLD12-SP (KLD12+KLD12-substance P [SP]) was designed to mimic endogenous tissue-healing processes. The structures of KLD12, KLD12-SP, and KLD12/KLD12-SP were observed by transmission electron microscopy and circular dichroism spectra. KLD12/KLD12-SP nanofibers (5-10 nm) were created under physiological conditions by formation of a β-sheet structure. The ability of mesenchymal stem cells (MSCs) to recruit KLD12/KLD12-SP was observed by using an in vivo fluorescence imaging system. Labeled human bone marrow stromal cells supplied via an intravenous injection were recruited to the scaffold containing KLD12/KLD12-SP. Polylactic acid/beta-tricalcium phosphate (PLA/β-TCP) scaffolds filled with KLD12/KLD12-SP were applied to repair calvarial defects. The composite constructs (groups: defect, PLA/β-TCP, PLA/β-TCP/KLD12, and PLA/β-TCP/KLD12/KLD12-SP) were implanted into rat defect sites. Bone tissue regeneration was evaluated by observing gross morphology by hematoxylin and eosin and Masson's trichrome staining at 12 and 24 weeks after surgery. Gross morphology showed that the defect site was filled with new tissue that was integrated with host tissue in the KLD12/KLD12-SP group. In addition, from the staining data, cells were recruited to the defect site and lacunae structures formed in the KLD12/KLD12-SP group. From these results, the PLA/β-TCP+KLD12/KLD12-SP composite construct was considered for enhancement of bone tissue regeneration without cell transplantation. PMID:25411965

  1. Structural features underlying raloxifene's biophysical interaction with bone matrix.

    PubMed

    Bivi, Nicoletta; Hu, Haitao; Chavali, Balagopalakrishna; Chalmers, Michael J; Reutter, Christopher T; Durst, Gregory L; Riley, Anna; Sato, Masahiko; Allen, Matthew R; Burr, David D; Dodge, Jeffrey A

    2016-02-15

    Raloxifene, a selective estrogen receptor modulator (SERM), reduces fracture risk at least in part by improving the mechanical properties of bone in a cell- and estrogen receptor-independent manner. In this study, we determined that raloxifene directly interacts with the bone tissue. Through the use of multiple and complementary biophysical techniques including nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR), we show that raloxifene interacts specifically with the organic component or the organic/mineral composite, and not with hydroxyapatite. Structure-activity studies reveal that the basic side chain of raloxifene is an instrumental determinant in the interaction with bone. Thus, truncation of portions of the side chain reduces bone binding and also diminishes the increase in mechanical properties. Our results support a model wherein the piperidine interacts with bone matrix through electrostatic interactions with the piperidine nitrogen and through hydrophobic interactions (van der Waals) with the aliphatic groups in the side chain and the benzothiophene core. Furthermore, in silico prediction of the potential binding sites on the surface of collagen revealed the presence of a groove with sufficient space to accommodate raloxifene analogs. The hydroxyl groups on the benzothiophene nucleus, which are necessary for binding of SERMs to the estrogen receptor, are not required for binding to the bone surface, but mediate a more robust binding of the compound to the bone powder. In conclusion, we report herein a novel property of raloxifene analogs that allows them to interact with the bone tissue through potential contacts with the organic matrix and in particular collagen. PMID:26795112

  2. 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. PMID:25802865

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

    NASA Astrophysics Data System (ADS)

    Kaiplavil, Sreekumar; Mandelis, Andreas

    2012-02-01

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

  4. The state of human bone tissue during space flight

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed Central

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

    2012-01-01

    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. PMID:22279159

  6. 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.

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

    PubMed

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

    2000-02-24

    N-Glycan structures of osteopontin (a bone matrix protein) from human bone (lumbar vertabrate) are reported in detail. Asn-linked glycan portion was released from 100 microg of osteopontin by digestion with glycoamidase A (from sweet almond), and the reducing ends of the N-glycans were reductively aminated with 2-aminopyridine. The derivatized N-glycans were separated and structurally identified by a multidimensional mapping technique on HPLC columns. Two major N-glycan structures were also confirmed by mass spectrometry. The proposed structures are shown below. The result should permit future comparison with the N-glycan structures of osteopontins obtained from other sources (kidney tissues, macrophages, urinary stones, human milk, etc.). PMID:10679288

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

    PubMed

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

    2015-06-01

    β-Ketonitrile tautomeric copolymers have demonstrated tunable hydrophilicity/hydrophobicity properties according to surrounding environment, and mechanical properties similar to those of human bone tissue. Both characteristic properties make them promising candidates as biomaterials for bone tissue engineering. Based on this knowledge we have designed two scaffolds based on β-ketonitrile tautomeric copolymers which differ in chemical composition and surface morphology. Two of them were nanostructured, using an anodized aluminum oxide (AAO) template, and the other two obtained by solvent casting methodology. They were used to evaluate the effect of the composition and their structural modifications on the biocompatibility, cytotoxicity and degradation properties. Our results showed that the nanostructured scaffolds exhibited higher degradation rate by macrophages than casted scaffolds (6 and 2.5% of degradation for nanostructured and casted scaffolds, respectively), a degradation rate compatible with bone regeneration times. We also demonstrated that the β-ketonitrile tautomeric based scaffolds supported osteoblastic cell proliferation and differentiation without cytotoxic effects, suggesting that these biomaterials could be useful in the bone tissue engineering field. PMID:25842133

  9. Bone marrow adipose tissue: formation, function and regulation.

    PubMed

    Suchacki, Karla J; Cawthorn, William P; Rosen, Clifford J

    2016-06-01

    The human body requires an uninterrupted supply of energy to maintain metabolic homeostasis and energy balance. To sustain energy balance, excess consumed calories are stored as glycogen, triglycerides and protein, allowing the body to continue to function in states of starvation and increased energy expenditure. Adipose tissue provides the largest natural store of excess calories as triglycerides and plays an important role as an endocrine organ in energy homeostasis and beyond. This short review is intended to detail the current knowledge of the formation and role of bone marrow adipose tissue (MAT), a largely ignored adipose depot, focussing on the role of MAT as an endocrine organ and highlighting the pharmacological agents that regulate MAT. PMID:27022859

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

    PubMed

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

    2015-09-01

    After internal contamination, uranium rapidly distributes in the body; up to 20 % of the initial dose is retained in the skeleton, where it remains for years. Several studies suggest that uranium has a deleterious effect on the bone cell system, but little is known regarding the mechanisms leading to accumulation of uranium in bone tissue. We have performed synchrotron radiation-based micro-X-ray fluorescence (SR μ-XRF) studies to assess the initial distribution of uranium within cortical and trabecular bones in contaminated rats' femurs at the micrometer scale. This sensitive technique with high spatial resolution is the only method available that can be successfully applied, given the small amount of uranium in bone tissue. Uranium was found preferentially located in calcifying zones in exposed rats and rapidly accumulates in the endosteal and periosteal area of femoral metaphyses, in calcifying cartilage and in recently formed bone tissue along trabecular bone. Furthermore, specific localized areas with high accumulation of uranium were observed in regions identified as micro-vessels and on bone trabeculae. These observations are of high importance in the study of the accumulation of uranium in bone tissue, as the generally proposed passive chemical sorption on the surface of the inorganic part (apatite) of bone tissue cannot account for these results. Our study opens original perspectives in the field of exogenous metal bio-mineralization. PMID:26084548

  11. 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.

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

    PubMed Central

    Venkatesan, Jayachandran; Bhatnagar, Ira; Kim, Se-Kwon

    2014-01-01

    Over the last few years, significant research has been conducted in the construction of artificial bone scaffolds. In the present study, different types of polymer scaffolds, such as chitosan-alginate (Chi-Alg) and chitosan-alginate with fucoidan (Chi-Alg-fucoidan), were developed by a freeze-drying method, and each was characterized as a bone graft substitute. The porosity, water uptake and retention ability of the prepared scaffolds showed similar efficacy. The pore size of the Chi-Alg and Chi-Alg-fucoidan scaffolds were measured from scanning electron microscopy and found to be 62–490 and 56–437 µm, respectively. In vitro studies using the MG-63 cell line revealed profound cytocompatibility, increased cell proliferation and enhanced alkaline phosphatase secretion in the Chi-Alg-fucoidan scaffold compared to the Chi-Alg scaffold. Further, protein adsorption and mineralization were about two times greater in the Chi-Alg-fucoidan scaffold than the Chi-Alg scaffold. Hence, we suggest that Chi-Alg-fucoidan will be a promising biomaterial for bone tissue regeneration. PMID:24441614

  13. 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

  14. 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. PMID:26179958

  15. 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

  16. Freeze-cast hydroxyapatite scaffolds for bone tissue engineering applications.

    PubMed

    Fu, Qiang; Rahaman, Mohamed N; Dogan, Fatih; Bal, B Sonny

    2008-06-01

    Freeze casting of aqueous suspensions was investigated as a method for preparing porous hydroxyapatite (HA) scaffolds for eventual application to bone tissue engineering. Suspensions of HA particles (10-20 volume percent) were frozen unidirectionally in a cylindrical mold placed on a cold steel substrate (-20 degrees C). After sublimation of the ice, sintering for 3 h at 1350 degrees C produced constructs with dense HA lamellae, with porosity of approximately 50%, and inter-lamellar pore widths of 5-30 microm. These constructs had compressive strengths of 12 +/- 1 MPa and 5 +/- 1 MPa in the directions parallel and perpendicular to the freezing direction, respectively. Manipulation of the microstructure was achieved by modifying the solvent composition of the suspension used for freeze casting. The use of water-glycerol mixtures (20 wt% glycerol) resulted in the production of constructs with finer pores (1-10 microm) and a larger number of dendritic growth connecting the HA lamellae, and higher strength. On the other hand, the use of water-dioxane mixtures (60 wt% dioxane) resulted in a cellular-type microstructure with larger pores (90-110 microm). The mechanical response showed high strain tolerance (5-10% at the maximum stress), high strain for failure (>20%) and sensitivity to the loading rate. The favorable mechanical behavior of the porous constructs, coupled with the ability to modify their microstructure, indicates the potential of the present freeze casting route for the production of porous scaffolds for bone tissue engineering. PMID:18458369

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

    PubMed

    Kumar, Alok; Biswas, Krishanu; Basu, Bikramjit

    2015-02-01

    The research work on bulk hydroxyapatite (HA)-based composites are driven by the need to develop biomaterials with better mechanical properties without compromising its bioactivity and biocompatibility properties. Despite several years of research, the mechanical properties of the HA-based composites still need to be enhanced to match the properties of natural cortical bone. In this regard, the scope of this review on the HA-based bulk biomaterials is limited to the processing and the mechanical as well as biocompatibility properties for bone tissue engineering applications of a model system that is hydroxyapatite-titanium (HA-Ti) bulk composites. It will be discussed in this review how HA-Ti based bulk composites can be processed to have better fracture toughness and strength without compromising biocompatibility. The advantages of the functionally gradient materials to integrate the mechanical and biocompatibility properties is a promising approach in hard tissue engineering and has been emphasized here in reference to the limited literature reports. On the biomaterials fabrication aspect, the recent results are discussed to demonstrate that advanced manufacturing techniques, like spark plasma sintering can be adopted as a processing route to restrict the sintering reactions, while enhancing the mechanical properties. Various toughening mechanisms related to careful tailoring of microstructure are discussed. The in vitro cytocompatibilty, cell fate processes as well as in vivo biocompatibility results are also reviewed and the use of flow cytometry to quantify in vitro cell fate processes is being emphasized. PMID:24737723

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

    PubMed

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

    2015-07-01

    Biomaterial scaffolds meant to function as supporting structures to osteogenic cells play a pivotal role in bone tissue engineering. Recently, we synthesized an aliphatic polyurethane (PU) scaffold via a foaming method using non-toxic components. Through this procedure a uniform interconnected porous structure was created. Furthermore, hydroxyapatite (HA) particles were introduced into this process to increase the bioactivity of the PU matrix. To evaluate the biological performances of these PU-based scaffolds, their influence on in vitro cellular behavior and in vivo bone forming capacity of the engineered cell-scaffold constructs was investigated in this study. A simulated body fluid test demonstrated that the incorporation of 40 wt % HA particles significantly promoted the biomineralization ability of the PU scaffolds. Enhanced in vitro proliferation and osteogenic differentiation of the seeded mesenchymal stem cells were also observed on the PU/HA composite. Next, the cell-scaffold constructs were implanted subcutaneously in a nude mice model. After 8 weeks, a considerable amount of vascularized bone tissue with initial marrow stroma development was generated in both PU and PU/HA40 scaffold. In conclusion, the PU/HA composite is a potential scaffold for bone regeneration applications. PMID:25370308

  19. Peculiarities of the bone tissue resorption under microgravity conditions

    NASA Astrophysics Data System (ADS)

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

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

  20. 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

  1. In-vitro imaging of bone tissue and monitoring of tissue viability by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Wang, Ruikang K.; El Haj, Alicia

    2001-07-01

    Optical coherence tomography (OCT) has developed as a promising medical diagnostic imaging technology for non- invasive in situ cross-sectional imaging of biological tissues. We present this technique to image bone tissue and to monitor the redox state of mitochondria enzyme Cytochrome oxidase (CytOx) in bone for applications in tissue engineering. Superluminescent diode (SLD) with its peak emission wavelength (λ = 820nm) on the absorption band of oxidized form of CytOx was used in the experiments. The results demonstrate that the OCT system is capable of imaging the calvaria of newborn rats tomographically with a resolution at 9 microns, which could only be previously obtained by the conventional excisional biopsy. The thickness of periosteum of various calvarias from different ages of rats can be accurately determined by the system. The backscattered power-versus-depth profile form the liquid phantoms (naphthol green B with intralipid) and tissue specimens (periosteum of calvaria from newborn rats) are used to quantify the absorption changes of the sample. Absorption coefficients of naphthol green B could be quantified accurately by the linear relationship between attenuation coefficients from the slopes of the reflected signals and naphthol green B concentration. The results also show that the attenuation coefficient decreases in periosteums as CytOx being reduced by sodium dithionite, demonstrating the feasibility of this method to monitor the redox state of tissues studied.

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

    NASA Astrophysics Data System (ADS)

    Paietta, Rachel C.

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

  3. Hierarchical microimaging of bone structure and function.

    PubMed

    Müller, Ralph

    2009-07-01

    With recent advances in molecular medicine and disease treatment in osteoporosis, quantitative image processing of three-dimensional bone structures is critical in the context of bone quality assessment. Biomedical imaging technology such as MRI or CT is readily available, but few attempts have been made to expand the capabilities of these systems by integrating quantitative analysis tools and by exploring structure-function relationships in a hierarchical fashion. Nevertheless, such quantitative end points are an important factor for success in basic research and in the development of novel therapeutic strategies. CT is key to these developments, as it images and quantifies bone in three dimensions and provides multiscale biological imaging capabilities with isotropic resolutions of a few millimeters (clinical CT), a few tens of micrometers (microCT) and even as high as 100 nanometers (nanoCT). The technology enables the assessment of the relationship between microstructural and ultrastructural measures of bone quality and certain diseases or therapies. This Review focuses on presenting strategies for three-dimensional approaches to hierarchical biomechanical imaging in the study of microstructural and ultrastructural bone failure. From this Review, it can be concluded that biomechanical imaging is extremely valuable for the study of bone failure mechanisms at different hierarchical levels. PMID:19568252

  4. Solubility of Structurally Complicated Materials: II. Bone

    NASA Astrophysics Data System (ADS)

    Horvath, Ari L.

    2006-12-01

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

  5. Microsurgical Techniques Used to Construct the Vascularized and Neurotized Tissue Engineered Bone

    PubMed Central

    Fan, Junjun; Bi, Long; Jin, Dan; Wei, Kuanhai; Chen, Bin; Zhang, Zhiyong; Pei, Guoxian

    2014-01-01

    The lack of vascularization in the tissue engineered bone results in poor survival and ossification. Tissue engineered bone can be wrapped in the soft tissue flaps which are rich in blood supply to complete the vascularization in vivo by microsurgical technique, and the surface of the bone graft can be invaded with new vascular network. The intrinsic vascularization can be induced via a blood vessel or an arteriovenous loop located centrally in the bone graft by microsurgical technique. The peripheral nerve especially peptidergic nerve has effect on the bone regeneration. The peptidergic nerve can be used to construct the neurotized tissue engineered bone by implanting the nerve fiber into the center of bone graft. Thus, constructing a highly vascularized and neurotized tissue engineered bone according with the theory of biomimetics has become a useful method for repairing the large bone defect. Many researchers have used the microsurgical techniques to enhance the vascularization and neurotization of tissue engineered bone and to get a better osteogenesis effect. This review aims to summarize the microsurgical techniques mostly used to construct the vascularized and neurotized tissue engineered bone. PMID:24900962

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

    NASA Astrophysics Data System (ADS)

    Mehr, Nima Ghavidel

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

  7. Design and application of chitosan/biphasic calcium phosphate porous scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Sendemir-Urkmez, Aylin

    For the restoration of maxillofacial bone tissue, design of novel tissue engineering scaffolds capable of inducing bone remodeling through the delivery of mesenchymal stem cells (MSCs) and an angiogenic growth factor, directly at the site of the defect was investigated in order to replace autogenous cancellous bone grafts with synthetic materials. Porous, three dimensional scaffolds were fabricated by a freeze drying method. In culture media, biphasic calcium phosphate particles within chitosan produced a surface reprecipitate of a composition similar to natural apatite that led to a uniform distribution of cells and mineralized ECM through chemotaxis. Further, the reprecipitation regulated the differentiation pathway and phenotype commitment of stem cells by altering the initial cell attachment morphology and actin cytoskeleton organization. In order to induce neovascularization after implantation, constructs were designed to be loaded with gelatin microspheres that delivered basic fibroblast growth factor (bFGF), a potent angiogenic factor. In vitro proliferation tests performed on fibroblastic cells showed no detectible loss of bFGF activity when delivered through enzymatic degradation of gelatin. Laser scanning confocal microscopy was used to demonstrate that gelatin microspheres can be injected evenly into cell-scaffold constructs owing to the spongy characteristics of the scaffold. To examine the binding interactions of bFGF with surface bound gelatin, a label free biosensor system, Biomolecular INteraction Detection sensor (BIND) was used. Results confirm that the principal interaction that takes place between bFGF and gelatin is electrostatic. Cell loaded tissue engineered constructs were produced in vitro at clinically relevant sizes and implanted with and without bFGF into a porcine mandibular defect model. Tissue engineered constructs facilitated the healing of mandibular defects only if combined with delivery of bFGF via gelatin microspheres. b

  8. Fabrication and properties of porous scaffold of magnesium phosphate/polycaprolactone biocomposite for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Wu, Fan; Liu, Changsheng; O'Neill, Brian; Wei, Jie; Ngothai, Yung

    2012-07-01

    In this study, porous scaffolds made of magnesium phosphate (MP)/polycaprolactone (PCL) biocomposite were developed for bone tissue engineering applications. The composite scaffolds were fabricated by the particulate leaching method using sodium chloride particles as porogen. The obtained scaffold with porosity around 73% presents a porous structure with interconnected open pores. Hydrophilicity of the scaffolds was enhanced by the incorporation of MP component as demonstrated by the water contact angle measurement. The results of the in vitro degradation study show that the MP/PCL composite scaffolds degraded faster than PCL scaffolds in phosphate buffered saline (PBS). In addition, the degradation rate of the scaffolds could be tuned by adjusting the content of MP component in the composite. The results indicate that the MP/PCL composite scaffold has a potential application in bone tissue engineering.

  9. Designed hybrid scaffolds consisting of polycaprolactone microstrands and electrospun collagen-nanofibers for bone tissue regeneration.

    PubMed

    Lee, Hyeongjin; Yeo, Myunggu; Ahn, SeungHyun; Kang, Dong-Oan; Jang, Chul Ho; Lee, Haengnam; Park, Gil-Moon; Kim, Geun Hyung

    2011-05-01

    Biomedical scaffolds used in bone tissue engineering should have various properties including appropriate bioactivity, mechanical strength, and morphologically optimized pore structures. Collagen has been well known as a good biomaterial for various types of tissue regeneration, but its usage has been limited due to its low mechanical property and rapid degradation. In this work, a new hybrid scaffold consisting of polycaprolactone (PCL) and collagen is proposed for bone tissue regeneration. The PCL enhances the mechanical properties of the hybrid scaffold and controls the pore structure. Layered collagen nanofibers were used to enhance the initial cell attachment and proliferation. The results showed that the hybrid scaffold yielded better mechanical properties of pure PCL scaffold as well as enhanced biological activity than the pure PCL scaffold did. The effect of pore size on bone regeneration was investigated using two hybrid scaffolds with pore sizes of 200 ± 20 and 300 ± 27 μm. After post-seeding for 7 days, the cell proliferation with pore size, 200 ± 20 μm, was greater than that with pore size, 300 ± 27 μm, due to the high surface area of the scaffold. PMID:21384546

  10. Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering.

    PubMed

    Long, Teng; Yang, Jun; Shi, Shan-Shan; Guo, Ya-Ping; Ke, Qin-Fei; Zhu, Zhen-An

    2015-10-01

    An ideal scaffold for bone tissue engineering should have interconnected porous structure, good biocompatibility, and mechanical properties well-matched with natural bones. Collagen is the key component in the extracellular matrix (ECM) of natural bones, and plays an important role in bone regeneration. The biological activity of collagen has promoted it to be an advantageous biomaterial for bone tissue engineering; however, the mechanical properties of these scaffolds are insufficient and the porous structures are not stable in the wet state. An effective strategy to solve this problem is to fabricate a hybrid scaffold of biologically derived and synthetic material, which have the necessary bioactivity and mechanical stability needed for bone synthesis. In this work, a three-dimensional macroporous bone scaffold based on collagen (CO) fiber and bioglass (BG) is fabricated by a slurry-dipping technique, and its relevant mechanical and biological properties are evaluated. The CO/BG scaffold is interconnected with a porosity of 81 ± 4.6% and pore size of 40-200 μm. Compared with CO scaffold, water absorption value of CO/BG scaffold decreases greatly from 889% to 52%, which significantly alleviates the swelling behavior of collagen and improves the stability of scaffold structure. The CO/BG scaffold has a compression strength of 5.8 ± 1.6 MPa and an elastic modulus of 0.35 ± 0.01 Gpa, which are well-matched with the mechanical properties of trabecular bones. In vitro cell assays demonstrate that the CO/BG scaffold has good biocompatibility to facilitate the spreading and proliferation of human bone marrow stromal cells. Hence, the CO/BG scaffold is promising for bone tissue engineering application. PMID:25430707

  11. 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. PMID:25910818

  12. Current Concepts of Bone Tissue Engineering for Craniofacial Bone Defect Repair

    PubMed Central

    Fishero, Brian Alan; Kohli, Nikita; Das, Anusuya; Christophel, John Jared; Cui, Quanjun

    2014-01-01

    Craniofacial fractures and bony defects are common causes of morbidity and contribute to increasing health care costs. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. Current methods of repair and reconstruction include rigid fixation, grafting, and free tissue transfer. However, these methods carry innate complications, including plate extrusion, nonunion, graft/flap failure, and donor site morbidity. Recent research efforts have focused on using stem cells and synthetic scaffolds to heal critical-sized bone defects similar to those sustained from traumatic injury or ablative oncologic surgery. Growth factors can be used to augment both osteogenesis and neovascularization across these defects. Many different growth factor delivery techniques and scaffold compositions have been explored yet none have emerged as the universally accepted standard. In this review, we will discuss the recent literature regarding the use of stem cells, growth factors, and synthetic scaffolds as alternative methods of craniofacial fracture repair. PMID:25709750

  13. Developing bioactive composite scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Chen, Yun

    bone-like apatite/collagen composite coating. Saos-2 osteoblast-like cells were used to evaluate the cellular behaviors on these biomimetic coatings. Cell morphologies on the surfaces of PLLA films and scaffolds, PLLA films and scaffolds with apatite coating, and PLLA films and scaffolds with apatite/collagen composite coating were studied by SEM. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide (MTT) assay. In addition, differentiated cell function was assessed by measuring alkaline phosphatase activity. These results suggested that the apatite coating and apatite/collagen composite coating fabricated through the accelerated biomimetic processes could improve the interactions between osteoblasts and PLLA. The composite coating was more effective than apatite coating in improving such interactions. PLLA scaffolds coated with submicron collagen fibrils and submicron apatite paticulates are expected to be one of the promising 3D substrates for bone tissue engineering. To facilitate coating into scaffolds, the flowing condition was introduced into the accelerated biomimetic process. The apatite formed in the different sites in the scaffold was characterized using SEM. It was found that the accelerated biomimetic process performed in the flowing condition yielded more uniform spatial distribution of apatite particles than that in the regular shaking condition. This work provides a novel condition for obtaining uniform spatial distribution of bone-like apatite within the scaffolds in a timely manner, which is expected to facilitate uniform distribution of attached cells within the scaffoldsin vitro and in vivo.

  14. Utilizing Core–Shell Fibrous Collagen-Alginate Hydrogel Cell Delivery System for Bone Tissue Engineering

    PubMed Central

    Perez, Roman A.; Kim, Meeju; Kim, Tae-Hyun; Kim, Joong-Hyun; Lee, Jae Ho; Park, Jeong-Hui; Knowles, Jonathan C.

    2014-01-01

    Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core–shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of ∼700–1000 μm for the core and 200–500 μm for the shell area, which was largely dependent on the alginate concentration (2%–5%) as well as the injection rate (20–80 mL/h). The water uptake capacity of the core–shell carriers was as high as 98%, which could act as a pore channel to supply nutrients and oxygen to the cells. Degradation of the scaffolds showed a weight loss of ∼22% at 7 days and ∼43% at 14 days, suggesting a possible role as a degradable tissue-engineered construct. The MSCs encapsulated within the collagen core showed excellent viability, exhibiting significant cellular proliferation up to 21 days with levels comparable to those observed in the pure collagen gel matrix used as a control. A live/dead cell assay also confirmed similar percentages of live cells within the core–shell carrier compared to those in the pure collagen gel, suggesting the carrier was cell compatible and was effective for maintaining a cell population. Cells allowed to differentiate under osteogenic conditions expressed high levels of bone-related genes, including osteocalcin, bone sialoprotein, and osteopontin. Further, when the core–shell fibrous carriers were implanted in a rat calvarium defect, the bone

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

    PubMed Central

    Sun, Han; Yang, Hui-Lin

    2015-01-01

    Objective: The purpose of this study was to review the current status of calcium phosphate (CaP) scaffolds combined with bone morphogenetic proteins (BMPs) or mesenchymal stem cells (MSCs) in the field of bone tissue engineering (BTE). Date Sources: Data cited in this review were obtained primarily from PubMed and Medline in publications from 1979 to 2014, with highly regarded older publications also included. The terms BTE, CaP, BMPs, and MSC were used for the literature search. Study Selection: Reviews focused on relevant aspects and original articles reporting in vitro and/or in vivo results concerning the efficiency of CaP/BMPs or CaP/MSCs composites were retrieved, reviewed, analyzed, and summarized. Results: An ideal BTE product contains three elements: Scaffold, growth factors, and stem cells. CaP-based scaffolds are popular because of their outstanding biocompatibility, bioactivity, and osteoconductivity. However, they lack stiffness and osteoinductivity. To solve this problem, composite scaffolds of CaP with BMPs have been developed. New bone formation by CaP/BMP composites can reach levels similar to those of autografts. CaP scaffolds are compatible with MSCs and CaP/MSC composites exhibit excellent osteogenesis and stiffness. In addition, a CaP/MSC/BMP scaffold can repair bone defects more effectively than an autograft. Conclusions: Novel BTE products possess remarkable osteoconduction and osteoinduction capacities, and exhibit balanced degradation with osteogenesis. Further work should yield safe, viable, and efficient materials for the repair of bone lesions. PMID:25881610

  16. 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

  17. 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

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

    PubMed Central

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

    2016-01-01

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

  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. 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. PMID:26999521

  1. 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

  2. Calcium Phosphonate Frameworks for Treating Bone Tissue Disorders.

    PubMed

    Shi, Fa-Nian; Almeida, José C; Helguero, Luisa A; Fernandes, Maria H V; Knowles, Jonathan C; Rocha, João

    2015-10-19

    Two new examples of uncommon three-dimensional Ca-bearing metal organic frameworks, [Ca(H2O)3(HPXBP)] (CaP1) and [Ca2(H2O)2(HPXBP)1.5] (CaP2) (PXBP: p-xylylenebisphosphonate), were prepared and their structures characterized by single crystal X-ray diffraction. CaP1 crystallizes in the monoclinic C2/c space group, with three water molecules occupying a half coordination sphere on one side of the Ca atom, while CaP2 crystallizes in the triclinic P1̅ space group, with two crystallographic unique Ca atoms, each coordinated by a single water molecule. In contrast with CaP2, which exhibits very low bioactivity, CaP1 readily precipitates bone-precursor phases (octacalcium phosphate, OCP, and hydroxyapatite) in SBF solutions. Moreover, studies with MG63 osteoblast-like cells indicate that CaP1 is not toxic and stimulates bone mineralization and, thus, holds considerable potential for treating bone diseases, such as osteoporosis. PMID:26407209

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

    PubMed

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

    2013-09-01

    The purpose of this study was to develop single walled carbon nanotubes (SWCNT) and poly lactic-co-glycolic acid (PLAGA) composites for orthopedic applications and to evaluate the interaction of human stem cells (hBMSCs) and osteoblasts (MC3T3-E1 cells) via cell growth, proliferation, gene expression, extracellular matrix production and mineralization. PLAGA and SWCNT/PLAGA composites were fabricated with various amounts of SWCNT (5, 10, 20, 40, and 100 mg), characterized and degradation studies were performed. Cells were seeded and cell adhesion/morphology, growth/survival, proliferation and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated uniform incorporation of SWCNT into the PLAGA matrix and addition of SWCNT did not affect the degradation rate. Imaging studies revealed that MC3T3-E1 and hBMSCs cells exhibited normal, non-stressed morphology on the composites and all were biocompatible. Composites with 10 mg SWCNT resulted in highest rate of cell proliferation (p < 0.05) among all composites. Gene expression of alkaline phosphatase, collagen I, osteocalcin, osteopontin, Runx-2, and Bone Sialoprotein was observed on all composites. In conclusion, SWCNT/PLAGA composites imparted beneficial cellular growth capabilities and gene expression, and mineralization abilities were well established. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration and bone tissue engineering (BTE) and are promising for orthopedic applications. PMID:23629922

  4. Chitosan and alginate scaffolds for bone tissue regeneration.

    PubMed

    Olmez, S S; Korkusuz, P; Bilgili, H; Senel, S

    2007-06-01

    Polymeric scaffold for tissue regeneration was developed for veterinary applications. Oxytetracycline hydrochloride (OTC), which is a widely used antibiotic in veterinary medicine was chosen as the model compound. Gel formulations using chitosan and alginate were prepared in distilled water or in 1% (v/v) acetic acid solution. Sponges were also prepared by a freeze-drying process. Tripolyphosphate was used for cross-linking. Viscosity was decreased in the presence of OTC in chitosan gels whereas no difference was found with alginate gels. All gels showed pseudoplastic behaviour. Water absorption capacity was highest with chitosan/alginate sponges. The solvent used for preparation of the chitosan gels was found to affect the release of OTC. The release of OTC from the sponges was increased by cross-linking. Chitosan/alginate sponges showed the slowest and lowest drug release among the developed sponge formulations in this study. The formulations were found to be biocompatible, inducing no adverse reaction in vivo on surgically formed bone defects of radius of rabbits. The level of organization of the remodelled new bone in the treatment groups was better than that of control. Incorporation of OTC into formulations did not show any considerable enhancing effect. PMID:17663189

  5. Photoacoustic and ultrasound imaging of cancellous bone tissue

    NASA Astrophysics Data System (ADS)

    Yang, Lifeng; Lashkari, Bahman; Tan, Joel W. Y.; Mandelis, Andreas

    2015-07-01

    We used ultrasound (US) and photoacoustic (PA) imaging modalities to characterize cattle trabecular bones. The PA signals were generated with an 805-nm continuous wave laser used for optimally deep optical penetration depth. The detector for both modalities was a 2.25-MHz US transducer with a lateral resolution of ˜1 mm at its focal point. Using a lateral pixel size much larger than the size of the trabeculae, raster scanning generated PA images related to the averaged values of the optical and thermoelastic properties, as well as density measurements in the focal volume. US backscatter yielded images related to mechanical properties and density in the focal volume. The depth of interest was selected by time-gating the signals for both modalities. The raster scanned PA and US images were compared with microcomputed tomography (μCT) images averaged over the same volume to generate similar spatial resolution as US and PA. The comparison revealed correlations between PA and US modalities with the mineral volume fraction of the bone tissue. Various features and properties of these modalities such as detectable depth, resolution, and sensitivity are discussed.

  6. Improved prediction of rat cortical bone mechanical behavior using composite beam theory to integrate tissue level properties.

    PubMed

    Kim, Grace; Boskey, Adele L; Baker, Shefford P; van der Meulen, Marjolein C H

    2012-11-15

    Tissue level characteristics of bone can be measured by nanoindentation and microspectroscopy, but are challenging to translate to whole bone mechanical behavior in this hierarchically structured material. The current study calculated weighted section moduli from microCT attenuation values based on tissue level relationships (Z(lin,a) and Z(lin,b)) between mineralization and material properties to predict whole bone mechanical behavior. Z(lin,a) was determined using the equation of the best fit linear regression between indentation modulus from nanoindentation and mineral:matrix ratio from Raman spectroscopy. To better represent the modulus of unmineralized tissue, a second linear regression with the intercept fixed at 0 was used to calculate Z(lin,b). The predictive capability of the weighted section moduli calculated using a tissue level relationship was compared with average tissue level properties and weighted section moduli calculated using an apparent level relationship (Z(exp)) between Young's Modulus and mineralization. A range of bone mineralization was created using vitamin D deficiency in growing rats. After 10 weeks, left femurs were scanned using microCT and tested to failure in 3 point bending. Contralateral limbs were used for co-localized tissue level mechanical properties by nanoindentation and compositional measurements by Raman microspectroscopy. Vitamin D deficiency reduced whole bone stiffness and strength by ∼35% and ∼30%, respectively, but only reduced tissue mineral density by ∼10% compared with Controls. Average tissue level properties did not correlate with whole bone mechanical behavior while Z(lin,a), Z(lin,b), and Z(exp) predicted 54%, 66%, and 80% of the failure moment respectively. This study demonstrated that in a model for varying mineralization, the composite beam model in this paper is an improved method to extrapolate tissue level data to macro-scale mechanical behavior. PMID:23021607

  7. N-acetyl muramyl dipeptide stimulation of bone resorption in tissue culture.

    PubMed Central

    Dewhirst, F E

    1982-01-01

    N-Acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), a structurally defined fragment of bacterial peptidoglycan, stimulated significant release of previously incorporated 45Ca from fetal rat bones in tissue culture over the concentration range of 0.1 to 10.0 micrograms/ml. MDP-Stimulated bone resorption was not inhibited by the addition of the prostaglandin synthetase inhibitor indomethacin to the culture medium. MDP was neither mitogenic for nor stimulated the release of osteoclast-activating factor from cultured human peripheral blood mononuclear cells. Thus, MDP-stimulated bone resorption in vitro is mediated by a mechanism which is not dependent upon prostaglandins or osteoclast-activating factor. 6-O-Stearoyl-N-acetyl-muramyl-L-alanyl-D-isoglutamine, a lipophilic analog of MDP, was slightly more potent than MDP. Two diastereomers of MDP, N-acetyl-muramyl-L-alanyl-L-isoglutamine and N-acetyl-muramyl-D-alanyl-D-isoglutamine, which are inactive as adjuvants, were at least 1,000 times less active than MDP in stimulating bone resorption. The stereochemical specificity for bone-resorptive activity paralleled that required for adjuvant activity, macrophage activation, and activation of the reticuloendothelial system. PMID:7054120

  8. Bio-inspired in situ crosslinking and mineralization of electrospun collagen scaffolds for bone tissue engineering.

    PubMed

    Dhand, Chetna; Ong, Seow Theng; Dwivedi, Neeraj; Diaz, Silvia Marrero; Venugopal, Jayarama Reddy; Navaneethan, Balchandar; Fazil, Mobashar H U T; Liu, Shouping; Seitz, Vera; Wintermantel, Erich; Beuerman, Roger W; Ramakrishna, Seeram; Verma, Navin K; Lakshminarayanan, Rajamani

    2016-10-01

    Bone disorders are the most common cause of severe long term pain and physical disability, and affect millions of people around the world. In the present study, we report bio-inspired preparation of bone-like composite structures by electrospinning of collagen containing catecholamines and Ca(2+). The presence of divalent cation induces simultaneous partial oxidative polymerization of catecholamines and crosslinking of collagen nanofibers, thus producing mats that are mechanically robust and confer photoluminescence properties. Subsequent mineralization of the mats by ammonium carbonate leads to complete oxidative polymerization of catecholamines and precipitation of amorphous CaCO3. The collagen composite scaffolds display outstanding mechanical properties with Young's modulus approaching the limits of cancellous bone. Biological studies demonstrate that human fetal osteoblasts seeded on to the composite scaffolds display enhanced cell adhesion, penetration, proliferation, differentiation and osteogenic expression of osteocalcin, osteopontin and bone matrix protein when compared to pristine collagen or tissue culture plates. Among the two catecholamines, mats containing norepinephrine displayed superior mechanical, photoluminescence and biological properties than mats loaded with dopamine. These smart multifunctional scaffolds could potentially be utilized to repair and regenerate bone defects and injuries. PMID:27475728

  9. Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Feng, Kai

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

  10. Three-dimensional fiber deposition of cell-laden, viable, patterned constructs for bone tissue printing.

    PubMed

    Fedorovich, Natalja E; De Wijn, Joost R; Verbout, Abraham J; Alblas, Jacqueline; Dhert, Wouter J A

    2008-01-01

    Organ or tissue printing, a novel approach in tissue engineering, creates layered, cell-laden hydrogel scaffolds with a defined three-dimensional (3D) structure and organized cell placement. In applying the concept of tissue printing for the development of vascularized bone grafts, the primary focus lies on combining endothelial progenitors and bone marrow stromal cells (BMSCs). Here we characterize the applicability of 3D fiber deposition with a plotting device, Bioplotter, for the fabrication of spatially organized, cell-laden hydrogel constructs. The viability of printed BMSCs was studied in time, in several hydrogels, and extruded from different needle diameters. Our findings indicate that cells survive the extrusion and that their subsequent viability was not different from that of unprinted cells. The applied extrusion conditions did not affect cell survival, and BMSCs could subsequently differentiate along the osteoblast lineage. Furthermore, we were able to combine two distinct cell populations within a single scaffold by exchanging the printing syringe during deposition, indicating that this 3D fiber deposition system is suited for the development of bone grafts containing multiple cell types. PMID:18333811

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

    PubMed

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

    2016-01-01

    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. PMID:27615450

  12. Osteogenic differentiation of human bone marrow mesenchymal stem cells seeded on melt based chitosan scaffolds for bone tissue engineering applications.

    PubMed

    Costa-Pinto, Ana R; Correlo, Vitor M; Sol, Paula C; Bhattacharya, Mrinal; Charbord, Pierre; Delorme, Bruno; Reis, Rui L; Neves, Nuno M

    2009-08-10

    The purpose of this study was to evaluate the growth patterns and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) when seeded onto new biodegradable chitosan/polyester scaffolds. Scaffolds were obtained by melt blending chitosan with poly(butylene succinate) in a proportion of 50% (wt) each and further used to produce a fiber mesh scaffold. hBMSCs were seeded on those structures and cultured for 3 weeks under osteogenic conditions. Cells were able to reduce MTS and demonstrated increasing metabolic rates over time. SEM observations showed cell colonization at the surface as well as within the scaffolds. The presence of mineralized extracellular matrix (ECM) was successfully demonstrated by peaks corresponding to calcium and phosphorus elements detected in the EDS analysis. A further confirmation was obtained when carbonate and phosphate group peaks were identified in Fourier Transformed Infrared (FTIR) spectra. Moreover, by reverse transcriptase (RT)-PCR analysis, it was observed the expression of osteogenic gene markers, namely, Runt related transcription factor 2 (Runx2), type 1 collagen, bone sialoprotein (BSP), and osteocalcin. Chitosan-PBS (Ch-PBS) biodegradable scaffolds support the proliferation and osteogenic differentiation of hBMSCs cultured at their surface in vitro, enabling future in vivo testing for the development of bone tissue engineering therapies. PMID:19621927

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

    PubMed

    Cheng, Tegan L; Murphy, Ciara M; Ravarian, Roya; Dehghani, Fariba; Little, David G; Schindeler, Aaron

    2015-01-01

    Sucrose acetate isobutyrate (SAIB) is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and found synergy when co-delivering zoledronic acid (ZA) and hydroxyapatite (HA) nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP) nor Bioglass (BG) 45S5 had a significant effect on bone volume (BV) alone or in combination with the ZA. (14)C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%), and BV was further increased with ZA-adsorbed micro-HA and nano-HA (+530% and +889%). These data support the use of ZA-adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering. PMID:26668709

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

    PubMed Central

    Cheng, Tegan L; Murphy, Ciara M; Ravarian, Roya; Dehghani, Fariba; Little, David G; Schindeler, Aaron

    2015-01-01

    Sucrose acetate isobutyrate (SAIB) is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and found synergy when co-delivering zoledronic acid (ZA) and hydroxyapatite (HA) nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP) nor Bioglass (BG) 45S5 had a significant effect on bone volume (BV) alone or in combination with the ZA. 14C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%), and BV was further increased with ZA–adsorbed micro-HA and nano-HA (+530% and +889%). These data support the use of ZA–adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering. PMID:26668709

  15. Influence of structural load-bearing scaffolds on mechanical load- and BMP-2-mediated bone regeneration.

    PubMed

    McDermott, Anna M; Mason, Devon E; Lin, Angela S P; Guldberg, Robert E; Boerckel, Joel D

    2016-09-01

    A common design constraint in functional tissue engineering is that scaffolds intended for use in load-bearing sites possess similar mechanical properties to the replaced tissue. Here, we tested the hypothesis that in vivo loading would enhance bone morphogenetic protein-2 (BMP-2)-mediated bone regeneration in the presence of a load-bearing PLDL scaffold, whose pores and central core were filled with BMP-2-releasing alginate hydrogel. First, we evaluated the effects of in vivo mechanical loading on bone regeneration in the structural scaffolds. Second, we compared scaffold-mediated bone regeneration, independent of mechanical loading, with alginate hydrogel constructs, without the structural scaffold, that have been shown previously to facilitate in vivo mechanical stimulation of bone formation. Contrary to our hypothesis, mechanical loading had no effect on bone formation, distribution, or biomechanical properties in structural scaffolds. Independent of loading, the structural scaffolds reduced bone formation compared to non-structural alginate, particularly in regions in which the scaffold was concentrated, resulting in impaired functional regeneration. This is attributable to a combination of stress shielding by the scaffold and inhibition of cellular infiltration and tissue ingrowth. Collectively, these data question the necessity of scaffold similarity to mature tissue at the time of implantation and emphasize development of an environment conducive to cellular activation of matrix production and ultimate functional regeneration. PMID:27208510

  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. PMID:25995658

  17. How bone tissue and cells experience elevated temperatures during orthopaedic cutting: an experimental and computational investigation.

    PubMed

    Dolan, Eimear B; Vaughan, Ted J; Niebur, Glen L; Casey, Conor; Tallon, David; McNamara, Laoise M

    2014-02-01

    During orthopaedic surgery elevated temperatures due to cutting can result in bone injury, contributing to implant failure or delayed healing. However, how resulting temperatures are experienced throughout bone tissue and cells is unknown. This study uses a combination of experiments (forward-looking infrared (FLIR)) and multiscale computational models to predict thermal elevations in bone tissue and cells. Using multiple regression analysis, analytical expressions are derived allowing a priori prediction of temperature distribution throughout bone with respect to blade geometry, feed-rate, distance from surface, and cooling time. This study offers an insight into bone thermal behavior, informing innovative cutting techniques that reduce cellular thermal damage. PMID:24317222

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

    PubMed Central

    Sarkar, Swapan Kumar

    2015-01-01

    Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues. PMID:25995658

  19. N-methyl pyrrolidone as a potent bone morphogenetic protein enhancer for bone tissue regeneration.

    PubMed

    Miguel, Blanca San; Ghayor, Chafik; Ehrbar, Martin; Jung, Ronald E; Zwahlen, Roger A; Hortschansky, Peter; Schmoekel, Hugo G; Weber, Franz E

    2009-10-01

    In medicine, N-methyl pyrrolidone (NMP) has a long track record as a constituent in medical devices approved by the Food and Drug Administration and thus can be considered as a safe and biologically inactive small chemical. In the present study, we report on the newly discovered pharmaceutical property of NMP in enhancing bone regeneration in a rabbit calvarial defect model in vivo. At the cellular level, the pharmaceutical effect of NMP was confirmed, in particular, in combination with bone morphogenetic protein (BMP)-2, because NMP increased early and late markers for maturation of preosteoblasts and human bone marrow-derived stem cells in vitro. When we used the multipotent cell line C2C12 without autologous BMP expression, NMP alone had no effect on alkaline phosphatase activity, a marker for osteogenic transdifferentiation. Nevertheless, in combination with low BMP-2 doses, alkaline phosphatase activity was more than eight times as great. Thus, the pharmaceutical NMP mode of action is that of an enhancer of BMP activity. The dependency of the effects of NMP on BMP was confirmed in preosteoblasts because noggin, an extracellular BMP inhibitor, suppressed NMP-induced increases in early markers for osteoblast maturation in vitro. At the molecular level, NMP was shown to have no effect on the binding of BMP-2 to the ectodomain of the high-affinity BMP receptor IA. However, NMP further increased the phosphorylation of p38 and Smad1,5,8 induced by BMP-2. Thus, the small chemical NMP enhances BMP activity by increasing the kinase activity of the BMP receptor complex for Smad1,5,8 and p38 and could be employed as a potent drug for bone tissue regeneration and engineering. PMID:19320543

  20. [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. PMID:26728535

  1. [Fluid-fluid levels in bone and soft tissue tumors demonstrated by MR imaging].

    PubMed

    Sone, M; Ehara, S; Sasaki, M; Nakasato, T; Tamakawa, Y; Shiraishi, H; Abe, M

    1992-08-25

    Fluid-fluid levels in bone tumors have been described in aneurysmal bone cysts and other cystic tumors of bones and soft tissue tumors. We experienced three bone tumors (simple bone cyst, bone metastasis, and osteosarcoma) and three soft tissue tumors (fibrosarcoma, two cases of cavernous hemangioma) that showed fluid-fluid levels on MR, and investigated their cause. Causes included blood in the cystic spaces, hemorrhage in the tumor, the telangiectatic component of the osteosarcoma, and the cavernous component of the hemangioma. No specific diagnosis could be made based on the finding of fluid-fluid levels. We conclude that fluid-fluid levels on MR are rather nonspecific findings in bone and soft tissue tumors and that the diagnosis should be made on the basis of other radiological and clinical findings. PMID:1408681

  2. Nanohydroxyapatite/poly(ester urethane) scaffold for bone tissue engineering.

    PubMed

    Boissard, C I R; Bourban, P-E; Tami, A E; Alini, M; Eglin, D

    2009-11-01

    Biodegradable viscoelastic poly(ester urethane)-based scaffolds show great promise for tissue engineering. In this study, the preparation of hydroxyapatite nanoparticles (nHA)/poly(ester urethane) composite scaffolds using a salt-leaching-phase inverse process is reported. The dispersion of nHA microaggregates in the polymer matrix were imaged by microcomputed X-ray tomography, allowing a study of the effect of the nHA mass fraction and process parameters on the inorganic phase dispersion, and ultimately the optimization of the preparation method. How the composite scaffold's geometry and mechanical properties change with the nHA mass fraction and the process parameters were assessed. Increasing the amount of nHA particles in the composite scaffold decreased the porosity, increased the wall thickness and consequently decreased the pore size. The Young's modulus of the poly(ester urethane) scaffold was improved by 50% by addition of 10 wt.% nHA (from 0.95+/-0.5 to 1.26+/-0.4 MPa), while conserving poly(ester urethane) viscoelastic properties and without significant changes in the scaffold macrostructure. Moreover, the process permitted the inclusion of nHA particles not only in the poly(ester urethane) matrix, but also at the surface of the scaffold pores, as shown by scanning electron microscopy. nHA/poly(ester urethane) composite scaffolds have great potential as osteoconductive constructs for bone tissue engineering. PMID:19442765

  3. 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

    2016-01-01

    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. PMID:27187017

  4. Higher Doses of Bisphosphonates Further Improve Bone Mass, Architecture, and Strength but Not the Tissue Material Properties in Aged Rats

    PubMed Central

    Shahnazari, Mohammad; Yao, Wei; Dai, WeiWei; Wang, Bob; Ionova-Martin, Sophi S.; Ritchie, Robert O.; Heeren, Daniel; Burghardt, Andrew J.; Nicolella, Daniel P.; Kimiecik, Michael G.; Lane, Nancy E.

    2010-01-01

    We report the results of a series of experiments designed to determine the effects of ibandronate (Ibn) and risedronate (Ris) on a number of bone quality parameters in aged osteopenic rats to explain how bone material and bone mass may be affected by the dose of bisphosphonates (BP) and contribute to their anti-fracture efficacy. Eighteen-month old female rats underwent either ovariectomy or sham surgery. The ovariectomized (OVX) groups were left untreated for 2 months to develop osteopenia. Treatments started at 20 months of age as follows: sham and OVX control (treated with saline), OVX+risedronate 30 and 90 (30 or 90 μg/kg/dose), and OVX+ibandronate 30 and 90 (30 or 90 μg/kg/dose). The treatments were given monthly for four months by subcutaneous injection. At sacrifice at 24 months of age the 4th lumbar vertebra was used for μCT scans (bone mass, architecture, and degree of mineralization of bone, DMB) and histomorphometry, and the 6th lumbar vertebra, tibia, and femur were collected for biomechanical testing to determine bone structural and material strength, cortical fracture toughness, and tissue elastic modulus. The compression testing of the vertebral bodies (LVB6) was simulated using finite-element analysis (FEA) to also estimate the bone structural stiffness. Both Ibn and Ris dose-dependently increased bone mass and improved vertebral bone microarchitecture and mechanical properties compared to OVX control. Estimates of vertebral maximum stress from FEA were correlated with vertebral maximum load (r=0.5, p<0.001) and maximum stress (r=0.4, p<0.005) measured experimentally. Tibial bone bending modulus and cortical strength increased compared to OVX with both BP but no dose-dependent effect was observed. DMB and elastic modulus of trabecular bone were improved with Ibn30 compared to OVX but were not affected in other BP-treated groups. DMB of tibial cortical bone showed no change with BP treatments. The fracture toughness examined in midshaft femurs did

  5. 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

  6. 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.

  7. Activity vs. rest in the treatment of bone, soft tissue and joint injuries.

    PubMed Central

    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

  8. Biological and biophysical principles in extracorporal bone tissue engineering. Part I.

    PubMed

    Meyer, U; Joos, U; Wiesmann, H P

    2004-06-01

    Advances in the field of bone tissue engineering have encouraged physicians to introduce these techniques into clinical practice. Bone tissue engineering is the construction, repair or replacement of damaged or missing bone in humans or animals. Engineering of bone can take place within the animal body or extracorporal in a bioreactor for later grafting into the body. Appropriate cell types and non-living substrata are minimal requirements for an extracorporal tissue engineering approach. This review discusses the biological and biophysical background of in vitro bone tissue engineering. Biochemical and biophysical stimuli of cell growth and differentiation are regarded as potent tools to improve bone formation in vitro. The paper focuses on basic principles in extracorporal engineering of bone-like tissues, intended to be implanted in animal experiments and clinical studies. Particular attention is given in this part to the contributions of cell and material science to the development of bone-like tissues. Several approaches are at the level of clinical applicability and it can be expected that widespread use of engineered bone constructs will change the surgeon's work in the near future. PMID:15145032

  9. Magnetic Hydroxyapatite Bone Substitutes to Enhance Tissue Regeneration: Evaluation In Vitro Using Osteoblast-Like Cells and In Vivo in a Bone Defect

    PubMed Central

    Panseri, Silvia; Cunha, Carla; D'Alessandro, Teresa; Sandri, Monica; Russo, Alessandro; Giavaresi, Gianluca; Marcacci, Maurilio; Hung, Clark T.; Tampieri, Anna

    2012-01-01

    In case of degenerative disease or lesion, bone tissue replacement and regeneration is an important clinical goal. In particular, nowadays, critical size defects rely on the engineering of scaffolds that are 3D structural supports, allowing cellular infiltration and subsequent integration with the native tissue. Several ceramic hydroxyapatite (HA) scaffolds with high porosity and good osteointegration have been developed in the past few decades but they have not solved completely the problems related to bone defects. In the present study we have developed a novel porous ceramic composite made of HA that incorporates magnetite at three different ratios: HA/Mgn 95/5, HA/Mgn 90/10 and HA/Mgn 50/50. The scaffolds, consolidated by sintering at high temperature in a controlled atmosphere, have been analysed in vitro using human osteoblast-like cells. Results indicate high biocompatibility, similar to a commercially available HA bone graft, with no negative effects arising from the presence of magnetite or by the use of a static magnetic field. HA/Mgn 90/10 was shown to enhance cell proliferation at the early stage. Moreover, it has been implanted in vivo in a critical size lesion of the rabbit condyle and a good level of histocompatibility was observed. Such results identify this scaffold as particularly relevant for bone tissue regeneration and open new perspectives for the application of a magnetic field in a clinical setting of bone replacement, either for magnetic scaffold fixation or magnetic drug delivery. PMID:22685602

  10. Development of a 3D polymer reinforced calcium phosphate cement scaffold for cranial bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Alge, Daniel L.

    The repair of critical-sized cranial bone defects represents an important clinical challenge. The limitations of autografts and alloplastic materials make a bone tissue engineering strategy desirable, but success depends on the development of an appropriate scaffold. Key scaffold properties include biocompatibility, osteoconductivity, sufficient strength to maintain its structure, and resorbability. Furthermore, amenability to rapid prototyping fabrication methods is desirable, as these approaches offer precise control over scaffold architecture and have the potential for customization. While calcium phosphate cements meet many of these criteria due to their composition and their injectability, which can be leveraged for scaffold fabrication via indirect casting, their mechanical properties are a major limitation. Thus, the overall goal of this work was to develop a 3D polymer reinforced calcium phosphate cement scaffold for use in cranial bone tissue engineering. Dicalcium phosphate dihydrate (DCPD) setting cements are of particular interest because of their excellent resorbability. We demonstrated for the first time that DCPD cement can be prepared from monocalcium phosphate monohydrate (MCPM)/hydroxyapatite (HA) mixtures. However, subsequent characterization revealed that MCPM/HA cements rapidly convert to HA during degradation, which is undesirable and led us to choose a more conventional formulation for scaffold fabrication. In addition, we developed a novel method for calcium phosphate cement reinforcement that is based on infiltrating a pre-set cement structure with a polymer, and then crosslinking the polymer in situ. Unlike prior methods of cement reinforcement, this method can be applied to the reinforcement of 3D scaffolds fabricated by indirect casting. Using our novel method, composites of poly(propylene fumarate) (PPF) reinforced DCPD were prepared and demonstrated as excellent candidate scaffold materials, as they had increased strength and ductility

  11. An adhesive bone marrow scaffold and bone morphogenetic-2 protein carrier for cartilage tissue engineering.

    PubMed

    Simson, Jacob A; Strehin, Iossif A; Lu, Qiaozhi; Uy, Manuel O; Elisseeff, Jennifer H

    2013-03-11

    A chondroitin sulfate-bone marrow (CS-BM) adhesive hydrogel was used to localize rhBMP-2 to enhance articular cartilage tissue formation. Chondrocyte pellet culture revealed that 0.1 and 1 μg/mL of rhBMP-2 enhanced sulfated-GAG content. rhBMP-2 localization within the hydrogels was investigated, and it was found that BM, CS-NHS, and rhBMP-2 levels and time affected rhBMP-2 retention. Retention was modulated from 82 to 99% over a 3-week period for the material formulations investigated. To evaluate carrier efficacy, rhBMP-2 and bovine articular chondrocytes were encapsulated within CS-BM, and biochemical evaluation revealed significant increases in total collagen production with rhBMP-2. Histological analysis revealed more robust tissue formation and greater type-II collagen production with encapsulated rhBMP-2. Subsequently, a subcutaneous culture of hydrogels revealed increased total collagen, type-II to type-I collagen ratio, and sulfated GAG in samples carrying rhBMP-2. These findings indicate the development of a multifunctional system capable of localizing rhBMP-2 to enhance repair tissue quality. PMID:23320412

  12. 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. PMID:11543035

  13. 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.

  14. High rate properties of porcine skull bone tissue

    NASA Astrophysics Data System (ADS)

    Herwig, Kyle Jeffry

    Several recent studies have shown the importance of understanding the nature of blast injuries. Traditionally, the lungs and other air filled organs were the focus of these injuries but it is being discovered that some level of brain trauma may result after encountering a blast. These injuries are referred to as traumatic brain injuries, or TBI. There has been many clinical studies and statistical analyses done concerning these injuries, but there is still no physical understanding of the problem. In order to develop a model of how this injury can occur, rate dependent material properties of the tissues the stress wave will travel through are needed. In this study, the compressive response of porcine skull bone through the thickness direction was experimentally determined over a wide range of rates, ranging from 0.001 sec -1 to approximately 3000 sec-1. The results reveal that for most mechanical properties there is a clear rate dependence of the material. However, only one subset of the skull section appeared to have a rate dependent initial modulus, with the rest showing no significant statistical dependence on loading rate. Other mechanical properties appeared to be affected by the loading rate, including the strain energy density.

  15. Vascularized Bone Tissue Formation Induced by Fiber-Reinforced Scaffolds Cultured with Osteoblasts and Endothelial Cells

    PubMed Central

    Liu, Xinhui; Zhang, Guoping; Hou, Chuanyong; Wang, Hua; Yang, Yelin; Guan, Guoping; Dong, Wei; Gao, Hongyang

    2013-01-01

    The repair of the damaged bone tissue caused by damage or bone disease was still a problem. Current strategies including the use of autografts and allografts have the disadvantages, namely, diseases transmission, tissue availability and donor morbidity. Bone tissue engineering has been developed and regarded as a new way of regenerating bone tissues to repair or substitute damaged or diseased ones. The main limitation in engineering in vitro tissues is the lack of a sufficient blood vessel system, the vascularization. In this paper, a new-typed hydroxyapatite/collagen composite scaffold which was reinforced by chitosan fibers and cultured with osteoblasts and endothelial cells was fabricated. General observation, histological observation, detection of the degree of vascularization, and X-ray examination had been done to learn the effect of vascularized bone repair materials on the regeneration of bone. The results show that new vessel and bone formed using implant cultured with osteoblasts and endothelial cells. Nanofiber-reinforced scaffold cultured with osteoblasts and endothelial cells can induce vascularized bone tissue formation. PMID:24369019

  16. 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.

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

    PubMed Central

    2014-01-01

    Background In fracture treatment, adequate fixation of implants is crucial to long-term clinical performance. Bisphosphonates (BP), potent inhibitors of osteoclastic bone resorption, are known to increase peri-implant bone mass and accelerate primary fixation. However, adverse effects are associated with systemic use of BPs. Thus, Zoledronic acid (ZOL) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site. Methods ZOL was immobilized on fibrinogen coated titanium screws. Using a bilateral approach, ZOL loaded test and non-loaded control screws were implanted into femoral condyle bone defects, created by an overdrilling technique. Histological analyses of the local tissue effects such as new bone formation and osteointegration were performed at days 1, 5 and 10. Results Histological evaluation of the five day ZOL group, demonstrated a higher osseous differentiation trend. At ten days an early influx of mesenchymal and osteoprogenitor cells was seen and a higher level of cellular proliferation and differentiation (p < 5%). In the ZOL group bone-to-screw contact and bone volume values within the defect tended to increase. Local drug release did not induce any adverse cellular effects. Conclusion This study indicates that local ZOL delivery into a compromised cancellous bone site actively supports peri-implant osteogenesis, positively affecting mesenchymal cells, at earlier time points than previously reported in the literature. PMID:24656151

  18. Tooth and bone deformation: structure and material properties by ESPI

    NASA Astrophysics Data System (ADS)

    Zaslansky, Paul; Shahar, Ron; Barak, Meir M.; Friesem, Asher A.; Weiner, Steve

    2006-08-01

    In order to understand complex-hierarchical biomaterials such as bones and teeth, it is necessary to relate their structure and mechanical-properties. We have adapted electronic speckle pattern-correlation interferometry (ESPI) to make measurements of deformation of small water-immersed specimens of teeth and bones. By combining full-field ESPI with precision mechanical loading we mapped sub-micron displacements and determined material-properties of the samples. By gradually and elastically compressing the samples, we compensate for poor S/N-ratios and displacement differences of about 100nm were reliably determined along samples just 2~3mm long. We produced stress-strain curves well within the elastic performance range of these materials under biologically relevant conditions. For human tooth-dentin, Young's modulus in inter-dental areas of the root is 40% higher than on the outer sides. For cubic equine bone samples the compression modulus of axial orientations is about double the modulus of radial and tangential orientations (20 GPa versus 10 GPa respectively). Furthermore, we measured and reproduced a surprisingly low Poisson's ratio, which averaged about 0.1. Thus the non-contact and non-destructive measurements by ESPI produce high sensitivity analyses of mechanical properties of mineralized tissues. This paves the way for mapping deformation-differences of various regions of bones, teeth and other biomaterials.

  19. 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. PMID:24704262

  20. The Resistance of Cortical Bone Tissue to Failure under Cyclic Loading is Reduced with Alendronate

    PubMed Central

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

    2014-01-01

    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, 1.0 mg/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, ×103 µm2; p<0.01) and the density of osteocyte lacunae (−20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×102 #/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. PMID:24704262

  1. Fabrication of gelatin-strontium substituted calcium phosphate scaffolds with unidirectional pores for bone tissue engineering.

    PubMed

    Wu, Yu-Chun; Lin, Wei-Yu; Yang, Chyun-Yu; Lee, Tzer-Min

    2015-03-01

    This study fabricated homogeneous gelatin-strontium substituted calcium phosphate composites via coprecipitation in a gelatin solution. Unidirectional porous scaffolds with an oriented microtubular structure were then manufactured using freeze-drying technology. The resulting structure and pore alignment were determined using scanning electron microscopy. The pore size were in the range of 200-400 μm, which is considered ideal for the engineering of bone tissue. The scaffolds were further characterized using energy dispersive spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Hydroxyapatite was the main calcium phosphate compound in the scaffolds, with strontium incorporated into the crystal structure. The porosity of the scaffolds decreased with increasing concentration of calcium-phosphate. The compressive strength in the longitudinal direction was two to threefold higher than that observed in the transverse direction. Our results demonstrate that the composite scaffolds degraded by approximately 20 % after 5 weeks. Additionally, in vitro results reveal that the addition of strontium significantly increased human osteoblastic cells proliferation. Scaffolds containing strontium with a Sr-CaP/(gelatin + Sr-CaP) ratio of 50 % provided the most suitable environment for cell proliferation, particularly under dynamic culture conditions. This study demonstrates the considerable potential of composite scaffolds composed of gelatin-strontium-substituted calcium phosphate for applications in bone tissue engineering. PMID:25773230

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

    PubMed

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

    2015-10-01

    Mg-Zn-Zr alloy cylinders were implanted into the femoral condyles of Japanese big-ear white rabbits. X-ray showed that by 12 weeks following implantation the implant became obscure, around which the low-density area appeared and enlarged. By 24 weeks, the implant was more obscure and the density of the surrounding cancellous bone increased. Scanning electron microscopy examination showed bone tissue on the surface of the alloy attached by living fibers at 12 weeks. Micro-CT confirmed that new bone tissue on the surface of the residual alloy implant increased from 12 weeks to 24 weeks. By 12 weeks, many cavities in the cancellous bone tissue around the implant were noted with a CT value, similar to gas value, and increasing by 24 weeks (P<0.01). Histological examination of hard tissue slices showed that bone tissue was visibly attached to the alloy in the femoral condyle at 12 weeks. The trabecular bone tissues became more intact and dense, and the cavities were filled with soft tissue at 24 weeks. In general, gas produced by the degradation of the Mg-Zn-Zr alloy can cause cavitation within cancellous bone, which does not affect osteogenesis of Mg alloy. PMID:26117789

  3. Bone Tissue Engineering Using High Permeability Poly-epsilon-caprolactone Scaffolds Conjugated with Bone Morphogenetic Protein-2

    NASA Astrophysics Data System (ADS)

    Mitsak, Anna Guyer

    Bone is the second most commonly transplanted tissue in the United States. Limitations of current bone defect treatment options include morbidity at the autograft harvest site, mechanical failure, and poorly controlled growth factor delivery. Combining synthetic scaffolds with biologics may address these issues and reduce dependency on autografts. The ideal scaffolding system should promote tissue in-growth and nutrient diffusion, control delivery of biologics and maintain mechanical integrity during bone formation. This dissertation evaluates how scaffold permeability, conjugated bone morphogenetic protein-2 (BMP-2) and differentiation medium affect osteogenesis in vitro and bone growth in vivo.. "High" and "low" permeability polycaprolactone (PCL) scaffolds with regular architectures were manufactured using solid free form fabrication. Bone growth in vivo was evaluated in an ectopic mouse model. High permeability scaffolds promoted better 8 week bone growth, supported tissue penetration into the scaffold core, and demonstrated increased mechanical properties due to newly formed bone. Next, the effects of differentiation medium and conjugated BMP-2 on osteogenesis were compared. Conjugation may improve BMP-2 loading efficiency, help localize bone growth and control release. High permeability scaffolds were conjugated with BMP-2 using the crosslinker, sulfo-SMCC. When adipose-derived and bone marrow stromal cells were seeded onto constructs (with or without BMP-2), BMSC expressed more differentiation markers, and differentiation medium affected differentiation more than BMP-2. In vivo, scaffolds with ADSC pre-differentiated in osteogenic medium (with and without BMP-2) and scaffolds with only BMP-2 grew the most bone. Bone volume did not differ among these groups, but constructs with ADSC had evenly distributed, scaffold-guided bone growth. Analysis of two additional BMP-2 attachment methods (heparin and adsorption) showed highest conjugation efficiency for the

  4. Bone tissue engineering: the role of interstitial fluid flow

    NASA Technical Reports Server (NTRS)

    Hillsley, M. V.; Frangos, J. A.

    1994-01-01

    It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

  5. Apparent- and Tissue-Level Yield Behaviors of L4 Vertebral Trabecular Bone and Their Associations with Microarchitectures.

    PubMed

    Gong, He; Wang, Lizhen; Fan, Yubo; Zhang, Ming; Qin, Ling

    2016-04-01

    The precise quantification of vertebral trabecular bone strength and the associations between the microarchitecture and nonlinear mechanics of trabecular bone under various loading conditions may provide insights into trabecular bone quality and trabecular strength prediction based on microarchitectures. In this research, 44 cubic L4 vertebral trabecular bone specimens (5 × 5 × 5 mm(3)) were selected from six male Chinese donors aged 62-70 years. For each vertebral trabecular cube, micro-computed tomography image-based nonlinear micro-finite element analyzes were conducted under compressive and tensile loadings along two orthogonal directions. A bilinear tissue constitutive model was used to describe the nonlinearity of bone tissue material. In each analysis, apparent Young's modulus and initial apparent yield point were determined; the average tissue von Mises stress at the apparent yield point was also calculated, and the amount of tissue elements yielded was obtained. Principal components (PCs) analysis revealed three independent components of the microarchitectural parameters of the vertebral trabecular bones; these three PCs can account for 80.744% of the total variability of trabecular microarchitectures; the first PC (PC1) included bone volume fraction, connectivity density and trabecular number; the second PC (PC2) comprised structure model index and degree of anisotropy; and the third PC (PC3) represented trabecular thickness and age. Multivariate linear regression analysis showed that the PCs were strongly predictive of the apparent- and tissue-level mechanical parameters of the vertebral trabecular bone. To gain further insights into the mechanical properties of trabecular bone, we divided the six vertebral bodies into two groups based on the microarchitectural parameters: high-quality group and low-quality group. We then compared the differences in the mechanical parameters between tension and compression, as well as along longitudinal and

  6. 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. PMID:27022489

  7. 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

  8. 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.

  9. Quantification of Age-Related Tissue-Level Failure Strains of Rat Femoral Cortical Bones Using an Approach Combining Macrocompressive Test and Microfinite Element Analysis.

    PubMed

    Fan, Ruoxun; Gong, He; Zhang, Rui; Gao, Jiazi; Jia, Zhengbin; Hu, Yanjuan

    2016-04-01

    Bone mechanical properties vary with age; meanwhile, a close relationship exists among bone mechanical properties at different levels. Therefore, conducting multilevel analyses for bone structures with different ages are necessary to elucidate the effects of aging on bone mechanical properties at different levels. In this study, an approach that combined microfinite element (micro-FE) analysis and macrocompressive test was established to simulate the failure of male rat femoral cortical bone. Micro-FE analyses were primarily performed for rat cortical bones with different ages to simulate their failure processes under compressive load. Tissue-level failure strains in tension and compression of these cortical bones were then back-calculated by fitting the experimental stress-strain curves. Thus, tissue-level failure strains of rat femoral cortical bones with different ages were quantified. The tissue-level failure strain exhibited a biphasic behavior with age: in the period of skeletal maturity (1-7 months of age), the failure strain gradually increased; when the rat exceeded 7 months of age, the failure strain sharply decreased. In the period of skeletal maturity, both the macro- and tissue-levels mechanical properties showed a large promotion. In the period of skeletal aging (9-15 months of age), the tissue-level mechanical properties sharply deteriorated; however, the macromechanical properties only slightly deteriorated. The age-related changes in tissue-level failure strain were revealed through the analysis of male rat femoral cortical bones with different ages, which provided a theoretical basis to understand the relationship between rat cortical bone mechanical properties at macro- and tissue-levels and decrease of bone strength with age. PMID:26902102

  10. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche1

    PubMed Central

    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.

    2015-01-01

    BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. PMID:26696367

  11. [Genetic Aberration and Pathological Diagnosis in Bone and Soft-Tissue Tumors].

    PubMed

    Iura, Kunio; Oda, Yoshinao

    2016-03-01

    Bone and soft-tissue sarcomas comprise a rare, complex, and heterogeneous group of tumors for which it is difficult for even experienced pathologists to provide a conclusive diagnosis. The number of diagnoses made using genetic analysis has increased since the detection of fusion genes in several soft-tissue tumors in the 1990s. Moreover, other specific genetic aberrations have been reported in various bone and soft-tissue tumors. In addition, molecular therapeutic targets have been sought in advanced cases of soft-tissue and bone tumors similar to other organ malignancies. To enable the pathological diagnosis of bone and soft-tissue tumors, it is necessary to combine histological diagnosis with immunohistochemistry and gene analysis findings including fusion gene or other genetic aberrations. In this review, we describe the fusion genes recently reported in bone and soft-tissue tumors such as solitary fibrous tumor, aneurysmal bone cyst, nodular fasciitis, CIC-DUX4 fusion gene-positive small round cell tumors, or BCOR-CCNB3-positive sarcoma as well as other genetic aberrations in dedifferentiated liposarcoma, malignant rhabdoid tumor, cartilaginous tumor, Langerhans cell histiocytosis chondroblastoma, or giant cell tumor of the bone. We also demonstrate their association with pathological diagnosis. PMID:27067846

  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. Application of new optical coherence elastography to monitor the mineralization processing in bone tissue engineering constructs

    NASA Astrophysics Data System (ADS)

    Guan, Guangying; Song, Shaozhen; Huang, Zhihong; Yang, Ying

    2015-03-01

    Generation of functional tissue in vitro through tissue engineering technique is a promising direction to repair and replace malfunctioned organ and tissue in the modern medicine for various diseases which could not been treated well by conventional therapy. Similar to the embryo development, the generation of tissue in vitro is a highly dynamic processing. Obtaining the feedback of the processing real time is highly demanded. In this study, a new methodology has been explored aiming to monitor the morphological and mechanical property alteration of bone tissue engineering constructs simultaneously. Optical coherence elastography (OCE) equipped with a LDS V201 permanent magnet shaker and a modulated acoustic radiation force (ARF) to provide a vibration signal, has been used for the real time and non-destructive monitoring. A phantom construct system has been used to optimize the measurement conditions in which agar hydrogel with concentration from 0, 0.75 to 2% with/without hydroxyappatite particles have been injected to 3D porous poly (lactic acid) scaffolds to simulate the collagenous extracellular matrix (ECM) and mineralized ECM. The structural and elastography images of the constructs have clearly demonstrated the linear relation with the increased mechanical property versus the increase of agar concentration within the pores of the scaffolds. The MG63 bone cells seeded in the scaffolds and cultured for 4 weeks have been monitored by the established protocol exhibiting the increased mechanical strength in the pore wall where the ECM or mineralized ECM was assumed to be formed in comparison to empty pores. This study confirms that OCE-ARF could become a valuable tool in regenerative medicine to assess the biological events during in vitro culture and conditioning.

  14. In vivo assessment of new resorbable PEG-PPG-PEG copolymer/starch bone wax in bone healing and tissue reaction of bone defect in rabbit model.

    PubMed

    Suwanprateeb, J; Kiertkrittikhoon, S; Kintarak, J; Suvannapruk, W; Thammarakcharoen, F; Rukskul, P

    2014-09-01

    In this study, in vivo performance of novel resorbable bone wax based on a miscible blend between PEG-PPG-PEG copolymer mixtures and pregelatinized starch at 0 and 25 percent by weight including hemostasis, tissue reaction and bone healing in a non-critical size tibia defect model were assessed and compared with commercial non-resorbable bone wax. Systemic reaction was evaluated by blood chemistry while local reaction, bone quantity and quality were evaluated by microcomputed tomography (microCT) and histology analyses. It was observed that the resorbable bone waxes did not show any adverse systemic reaction and resorbed from the defects within approximately 2 days after application. They were as effective as the commercial bone wax in hemostasis, but provided better adherence to the bone surface. The incorporation of pre-gelatinized starch in the formulation could further help in improved molding texture and decreased glove adherence. MicroCT and histology analyses showed that the resorbable bone waxes did not inhibit the osteogenesis whereas commercial bone wax impaired bone healing and displayed inflammation and foreign body reactions. PMID:24913421

  15. Multiscale mechanics of hierarchical structure/property relationships in calcified tissues and tissue/material interfaces

    PubMed Central

    Katz, J. Lawrence; Misra, Anil; Spencer, Paulette; Wang, Yong; Bumrerraj, Sauwanan; Nomura, Tsutomu; Eppell, Steven J.; Tabib-Azar, Massood

    2007-01-01

    This paper presents a review plus new data that describes the role hierarchical nanostructural properties play in developing an understanding of the effect of scale on the material properties (chemical, elastic and electrical) of calcified tissues as well as the interfaces that form between such tissues and biomaterials. Both nanostructural and microstructural properties will be considered starting with the size and shape of the apatitic mineralites in both young and mature bovine bone. Microstructural properties for human dentin and cortical and trabecular bone will be considered. These separate sets of data will be combined mathematically to advance the effects of scale on the modeling of these tissues and the tissue/biomaterial interfaces as hierarchical material/structural composites. Interfacial structure and properties to be considered in greatest detail will be that of the dentin/adhesive (d/a) interface, which presents a clear example of examining all three material properties, (chemical, elastic and electrical). In this case, finite element modeling (FEA) was based on the actual measured values of the structure and elastic properties of the materials comprising the d/a interface; this combination provides insight into factors and mechanisms that contribute to premature failure of dental composite fillings. At present, there are more elastic property data obtained by microstructural measurements, especially high frequency ultrasonic wave propagation (UWP) and scanning acoustic microscopy (SAM) techniques. However, atomic force microscopy (AFM) and nanoindentation (NI) of cortical and trabecular bone and the dentin–enamel junction (DEJ) among others have become available allowing correlation of the nanostructural level measurements with those made on the microstructural level. PMID:18270549

  16. Image-Guided Percutaneous Ablation of Bone and Soft Tissue Tumors

    PubMed Central

    Kurup, A. Nicholas; Callstrom, Matthew R.

    2010-01-01

    Image-guided percutaneous ablation of bone and soft tissue tumors is an effective minimally invasive alternative to conventional therapies, such as surgery and external beam radiotherapy. Proven applications include treatment of benign primary bone tumors, particularly osteoid osteoma, as well as palliation of painful bone metastases. Use of percutaneous ablation in combination with cementoplasty can provide stabilization of metastases at risk for fracture. Local control of oligometastatic disease and treatment of desmoid tumors are emerging applications. PMID:22550367

  17. Effect of cadmium on bone tissue in growing animals.

    PubMed

    Rodríguez, Juliana; Mandalunis, Patricia Mónica

    2016-08-01

    Accumulation of cadmium (Cd), an extremely toxic metal, can cause renal failure, decreased vitamin D synthesis, and consequently osteoporosis. The aim of this work was to evaluate the effect of Cd on two types of bone in growing Wistar rats. Sixteen 21-day-old male Wistar rats were assigned to one of two groups. The Cd group subcutaneously received 0.5mg/kg of CdCl2 5 times weekly for 3 months. The control group similarly received bidistilled water. Following euthanasia, the mandibles and tibiae were resected, fixed, decalcified and processed histologically to obtain sections for H&E and tartrate-resistant acid phosphatase (TRAP) staining. Photomicrographs were used to determine bone volume (BV/TV%), total growth cartilage width (GPC.Wi) hypertrophic cartilage width (HpZ.Wi), percentage of yellow bone marrow (%YBM), megakaryocyte number (N.Mks/mm(2)), and TRAP+osteoclast number (N.TRAP+Ocl/mm(2)). Results were statistically analyzed using Student's t test. Cd exposed animals showed a significant decrease in subchondral bone volume and a significant increase in TRAP+ osteoclast number and percentage of yellow bone marrow in the tibia, and an increase in megakaryocyte number in mandibular interradicular bone. No significant differences were observed in the remaining parameters. The results obtained with this experimental design show that Cd would seemingly have a different effect on subchondral and interradicular bone. The decrease in bone volume and increase in tibial yellow bone marrow suggest that cadmium inhibits differentiation of mesenchymal cells to osteoblasts, favoring differentiation into adipocytes. The different effects of Cd on interradicular bone might be due to the protective effect of the mastication forces. PMID:27312893

  18. Tomographic reconstruction of layered tissue structures

    NASA Astrophysics Data System (ADS)

    Hielscher, Andreas H.; Azeez-Jan, Mohideen; Bartel, Sebastian

    2001-11-01

    In recent years the interest in the determination of optical properties of layered tissue structure has resurfaced. Applications include, for example, studies on layered skin tissue and underlying muscles, imaging of the brain underneath layers of skin, skull, and meninges, and imaging of the fetal head in utero beneath the layered structures of the maternal abdomen. In this work we approach the problem of layered structures in the framework of model-based iterative image reconstruction schemes. These schemes are currently developed to determine the optical properties inside tissue from measurement on the surface. If applied to layered structure these techniques yield substantial improvements over currently available semi-analytical approaches.

  19. Effect of random microstructure on crack propagation in cortical bone tissue under dynamic loading

    NASA Astrophysics Data System (ADS)

    Gao, X.; Li, S.; Adel-Wahab, A.; Silberschmidt, V.

    2013-07-01

    A fracture process in a cortical bone tissue depends on various factors, such as bone loss, heterogeneous microstructure, variation of its material properties and accumulation of microcracks. Therefore, it is crucial to comprehend and describe the effect of microstructure and material properties of the components of cortical bone on crack propagation in a dynamic loading regime. At the microscale level, osteonal bone demonstrates a random distribution of osteons imbedded in an interstitial matrix and surrounded by a thin layer known as cement line. Such a distribution of osteons can lead to localization of deformation processes. The global mechanical behavior of bone and the crack-propagation process are affected by such localization under external loads. Hence, the random distribution of microstructural features plays a key role in the fracture process of cortical bone. The purpose of this study is two-fold: firstly, to develop two-dimensional microstructured numerical models of cortical bone tissue in order to examine the interaction between the propagating crack and bone microstructure using an extended finite-element method under both quasi-static and dynamic loading conditions; secondly, to investigate the effect of randomly distributed microstructural constituents on the crack propagation processes and crack paths. The obtained results of numerical simulations showed the influence of random microstructure on the global response of bone tissue at macroscale and on the crack-propagation process for quasi-static and dynamic loading conditions.

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

    PubMed

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

    2015-01-01

    A current goal of dental implant research is the development of titanium (Ti) surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration. Objective The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments. Material and Methods Surface treatments consisted of 20% N2 and 80% H2, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses. Results Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area. Conclusion Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces. PMID:25760262

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

    PubMed Central

    FERRAZ, Emanuela Prado; SVERZUT, Alexander Tadeu; FREITAS, Gileade Pereira; SÁ, Juliana Carvalho; ALVES, Clodomiro; BELOTI, Marcio Mateus; ROSA, Adalberto Luiz

    2015-01-01

    A current goal of dental implant research is the development of titanium (Ti) surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration. Objective The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments. Material and Methods Surface treatments consisted of 20% N2 and 80% H2, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses. Results Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area. Conclusion Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces. PMID:25760262

  2. Determining the modulus of intact bovine vertebral cancellous bone tissue: Development and validation of a protocol

    NASA Astrophysics Data System (ADS)

    Engbretson, Andrew Craig

    Cancellous, or spongy, bone accounts for nearly 80% of the human skeleton's internal surface area, despite comprising only 20% of its mass. It is made up of a network of struts and plates that provide lightweight internal support to mammalian bones. In addition, it often serves as the main interface between the skeletal system and implanted devices such as artificial hips, knees, and fracture fixation devices. However, hip arthroplasties can succumb to loosening of the implant due to bone resorption, which is thought to be caused by a mismatch in both apparent and real stiffness between the device and the surrounding bone. Many studies have attempted to determine the Young's modulus of cancellous bone tissue, but the results are far from being in agreement. Reported values range from less than 1 to nearly 20 GPa. In addition, the small size of trabeculae has made dissection and testing a challenge. In this thesis, whole individual trabeculae from a bovine lumbar spine were tested in three-point bending to determine their Young's modulus using custom-made equipment to fit a miniature single-axis testing device. The device itself was validated by testing materials with moduli ranging from 1 to 200 GPa. The structure of the cancellous bone and the morphology of the individual struts were determined using micro x-ray computed tomography (muXCT). Individual struts were manually isolated from slices made using a low-speed saw under constant lubrication and measured under a stereomicroscope. Samples exhibiting no machined surfaces (and thus deemed to be whole, or "uncut" were compared to struts that had been cut by the saw during sectioning. Validation showed that the system was capable of determining the modulus of materials that were approximately five times stiffer than the expected cancellous modulus (copper, at 115 GPa) to within 10% of published values. This gave confidence in the results for bone. The modulus of the "uncut" specimens was found to be 15.28 2.26 GPa

  3. Prostate cancer specific integrin αvβ3 modulates bone metastatic growth and tissue remodeling

    PubMed Central

    McCabe, NP; De, S; Vasanji, A; Brainard, J; Byzova, TV

    2009-01-01

    The management of pain and morbidity owing to the spreading and growth of cancer within bone remains to be a paramount problem in clinical care. Cancer cells actively transform bone, however, the molecular requirements and mechanisms of this process remain unclear. This study shows that functional modulation of the αvβ3 integrin receptor in prostate cancer cells is required for progression within bone and determines tumor-induced bone tissue transformation. Using histology and quantitative microCT analysis, we show that αvβ3 integrin is required not only for tumor growth within the bone but for tumor-induced bone gain, a response resembling bone lesions in prostate cancer patients. Expression of normal, fully functional αvβ3 enabled tumor growth in bone (incidence: 4/4), whereas αvβ3 (—), inactive or constitutively active mutants of αvβ3 did not (incidence: 0/4, 0/6 and 1/7, respectively) within a 35-day-period. This response appeared to be bone-specific in comparison to the subcutis where tumor incidence was greater than 60% for all groups. Interestingly, bone residing prostate cancer cells expressing normal or dis-regulated αvβ3 (either inactive of constitutively active), but not those lacking β3 promoted bone gain or afforded protection from bone loss in the presence or absence of histologically detectable tumor 35 days following implantation. As bone is replete with ligands for β3 integrin, we next demonstrated that αvβ3 integrin activation on tumor cells is essential for the recognition of key bone-specific matrix proteins. As a result, prostate cancer cells expressing fully functional but not dis-regulated αvβ3 integrin are able to control their own adherence and migration to bone matrix, functions that facilitate tumor growth and control bone lesion development. PMID:17369840

  4. 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.

  5. Isotopic evidence for resorption of soft tissues and bone in immobilized dogs

    SciTech Connect

    Klein, L.; Player, J.S.; Heiple, K.G.; Bahniuk, E.; Goldberg, V.M.

    1982-02-01

    Various experimental methods for producing bone and ligament atrophy have yielded contradictory results. These methods include denervation, immobilization (both internal and external), and disarticulation. We studied a model of internal skeletal fixation for twelve weeks in dogs that were chronically prelabeled with 3H-tetracycline, 45Ca, and 3H-proline. Bone resorption was analyzed by the loss of 3H-tetracycline, and bone and soft-tissue mass were analyzed by the radiochemical and chemical analysis of calcium and collagen. The strength of the anterior cruciate ligament was studied in tension to failure when a fast rate of deformation was applied. Failure of the femur-ligament-tibia complex occurred through the insertion of the ligament into the tibia for both the experimental and the control limbs. Loss of collagen was greater in the tibia and femur than in the lateral meniscus and anterior cruciate ligament, and correlated with a mechanical failure via bone. No evidence for collagen replacement in atrophied tissues was found, but one-half of the resorbed calcium was conserved. The marked loss of 3H-tetracycline indicated that bone atrophy was the result of increased resorption of bone rather than decreased bone formation. Clinical Relevance: We have demonstrated significant atrophy of the soft tissues (lateral meniscus and anterior cruciate ligament) as well as of bone in immobilized joints of dogs. It is likely that the decrease in strength of the bone-ligament-bone complex is related to this atrophy of soft tissues and bone around the joint.

  6. The application of bone morphogenetic proteins to periodontal and peri-implant tissue regeneration: A literature review

    PubMed Central

    Sasikumar, Karuppanan P.; Elavarasu, Sugumari; Gadagi, Jayaprakash S.

    2012-01-01

    Progress in understanding the role of bone morphogenetic proteins (BMPs) in craniofacial and tooth development and the demonstration of stem cells in periodontal ligament have set the stage for periodontal regenerative therapy and tissue engineering. Furthermore, recent approval by the Food and Drug Administration of recombinant human BMPs for accelerating bone fusion in slow-healing fractures indicates that this protein family may prove useful in designing regenerative treatments in periodontics. In the near term, these advances are likely to be applied to periodontal surgery; ultimately, they may facilitate approaches to regenerating whole lost periodontal structures. PMID:23066304

  7. New Mechanism of Bone Cancer Pain: Tumor Tissue-Derived Endogenous Formaldehyde Induced Bone Cancer Pain via TRPV1 Activation.

    PubMed

    Wan, You

    2016-01-01

    In recent years, our serial investigations focused on the role of cancer cells-derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were upregulated by the local insulin-like growth factor I (IGF-I) produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation. PMID:26900062

  8. Carboxymethyl cellulose enables silk fibroin nanofibrous scaffold with enhanced biomimetic potential for bone tissue engineering application.

    PubMed

    Singh, B N; Panda, N N; Mund, R; Pramanik, K

    2016-10-20

    Novel silk fibroin (SF) and carboxymethyl cellulose (CMC) composite nanofibrous scaffold (SFC) were developed to investigate their ability to nucleate bioactive nanosized calcium phosphate (Ca/P) by biomineralization for bone tissue engineering application. The composite nanofibrous scaffold was prepared by free liquid surface electrospinning method. The developed composite nanofibrous scaffold was observed to control the size of Ca/P particle (≤100nm) as well as uniform nucleation of Ca/P over the surface. The obtained nanofibrous scaffolds were fully characterized for their functional, structural and mechanical property. The XRD and EDX analysis depicted the development of apatite like crystals over SFC scaffolds of nanospherical in morphology and distributed uniformly throughout the surface of scaffold. Additionally, hydrophilicity as a measure of contact angle and water uptake capacity is higher than pure SF scaffold representing the superior cell supporting property of the SF/CMC scaffold. The effect of biomimetic Ca/P on osteogenic differentiation of umbilical cord blood derived human mesenchymal stem cells (hMSCs) studied in early and late stage of differentiation shows the improved osteoblastic differentiation capability as compared to pure silk fibroin. The obtained result confirms the positive correlation of alkaline phosphatase activity, alizarin staining and expression of runt-related transcription factor 2, osteocalcin and type1 collagen representing the biomimetic property of the scaffolds. Thus, the developed composite has been demonstrated to be a potential scaffold for bone tissue engineering application. PMID:27474575

  9. Graphene and hydroxyapatite self-assemble into homogeneous, free standing nanocomposite hydrogels for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Xie, Xingyi; Hu, Kaiwen; Fang, Dongdong; Shang, Lihong; Tran, Simon D.; Cerruti, Marta

    2015-04-01

    Graphene-nanoparticle (NP) composites have shown potential in applications ranging from batteries to, more recently, tissue engineering. Graphene and NPs should be integrated into uniform free-standing structures for best results. However, to date, this has been achieved only in few examples; in most cases, graphene/NP powders lacking three-dimensional (3D) structure were produced. Here we report a facile and universal method that can be used to synthesize such structures based on colloidal chemistry. We start from aqueous suspensions of both graphene oxide nanosheets and citrate-stabilized hydroxyapatite (HA) NPs. Hydrothermal treatment of the mixtures of both suspensions reduces graphene oxide to graphene, and entraps colloidal HA NPs into the 3D graphene network thanks to a self-assembled graphite-like shell formed around it. Dialysis through this shell causes uniform NP deposition onto the graphene walls. The resulting graphene-HA gels are highly porous, strong, electrically conductive and biocompatible, making them promising scaffolds for bone tissue engineering. This method can be applied to produce a variety of free-standing 3D graphene-based nanocomposites with unprecedented homogeneity.Graphene-nanoparticle (NP) composites have shown potential in applications ranging from batteries to, more recently, tissue engineering. Graphene and NPs should be integrated into uniform free-standing structures for best results. However, to date, this has been achieved only in few examples; in most cases, graphene/NP powders lacking three-dimensional (3D) structure were produced. Here we report a facile and universal method that can be used to synthesize such structures based on colloidal chemistry. We start from aqueous suspensions of both graphene oxide nanosheets and citrate-stabilized hydroxyapatite (HA) NPs. Hydrothermal treatment of the mixtures of both suspensions reduces graphene oxide to graphene, and entraps colloidal HA NPs into the 3D graphene network thanks to

  10. Hierarchical Structure and Repair of Bone: Deformation, Remodelling, Healing

    NASA Astrophysics Data System (ADS)

    Fratzl, Peter; Weinkamer, Richard

    The design of natural materials follows a radically different paradigm as compared to engineering materials: organs are growing rather than being fabricated. As a main consequence, adaptation to changing conditions remains possible during the whole lifetime of a biological material. As a typical example of such a biological material, bone is constantly laid down by bone forming cells, osteoblasts, and removed by bone resorbing cells, osteoclasts. With this remodelling cycle of bone resorption and formation, the skeleton is able to adapt to changing needs at all levels of structural hierarchy. The hierarchical structure of bone is summarized in the second part of this chapter.

  11. Changes of cell-vascular complex in zones of adaptive remodeling of the bone tissue under microgravity conditions

    NASA Astrophysics Data System (ADS)

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

    2003-10-01

    We examined the peculiarities of the structure of the blood-vascular bed and perivascular cells in zones of osteogenesis in the epiphyses and metaphises of femoral bones of rats, flown aboard the US laboratory SLS-2 for two weeks by electron microscopy and histochemistry. In zones of bone remodeling, there was a tendency for a reduction of sinusoid capillary specific volume. Endotheliocytes preserve the typical structure. In the population of perivascular cells, we discovered differentiating osteogenic cells that contained alkaline phosphomonoesterase as well as cells that don't contain this enzyme and differentiate into fibroblasts. The fibroblasts genesis in zones of adaptive remodeling of spongy bones leads to a further development of fibrous tissue that is not subject to mineralization.

  12. 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. PMID:25969416

  13. A Three-Dimensional Scaffold-Based System for Modeling the Bone Marrow Tissue.

    PubMed

    Gheisari, Yousof; Vasei, Mohammad; Shafiee, Abbas; Soleimani, Masoud; Seyedjafari, Ehsan; Omidhkoda, Azadeh; Langroudi, Ladan; Ahmadbeigi, Naser

    2016-03-15

    Hematopoietic stem and progenitor cells (HPC) niche, consisting of HPC and their surrounding stromal components, is the fundamental unit for bone marrow (BM) tissue engineering. Previously, mouse BM-derived cell complexes with HPC niche unit properties called "niche-like units" were isolated and characterized. This study was aimed to evaluate the possibility of bioengineering marrow tissue in heterotypic sites using niche-like units in combination with three-dimensional scaffolds. BM niche-like units were isolated from GFP-transgenic C57BL/6 mice and seeded on electrospun poly (L-lactide) nanofiber scaffolds, which were then roll-folded and aseptically implanted into the peritoneal cavity of irradiated wild-type mice. One month after implantation, donor-derived cells were detected in peripheral blood of the recipients and contributed to restoration of all blood lineages. The transplanted bioengineered tissue histologically resembled native BM structure and was connected to the mouse systemic circulation. Long-term self-renewal was confirmed by serial transplantation into tertiary recipients. In conclusion, this study establishes a novel system for BM tissue engineering, which can be used to improve the HPC transplantation outcomes especially in cases where HPC niche is damaged and also as an in vivo model to test the effects of different factors on hematopoiesis. PMID:26763629

  14. Cytokine Combination Therapy Prediction for Bone Remodeling in Tissue Engineering Based on the Intracellular Signaling Pathway

    PubMed Central

    Sun, Xiaoqiang; Su, Jing; Bao, Jiguang; Peng, Tao; Zhang, Le; Zhang, Yuanyuan; Yang, Yunzhi; Zhou, Xiaobo

    2012-01-01

    The long-term performance of tissue-engineered bone grafts is determined by a dynamic balance between bone regeneration and resorption. We proposed using embedded cytokine slow-releasing hydrogels to tune this balance toward a desirable final bone density. In this study we established a systems biology model, and quantitatively explored the combinatorial effects of delivered cytokines from hydrogels on final bone density. We hypothesized that: 1) bone regeneration was driven by transcription factors Runx2 and Osterix, which responded to released cytokines, such as Wnt, BMP2, and TGFβ, drove the development of osteoblast lineage, and contributed to bone mass generation; and 2) the osteoclast lineage, on the other hand, governed the bone resorption, and communications between these two lineages determined the dynamics of bone remodeling. In our model, Intracellular signaling pathways were represented by ordinary differential equations, while the intercellular communications and cellular population dynamics were modeled by stochastic differential equations. Effects of synergistic cytokine combinations were evaluated by Loewe index and Bliss index. Simulation results revealed that the Wnt/BMP2 combinations released from hydrogels showed best control of bone regeneration and synergistic effects, and suggested optimal dose ratios of given cytokine combinations released from hydrogels to most efficiently control the long-term bone remodeling. We revealed the characteristics of cytokine combinations of Wnt/BMP2 which could be used to guide the design of in vivo bone scaffolds and the clinical treatment of some diseases such as osteoporosis. PMID:22910219

  15. The Effect of Osteoporosis Treatments on Fatigue Properties of Cortical Bone Tissue

    PubMed Central

    Brock, Garry R.; Chen, Julia T.; Ingraffea, Anthony R.; MacLeay, Jennifer; Pluhar, G. Elizabeth; Boskey, Adele L.; van der Meulen, Marjolein C.H.

    2015-01-01

    Bisphosphonates are commonly prescribed for treatment of osteoporosis. Long-term use of bisphosphonates has been correlated to atypical femoral fractures (AFF). AFFs arise from fatigue damage to bone tissue that cannot be repaired due to pharmacologic treatments. Despite fatigue being the primary damage mechanism of AFFs, the effects of osteoporosis treatments on fatigue properties of cortical bone are unknown. To examine if fatigue-life differences occur in bone tissue after different pharmacologic treatments for osteoporosis, we tested bone tissue from the femurs of sheep given a metabolic acidosis diet to induce osteoporosis, followed by treatment with a selective estrogen reception modulator (raloxifene), a bisphosphonate (alendronate or zoledronate), or parathyroid hormone (teriparatide, PTH). Beams of cortical bone tissue were created and tested in four-point bending fatigue to failure. Tissues treated with alendronate had reduced fatigue life and less modulus loss at failure compared to other treatments, while tissue treated with PTH had a prolonged fatigue life. No loss of fatigue life occurred with zoledronate treatment despite its greater binding affinity and potency compared to alendronate. Tissue mineralization measured by microCT did not explain the differences seen in fatigue behavior. Increased fatigue life with PTH suggests that current treatment methods for AFF could have beneficial effects for restoring fatigue life. These results indicate that fatigue life differs with each type of osteoporosis treatment. PMID:25642445

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

    PubMed Central

    Kaempfen, Alexandre; Todorov, Atanas; Güven, Sinan; Largo, René D.; Jaquiéry, Claude; Scherberich, Arnaud; Martin, Ivan; Schaefer, Dirk J.

    2015-01-01

    The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step) or only after six weeks of subcutaneous “incubation” (2-step). After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed. PMID:26053395

  17. Structure of the tendon connective tissue.

    PubMed

    Kannus, P

    2000-12-01

    Tendons consist of collagen (mostly type I collagen) and elastin embedded in a proteoglycan-water matrix with collagen accounting for 65-80% and elastin approximately 1-2% of the dry mass of the tendon. These elements are produced by tenoblasts and tenocytes, which are the elongated fibroblasts and fibrocytes that lie between the collagen fibers, and are organized in a complex hierarchical scheme to form the tendon proper. Soluble tropocollagen molecules form cross-links to create insoluble collagen molecules which then aggregate progressively into microfibrils and then into electronmicroscopically clearly visible units, the collagen fibrils. A bunch of collagen fibrils forms a collagen fiber, which is the basic unit of a tendon. A fine sheath of connective tissue called endotenon invests each collagen fiber and binds fibers together. A bunch of collagen fibers forms a primary fiber bundle, and a group of primary fiber bundles forms a secondary fiber bundle. A group of secondary fiber bundles, in turn, forms a tertiary bundle, and the tertiary bundles make up the tendon. The entire tendon is surrounded by a fine connective tissue sheath called epitenon. The three-dimensional ultrastructure of tendon fibers and fiber bundles is complex. Within one collagen fiber, the fibrils are oriented not only longitudinally but also transversely and horizontally. The longitudinal fibers do not run only parallel but also cross each other, forming spirals. Some of the individual fibrils and fibril groups form spiral-type plaits. The basic function of the tendon is to transmit the force created by the muscle to the bone, and, in this way, make joint movement possible. The complex macro- and microstructure of tendons and tendon fibers make this possible. During various phases of movements, the tendons are exposed not only to longitudinal but also to transversal and rotational forces. In addition, they must be prepared to withstand direct contusions and pressures. The above

  18. 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

  19. 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

  20. Nano-hydroxyapatite composite biomaterials for bone tissue engineering--a review.

    PubMed

    Venkatesan, Jayachandran; Kim, Se-Kwon

    2014-10-01

    In recent years, significant development has been achieved in the construction of artificial bone with ceramics, polymers and metals. Nano-hydroxyapatite (nHA) is widely used bioceramic material for bone graft substitute owing to its biocompatibility and osteoconductive properties. nHA with chitin, chitosan, collagen, gelatin, fibrin, polylactic acid, polycaprolactone, poly(lactic-co-glycolic) acid, polyamide, polyvinyl alcohol, polyurethane and polyhydroxybutyrate based composite scaffolds have been explored in the present review for bone graft substitute. This article further reviews the preparative methods, chemical interaction, biocompatibiity, biodegradation, alkaline phosphatase activity, mineralization effect, mechanical properties and delivery of nHA-based nanocomposites for bone tissue regeneration. The nHA based composite biomaterials proved to be promising biomaterials for bone tissue engineering. PMID:25992432

  1. Crosslinked pullulan/cellulose acetate fibrous scaffolds for bone tissue engineering.

    PubMed

    Atila, Deniz; Keskin, Dilek; Tezcaner, Ayşen

    2016-12-01

    Natural polymer based fibrous scaffolds have been explored for bone tissue engineering applications; however, their inadequate 3-dimensionality and poor mechanical properties are among the concerns for their use as bone substitutes. In this study, pullulan (P) and cellulose acetate (CA), two polysaccharides, were electrospun at various P/CA ratios (P80/CA20, P50/CA50, and P20/CA80%) to develop 3D fibrous network. The scaffolds were then crosslinked with trisodium trimetaphosphate (STMP) to improve the mechanical properties and to delay fast weight loss. The lowest weight loss was observed for the groups that were crosslinked with P/STMP 2/1 for 10min. Fiber morphologies of P50/CA50 were more uniform without phase separation and this group was crosslinked most efficiently among groups. It was found that mechanical properties of P20/CA80 and P50/CA50 were higher than that of P80/CA20. After crosslinking strain values of P50/CA50 scaffolds were improved and these scaffolds became more stable. Unlike P80/CA20, uncrosslinked P50/CA50 and P20/CA80 were not lost in PBS. Among all groups, crosslinked P50/CA50 scaffolds had more uniform pores; therefore this group was used for bioactivity and cell culture studies. Apatite-like structures were observed on fibers after SBF incubation. Human Osteogenic Sarcoma Cell Line (Saos-2) seeded onto crosslinked P50/CA50 scaffolds adhered and proliferated. The functionality of cells was tested by measuring ALP activity of the cells and the results indicated their osteoblastic differentiation. In vitro tests showed that scaffolds were cytocompatible. To sum up, crosslinked P50/CA50 scaffolds were proposed as candidate cell carriers for bone tissue engineering applications. PMID:27612808

  2. Mechanical microenvironments and protein expression associated with formation of different skeletal tissues during bone healing.

    PubMed

    Miller, Gregory J; Gerstenfeld, Louis C; Morgan, Elise F

    2015-11-01

    Uncovering the mechanisms of the sensitivity of bone healing to mechanical factors is critical for understanding the basic biology and mechanobiology of the skeleton, as well as for enhancing clinical treatment of bone injuries. This study refined an experimental method of measuring the strain microenvironment at the site of a bone injury during bone healing. This method used a rat model in which a well-controlled bending motion was applied to an osteotomy to induce the formation of pseudarthrosis that is composed of a range of skeletal tissues, including woven bone, cartilage, fibrocartilage, fibrous tissue, and clot tissue. The goal of this study was to identify both the features of the strain microenvironment associated with formation of these different tissues and the expression of proteins frequently implicated in sensing and transducing mechanical cues. By pairing the strain measurements with histological analyses that identified the regions in which each tissue type formed, we found that formation of the different tissue types occurs in distinct strain microenvironments and that the type of tissue formed is correlated most strongly to the local magnitudes of extensional and shear strains. Weaker correlations were found for dilatation. Immunohistochemical analyses of focal adhesion kinase and rho family proteins RhoA and CDC42 revealed differences within the cartilaginous tissues in the calluses from the pseudarthrosis model as compared to fracture calluses undergoing normal endochondral bone repair. These findings suggest the involvement of these proteins in the way by which mechanical stimuli modulate the process of cartilage formation during bone healing. PMID:25822264

  3. Bone Marrow Leptin Signaling Mediates Obesity-Associated Adipose Tissue Inflammation in Male Mice

    PubMed Central

    Dib, Lea H.; Ortega, M. Teresa; Fleming, Sherry D.; Melgarejo, Tonatiuh

    2014-01-01

    Obesity is characterized by an increased recruitment of proinflammatory macrophages to the adipose tissue (AT), leading to systemic inflammation and metabolic disease. The pathogenesis of this AT inflammation, however, remains to be elucidated. The circulating adipokine leptin is increased in obesity and is involved in immune cell function and activation. In the present study, we investigated the role of leptin in the induction of obesity-associated inflammation. We generated radiation chimeric C57BL/6J mice reconstituted with either leptin receptor-deficient (db/db) or wild-type (WT) bone marrow and challenged them with a high-fat diet (HFD) for 16 weeks. Mice reconstituted with db/db bone marrow (WT/db), had significantly lower body weight and adiposity compared with mice with WT bone marrow (WT/WT). Gonadal AT in WT/db mice displayed a 2-fold lower expression of the inflammatory genes Tnfa, Il6, and Ccl2. In addition, gonadal fat of WT/db mice contained significantly fewer crown-like structures compared with WT/WT mice, and most of their AT macrophages expressed macrophage galactose-type C type lectin 1 (MGL1) and were C-C chemokine receptor type 2 (CCR2)-negative, indicative of an anti-inflammatory phenotype. Moreover, WT/db mice exhibited greater insulin sensitivity compared with WT/WT mice. These data show that disrupted leptin signaling in bone marrow-derived cells attenuates the proinflammatory conditions that mediate many of the metabolic complications that characterize obesity. Our findings establish a novel mechanism involved in the regulation of obesity-associated systemic inflammation and support the hypothesis that leptin is a proinflammatory cytokine. PMID:24169547

  4. Use of a biological reactor and platelet-rich plasma for the construction of tissue-engineered bone to repair articular cartilage defects

    PubMed Central

    Li, Huibo; Sun, Shui; Liu, Haili; Chen, Hua; Rong, Xin; Lou, Jigang; Yang, Yunbei; Yang, Yi; Liu, Hao

    2016-01-01

    Articular cartilage defects are a major clinical burden worldwide. Current methods to repair bone defects include bone autografts, allografts and external fixation. In recent years, the repair of bone defects by tissue engineering has emerged as a promising approach. The present study aimed to assess a novel method using a biological reactor with platelet-rich plasma to construct tissue-engineered bone. Beagle bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into osteoblasts and chondroblasts using platelet-rich plasma and tricalcium phosphate scaffolds cultured in a bioreactor for 3 weeks. The cell scaffold composites were examined by scanning electron microscopy (SEM) and implanted into beagles with articular cartilage defects. The expression of osteogenic markers, alkaline phosphatase and bone γ-carboxyglutamate protein (BGLAP) were assessed using polymerase chain reaction after 3 months. Articular cartilage specimens were observed histologically. Adhesion and distribution of BMSCs on the β-tricalcium phosphate (β-TCP) scaffold were confirmed by SEM. Histological examination revealed that in vivo bone defects were largely repaired 12 weeks following implantation. The expression levels of alkaline phosphatase (ALP) and BGLAP in the experimental groups were significantly elevated compared with the negative controls. BMSCs may be optimum seed cells for tissue engineering in bone repair. Platelet-rich plasma (PRP) provides a rich source of cytokines to promote BMSC function. The β-TCP scaffold is advantageous for tissue engineering due to its biocompatibility and 3D structure that promotes cell adhesion, growth and differentiation. The tissue-engineered bone was constructed in a bioreactor using BMSCs, β-TCP scaffolds and PRP and displayed appropriate morphology and biological function. The present study provides an efficient method for the generation of tissue-engineered bone for cartilage repair, compared with previously used

  5. Fabrication of Biomimetic Bone Tissue Using Mesenchymal Stem Cell-Derived Three-Dimensional Constructs Incorporating Endothelial Cells

    PubMed Central

    Sasaki, Jun-Ichi; Hashimoto, Masanori; Yamaguchi, Satoshi; Itoh, Yoshihiro; Yoshimoto, Itsumi; Matsumoto, Takuya; Imazato, Satoshi

    2015-01-01

    The development of technologies to promote vascularization of engineered tissue would drive major developments in tissue engineering and regenerative medicine. Recently, we succeeded in fabricating three-dimensional (3D) cell constructs composed of mesenchymal stem cells (MSCs). However, the majority of cells within the constructs underwent necrosis due to a lack of nutrients and oxygen. We hypothesized that incorporation of vascular endothelial cells would improve the cell survival rate and aid in the fabrication of biomimetic bone tissues in vitro. The purpose of this study was to assess the impact of endothelial cells combined with the MSC constructs (MSC/HUVEC constructs) during short- and long-term culture. When human umbilical vein endothelial cells (HUVECs) were incorporated into the cell constructs, cell viability and growth factor production were increased after 7 days. Furthermore, HUVECs were observed to proliferate and self-organize into reticulate porous structures by interacting with the MSCs. After long-term culture, MSC/HUVEC constructs formed abundant mineralized matrices compared with those composed of MSCs alone. Transmission electron microscopy and qualitative analysis revealed that the mineralized matrices comprised porous cancellous bone-like tissues. These results demonstrate that highly biomimetic bone tissue can be fabricated in vitro by 3D MSC constructs incorporated with HUVECs. PMID:26047122

  6. Controlled nucleation of hydroxyapatite on alginate scaffolds for stem cell-based bone tissue engineering

    PubMed Central

    Suárez-González, Darilis; Barnhart, Kara; Saito, Eiji; Vanderby, Ray; Hollister, Scott; Murphy, William L.

    2010-01-01

    Current bone tissue engineering strategies aim to grow a tissue similar to native bone by combining cells and biologically active molecules with a scaffold material. In this study, a macroporous scaffold made from the seaweed-derived polymer alginate was synthesized and mineralized for cell-based bone tissue engineering applications. Nucleation of a bone-like hydroxyapatite mineral was achieved by incubating the scaffold in modified simulated body fluids (mSBF) for four weeks. Analysis using scanning electron microscopy and energy dispersive x-ray analysis indicated growth of a continuous layer of mineral primarily composed of calcium and phosphorous. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue. In addition to the mineral characterization, the ability to control nucleation on the surface, into the bulk of the material, or on the inner pore surfaces of scaffolds was demonstrated. Finally, human MSCs attached and proliferated on the mineralized scaffolds and cell attachment improved when seeding cells on mineral coated alginate scaffolds. This novel alginate- HAP composite material could be used in bone tissue engineering as a scaffold material to deliver cells, and perhaps also biologically active molecules. PMID:20574984

  7. Molecular characterization of Treponema denticola infection-induced bone and soft tissue transcriptional profiles

    PubMed Central

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

    2010-01-01

    SUMMARY Treponema denticola is associated with subgingival biofilms in adult periodontitis and with acute necrotizing ulcerative gingivitis. However, the molecular mechanisms by which T. denticola impacts periodontal inflammation and alveolar bone resorption remain unclear. Here, we examined changes in the host transcriptional profiles during a T. denticola infection using a murine calvarial model of inflammation and bone resorption. T. denticola was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and the calvarial bones were excised. RNA was isolated and analysed for transcript profiling using Murine GeneChip® arrays. Following T. denticola infection, 2905 and 1234 genes in the infected calvarial bones and soft tissues, respectively, were differentially expressed (p ≤ 0.05). Biological pathways significantly impacted by T. denticola infection in calvarial bone and calvarial tissue included leukocyte transendothelial migration, cell adhesion (immune system) molecules, cell cycle, extracellular matrix–receptor interaction, focal adhesion, B-cell receptor signaling and transforming growth factor-β signaling pathways resulting in proinflammatory, chemotactic effects, and T-cell stimulation. In conclusion, localized T. denticola infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed calvarial bone and soft tissues. PMID:20618700

  8. 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. PMID:15701371

  9. Local Mechanical Stimuli Regulate Bone Formation and Resorption in Mice at the Tissue Level

    PubMed Central

    Schulte, Friederike A.; Ruffoni, Davide; Lambers, Floor M.; Christen, David; Webster, Duncan J.; Kuhn, Gisela; Müller, Ralph

    2013-01-01

    Bone is able to react to changing mechanical demands by adapting its internal microstructure through bone forming and resorbing cells. This process is called bone modeling and remodeling. It is evident that changes in mechanical demands at the organ level must be interpreted at the tissue level where bone (re)modeling takes place. Although assumed for a long time, the relationship between the locations of bone formation and resorption and the local mechanical environment is still under debate. The lack of suitable imaging modalities for measuring bone formation and resorption in vivo has made it difficult to assess the mechanoregulation of bone three-dimensionally by experiment. Using in vivo micro-computed tomography and high resolution finite element analysis in living mice, we show that bone formation most likely occurs at sites of high local mechanical strain (p<0.0001) and resorption at sites of low local mechanical strain (p<0.0001). Furthermore, the probability of bone resorption decreases exponentially with increasing mechanical stimulus (R2 = 0.99) whereas the probability of bone formation follows an exponential growth function to a maximum value (R2 = 0.99). Moreover, resorption is more strictly controlled than formation in loaded animals, and ovariectomy increases the amount of non-targeted resorption. Our experimental assessment of mechanoregulation at the tissue level does not show any evidence of a lazy zone and suggests that around 80% of all (re)modeling can be linked to the mechanical micro-environment. These findings disclose how mechanical stimuli at the tissue level contribute to the regulation of bone adaptation at the organ level. PMID:23637993

  10. Chemodectomas arising in temporal bone structures

    SciTech Connect

    Dickens, W.J.; Million, R.R.; Cassisi, N.J.; Singleton, G.T.

    1982-02-01

    Eighteen patients with chemodectomas arising in temporal bone structures were evaluated and treated at the University of Florida. Seventeen patients have each been followed a minimum of 3 years. Patients were retrospectively staged as having ''local'' or ''advanced'' disease, depending on the presence or absence of bone destruction and/or cranial nerve involvement. Fourteen of the patients received radiation therapy as all or part of their therapy; 6 patients were treated with radiation therapy alone, 3 patients were irradiated immediately postoperatively for residual disease, and 5 patients had radiation therapy for recurrence after operation. They were treated with cobalt-60 radiation with doses ranging from 3760 to 5640 rad. All irradiated patients demonstrated evidence of tumor regression, and none have had tumor recurrence with followup of 3-12 years. Of the 8 patients with cranial nerve paralysis prior to therapy, 5 had return of function of 1 or more cranial nerves. One of 6 patients treated initially with radiation therapy had a complication, while 6 of 8 patients irradiated postoperatively had complications. None of the complications were fatal. Three patients treated by operation for early disease limited to the hypotympanum had the disease controlled for 11-12 years. Guidelines for the selection of initial therapy are discussed.

  11. Bone Grafts

    MedlinePlus

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

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

    PubMed Central

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

    2012-01-01

    Reconstruction of large bone defects remains problematic in orthopedic and craniofacial clinical practice. Autografts are limited in supply and are associated with donor site morbidity while other materials show poor integration with the host’s own bone. This lack of integration is often due to the absence of periosteum, the outer layer of bone that contains osteoprogenitor cells and is critical for the growth and remodeling of bone tissue. In this study we developed a one-step platform to electrospin nanofibrous scaffolds from chitosan, which also contain hydroxyapatite nanoparticles and are crosslinked with genipin. We hypothesized that the resulting composite scaffolds represent a microenvironment that emulates the physical, mineralized structure and mechanical properties of non-weight bearing bone extracellular matrix while promoting osteoblast differentiation and maturation similar to the periosteum. The ultrastructure and physicochemical properties of the scaffolds were studied using scanning electron microscopy and spectroscopic techniques. The average fiber diameters of the electrospun scaffolds were 227±154 nm as spun, and increased to 335±119 nm after crosslinking with genipin. Analysis by X-ray diffraction, Fourier transformed infrared spectroscopy and energy dispersive spectroscopy confirmed the presence of characteristic features of hydroxyapatite in the composite chitosan fibers. The Young’s modulus of the composite fibrous scaffolds was 142±13 MPa, which is similar to that of the natural periosteum. Both pure chitosan scaffolds and composite hydroxyapatite-containing chitosan scaffolds supported adhesion, proliferation and osteogenic differentiation of mouse 7F2 osteoblast-like cells. Expression and enzymatic activity of alkaline phosphatase, an early osteogenic marker, were higher in cells cultured on the composite scaffolds as compared to pure chitosan scaffolds, reaching a significant, 2.4 fold, difference by day 14 (p<0.05). Similarly

  13. 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.

  14. Soft Tissue Swelling Associated with the Use of Recombinant Human Bone Morphogenetic Protein-2 in Long Bone Non-unions

    PubMed Central

    Young, Andrew; Mirarchi, Adam

    2015-01-01

    Introduction: This report describes two cases of long bone non-union associated with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) and is the first of its kind. The first case describes a 25-year-old male who sustained a left diaphyseal femoral shaft fracture initially treated with operative fixation using an intramedullary nail, which subsequently loosened distally and was treated with exchange nailing and rhBMP-2 application. This patient developed acute local soft tissue inflammation post-operatively. The second case describes a 61-year-old female who sustained a right diaphyseal humeral shaft fracture that was initially treated with intramedullary nail fixation with subsequent distal interlock screw loosening. She underwent nail removal, and compression plating with rhBMP-2 placement, and postoperatively developed severe acute local tissue swelling centered over the rhBMP-2 sponge. Surgeons should be aware that rhBMP-2 may cause local acute tissue swelling and recombinant bone morphogenic proteins such as rhBMP-2 may have a role in the management for atrophic fracture non-unions. The authors recommend careful consideration prior to rhBMP-2 use in long bone non-unions. PMID:27299059

  15. Bone tissue induction, using a COLLOSS-filled titanium fibre mesh-scaffolding material.

    PubMed

    Walboomers, X Frank; Jansen, John A

    2005-08-01

    Scaffold materials for bone tissue engineering often are supplemented with bone morphogenetic proteins (BMPs). In the current study we aimed to investigate COLLOSS, a bovine extracellular matrix product containing native BMPs. Hollow cylindrical implants were made, with a length of 10 mm, a 3 mm inner diameter, and a 5 mm outer diameter, from titanium fibre mesh. The central space of the tube was filled with 20 mg COLLOSS. Subsequently, these implants, as well as non-loaded controls, were implanted subcutaneously into the back of Wistar rats, with n=6 for all study groups. After implantation periods of 2, 8, and 12 weeks, tissue-covered implants were retrieved, and sections were made, perpendicular to the long axis of the tube. Histology showed, that all implants were surrounded by a thin fibrous tissue capsule. After 2 weeks of implantation, the COLLOSS material was reduced in size inside the loaded implants, but no bone-like tissue formation was evident. After 8 weeks, in two out of six loaded specimens, new-formed bone- and bone marrow-like tissues could be observed. After 12 weeks, this had increased to five out of six COLLOSS-loaded samples. The amount of bone-like tissue did not differ between 8 and 12 weeks, and on average occupied 15% of the central space of the tube. In the non-loaded control samples, only connective tissue ingrowth was observed. In conclusion, we can say that COLLOSS material loaded in a titanium fibre mesh tube, showed bone-inducing properties. The final efficacy of these osteo-inductive properties has to be confirmed in future large animal studies. PMID:15763257

  16. A novel squid pen chitosan/hydroxyapatite/β-tricalcium phosphate composite for bone tissue engineering.

    PubMed

    Shavandi, Amin; Bekhit, Alaa El-Din A; Sun, Zhifa; Ali, Azam; Gould, Maree

    2015-10-01

    Squid pen chitosan was used in the fabrication of biocomposite scaffolds for bone tissue engineering. Hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) obtained from waste mussel shells were used as the calcium phosphate source. The composite was prepared using 2.5% tripolyphosphate (TPP) and 1% glycerol as a cross-linker and plasticizer, respectively. The weight percent (wt.%) ratios of the ceramic components in the composite were 20/10/70, 30/20/50 and 40/30/30 (HA/β-TCP/Chi). The biodegradation rate and structural properties of the scaffolds were investigated. Scanning electron microscopy (SEM) and microCT(μCT) results indicated that the composites have a well defined lamellar structure with an average pore size of 200 μm. The porosity of the composites decreased from 88 to 56% by increasing the ratio of HA/β-TCP from 30 to 70%. After 28 days of incubation in a physiological solution, the scaffolds were degraded by approximately 30%. In vitro investigations showed that the composites were cytocompatible and supported the growth of L929 and Saos-2 cells. The obtained data suggests that the squid pen chitosan composites are potential candidates for bone regeneration. PMID:26117768

  17. Bone tissue phantoms for optical flowmeters at large interoptode spacing generated by 3D-stereolithography

    PubMed Central

    Binzoni, Tiziano; Torricelli, Alessandro; Giust, Remo; Sanguinetti, Bruno; Bernhard, Paul; Spinelli, Lorenzo

    2014-01-01

    A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption coefficient, reduced scattering coefficient and refractive index of the optical phantom have been measured to ensure that the optical parameters reasonably reproduce real human bone tissue in vivo. An experimental demonstration of a possible use of the optical phantom, utilizing a laser-Doppler flowmeter, is also presented. PMID:25136496

  18. Thermoplastic starch/ethylene vinyl alcohol/forsterite nanocomposite as a candidate material for bone tissue engineering.

    PubMed

    Mahdieh, Zahra; Bagheri, Reza; Eslami, Masoud; Amiri, Mohammad; Shokrgozar, Mohammad Ali; Mehrjoo, Morteza

    2016-12-01

    Recently, biodegradable polymers such as starch based blends have been well renowned in the biomedical field. Studies have considered them suitable for bone scaffolds, bone cements, tissue engineering scaffolds, drug delivery systems and hydrogels. The aim of this study was to synthesize nanocomposite biomaterial consisting a blend of thermoplastic starch and ethylene vinyl alcohol as the polymer matrix, and nano-structured forsterite as the ceramic reinforcing phase for bone tissue engineering applications. Furthermore, vitamin E was applied as a thermal stabilizer during melt compounding. Extrusion and injection molding were incorporated for melt blending and shaping of samples, respectively. With blending thermoplastic starch and ethylene vinyl alcohol, some properties of thermoplastic starch such as degradation rate and water absorption were modified. In addition, using nanoforsterite as the ceramic reinforcing phase resulted in the improvement of mechanical and biological traits. The addition of nanoforsterite decreased the weight loss of the thermoplastic starch and ethylene vinyl alcohol blend in simulated body fluid. Moreover, this addition modified the pH in the MTT (methyl thiazolyl tetrazolium) assay and stimulated the cell proliferation. Cell adhesion assays indicated a favorable interaction between cells and the biomaterial. The proposed nanocomposite has appropriate biocompatibility, as well as mechanical properties in order to be used in bone tissue engineering. PMID:27612717

  19. Correlation of Subchondral Bone Density and Structure from Plain Radiographs with Micro Computed Tomography Ex Vivo.

    PubMed

    Hirvasniemi, Jukka; Thevenot, Jérôme; Kokkonen, Harri T; Finnilä, Mikko A; Venäläinen, Mikko S; Jämsä, Timo; Korhonen, Rami K; Töyräs, Juha; Saarakkala, Simo

    2016-05-01

    Osteoarthritis causes changes in the subchondral bone structure and composition. Plain radiography is a cheap, fast, and widely available imaging method. Bone tissue can be well seen from plain radiograph, which however is only a 2D projection of the actual 3D structure. Therefore, the aim was to investigate the relationship between bone density- and structure-related parameters from 2D plain radiograph and 3D bone parameters assessed from micro computed tomography (µCT) ex vivo. Right tibiae from eleven cadavers without any diagnosed joint disease were imaged using radiography and with µCT. Bone density- and structure-related parameters were calculated from four different locations from the radiographs of proximal tibia and compared with the volumetric bone microarchitecture from the corresponding regions. Bone density from the plain radiograph was significantly related with the bone volume fraction (r = 0.86; n = 44; p < 0.01). Mean homogeneity index for orientation of local binary patterns (HIangle,mean) and fractal dimension of vertical structures (FDVer) were related (p < 0.01) with connectivity density (HIangle,mean: r = -0.73, FDVer: r = 0.69) and trabecular separation (HIangle,mean: r = 0.73, FDVer: r = -0.70) when all ROIs were pooled together (n = 44). Bone density and structure in tibia from standard clinically available 2D radiographs are significantly correlated with true 3D microstructure of bone. PMID:26369637

  20. FT-IR Imaging of Native and Tissue-Engineered Bone and Cartilage

    PubMed Central

    Boskey, Adele; Camacho, Nancy Pleshko

    2007-01-01

    Fourier transform Infrared (FT-IR) imaging and microspectroscopy have been extensively applied to the analyses of tissues in health and disease. Spatially resolved mid-infrared data has provided insights into molecular changes that occur in diseases of connective or collagen-based tissues, including osteoarthritis, osteoporosis, osteogenesis imperfecta, osteopetrosis and pathologic calcifications. These techniques have also been used to probe chemical changes associated with load, disuse, and micro-damage in bone, and with degradation and repair in cartilage. This review summarizes the applications of FT-IR microscopy and imaging for analyses of bone and cartilage in healthy and diseased tissues, and illustrates the application of these techniques for the characterization of tissue engineered bone and cartilage. PMID:17175021

  1. 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. PMID:26415888

  2. Model of the distraction callus tissue behavior during bone transport based in experiments in vivo.

    PubMed

    Mora-Macías, Juan; Reina-Romo, Esther; Domínguez, Jaime

    2016-08-01

    Bone transport studies have measured the forces related to bone segment distraction (Brunner et al., 1994; Hyodo et al., 1996). However, no distraction force distribution between callus and docking-site was reported. Besides, most of these works have not provided continuous and long-term force relaxation measurements. The fit of the relaxation curves allows for modeling the mechanical behavior of the callus tissue during distraction osteogenesis, particularly in bone transport, where the resistance of the soft tissue and muscle is reduced compared with the bone lengthening. Bone transport experiments were carried out in sheep in which the distraction force was monitored continuously in vivo. The daily force relaxation curves were fitted, and two experimental models of the mechanical behavior of the callus tissue were obtained, assuming the total daily force relaxation or the accumulation of the residual forces. According to these models, the residual force 24h after each distraction step was a maximum of 71.6N, and the peak distraction force increased with the number of steps from 7-34N to 41-246N. The maximum residual force values that were predicted are much lower than those measured during bone lengthening in the literature. These results indirectly differentiate the influence of the surrounding soft tissues during bone transport compared with bone lengthening. Moreover, experimental measurements showed that distraction force through the docking-site was negligible with respect to distraction force through the callus. Experimental models of the callus tissue allow for an understanding of the mechanobiology of distraction osteogenesis and for predicting outcomes in its application processes. PMID:27111628

  3. Peptide-incorporated 3D porous alginate scaffolds with enhanced osteogenesis for bone tissue engineering.

    PubMed

    Luo, Zuyuan; Yang, Yue; Deng, Yi; Sun, Yuhua; Yang, Hongtao; Wei, Shicheng

    2016-07-01

    Good bioactivity and osteogenesis of three-dimensional porous alginate scaffolds (PAS) are critical for bone tissue engineering. In this work, alginate and bone-forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7 (BMP-7), have been combined together (without carbodiimide chemistry treatment) to develop peptide-incorporated PAS (p-PAS) for promoting bone repairing ability. The mechanical properties and SEM images show no difference between pure PAS and p-PAS. The release kinetics of the labeled peptide with 6-carboxy tetramethyl rhodamine from the PAS matrix suggests that the peptide is released in a relatively sustained manner. In the cell experiment, p-PAS show higher cell adhesion, spreading, proliferation and alkaline phosphatase (ALP) activity than the pristine PAS group, indicating that the BFP-1 released from p-PAS could significantly promote the aggregation and differentiation of osteoblasts, especially at 10μg/mL of trapped peptide concentration (p-PAS-10). Furthermore, p-PAS-10 was implanted into Beagle calvarial defects and bone regeneration was analyzed after 4 weeks. New bone formation was assessed by calcein and Masson's trichrome staining. The data reveal that p-PAS group exhibits significantly enhanced oseto-regenerative capability in vivo. The peptide-modified PAS with promoted bioactivity and osteogenic differentiation in vitro as well as bone formation ability in vivo could be promising tissue engineering materials for repairing and regeneration of bone defects. PMID:27022863

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

    SciTech Connect

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

    2013-02-05

    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 SiO{sub 2} 70 mol%, CaO 26 mol % and P{sub 2}O{sub 5} 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.

  5. Cross-correlative 3D micro-structural investigation of human bone processed into bone allografts.

    PubMed

    Singh, Atul Kumar; Gajiwala, Astrid Lobo; Rai, Ratan Kumar; Khan, Mohd Parvez; Singh, Chandan; Barbhuyan, Tarun; Vijayalakshmi, S; Chattopadhyay, Naibedya; Sinha, Neeraj; Kumar, Ashutosh; Bellare, Jayesh R

    2016-05-01

    Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all

  6. Variation of flow-induced stresses within scaffolds used in bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Papavassiliou, Dimitrios; Pham, Ngoc; Voronov, Roman; Sikavitsas, Vassilios

    2011-11-01

    Bone tissue engineering is often based on seeding adult stem cells on porous scaffolds and subsequently placing these scaffolds in flow perfusion bioreactors to stimulate cell differentiation and cell growth. In the present study, the distribution of stresses in structured porous scaffolds under flow is investigated by calculating the probability density function of flow-induced stresses in different scaffold geometries with simulations. The physical reason for the development of particular stress distributions is further explored, and it is found that the direction of flow relative to the internal architecture of the porous scaffold is important for stress distributions. When the flow direction is random relative to the configuration of the geometric elements making up the scaffold, it is found that a common distribution, such as the one suggested by Voronov et al. (Appl. Phys. Let., 2010, 97:024101), can be used to describe the stress distribution. NSF CBET-070081.

  7. Lysineurethanedimethacrylate--a novel generation of amino acid based monomers for bone cements and tissue repair.

    PubMed

    Müh, Ekkehard; Zimmermann, Jörg; Kneser, Ulrich; Marquardt, Jürgen; Mülhaupt, Rolf; Stark, Björn

    2002-07-01

    A novel amino acid based dimethacrylate monomer (lysineurethanedimethacrylate, LUDM) was prepared by the addition of hydroxyethylmethacrylate (HEMA) to lysinediisocyanate (LDI). The structure was confirmed by FT-IR and 1H and 13C NMR spectroscopy as well as FAB-MS. Photopolymerized LUDM exhibited low volume shrinkage upon polymerization, good mechanical properties (Young's modulus: 3740 MPa) and high thermal stability. Osteoblast adhesion and growth on polymerized LUDM samples evidenced the biocompatibility. Further improvement of the mechanical properties was obtained by using Ca-hydroxyapatite as inorganic filler varying between 10 and 30 wt%. The Young's and flexural moduli increased with increasing filler content ranging from 3740 to 5250 MPa and from 2020 to 3690 MPa, respectively. The mechanical properties and the good biocompatibility of the lysine-based methacrylate networks make them interesting materials for medical applications, e.g. bone cements, and tissue engineering. PMID:12069324

  8. [Great Scandinavian Jahre Prize 1993. Studies of cartilage and bone yields new knowledge of tissue homeostasis].

    PubMed

    Heinegård, D

    1994-01-01

    Increased knowledge of connective tissue, such as cartilage and bone, has improved our understanding of tissue replenishment under normal and pathological conditions. Although developments in this field are still at an early stage, it is already possible to discern avenues for future development leading to new diagnostic and therapeutic methods in connective tissue diseases. In this article, Dick Heinegård, the second recipient of the Jahre Prize for 1993, gives an account of his research. PMID:8121785

  9. Perinatal stem cells: A promising cell resource for tissue engineering of craniofacial bone

    PubMed Central

    Si, Jia-Wen; Wang, Xu-Dong; Shen, Steve GF

    2015-01-01

    In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application. PMID:25621114

  10. 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. PMID:21855129

  11. [Bone quality and strength relating with bone remodeling].

    PubMed

    Mori, Satoshi

    2016-01-01

    The bone has the functions of mineral reservoir and mechanical support as skeleton. Bone remodeling is the adult mode of bone metabolism, replacing old bone tissue to new one. Bone strength is determined by bone volume, structure and quality such as micro damage, degree of mineralization and collagen cross linkage, which are all controlled by bone remodeling. Bone strength decreases under high turn-over condition by decreasing bone volume and deterioration of bone structure, which also decreases under low turn-over condition by increased micro damage, increasing mineralization and AGE collagen cross linkage. PMID:26728527

  12. 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

  13. 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

    2016-01-01

    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

  14. A three-scale finite element investigation into the effects of tissue mineralisation and lamellar organisation in human cortical and trabecular bone.

    PubMed

    Vaughan, T J; McCarthy, C T; McNamara, L M

    2012-08-01

    nanoindentation results from cortical and trabecular bone. Furthermore, these studies show variations in mineral volume fraction, mineral crystal size and lamellar orientation could be responsible for previous discrepancies in experimental reports of tissue moduli. We propose that this novel multiscale modelling approach can provide a more accurate description of bone tissue properties in continuum/organ level finite element models by incorporating information regarding tissue structure and composition from advanced imaging techniques. This approach could thereby provide a preclinical tool to predict bone mechanics following prosthetic implantation or bone fracture during disease. PMID:22659366

  15. Development of a complex bone tissue culture system based on cellulose nanowhisker mechanical strain.

    PubMed

    Kim, Dae Seung; Jung, Sang-Myung; Yoon, Gwang Heum; Lee, Hoo Cheol; Shin, Hwa Sung

    2014-11-01

    In bone tissue engineering, scaffolds have been investigated for their ability to support osteoblast growth and differentiation for recovery of damaged bones. Tunicate cellulose nanowhisker (CNW) film and mechanical strain were assessed for their suitability for osteoblasts. In this study, sulfuric acid hydrolysis extraction of tunicates integuments was conducted to obtain CNWs, which were found to be acceptable for adhering, growing, and differentiating osteoblasts without cytotoxicity. Mechanical stress enhanced osteoblast differentiation, and cell survival rate was recovered at around day 3, although there was a slight increase in cell death at day 1 after stimulation. We also found that intracellular flux of calcium ion was related to increased differentiation of CNWs under mechanical stress. Overall, we demonstrated the suitability of tunicate CNWs as a scaffold for bone tissue engineering and developed a complex system based on CNW for osteoblast growth and differentiation that will be useful for bone substitute fabrication. PMID:25454753

  16. Genetic and tissue level muscle-bone interactions during unloading and reambulation.

    PubMed

    Judex, S; Zhang, W; Donahue, L R; Ozcivici, E

    2016-01-01

    Little is known about interactions between muscle and bone during the removal and application of mechanical signals. Here, we applied 3wk of hindlimb unloading followed by 3wk of reambulation to a genetically heterogeneous population of 352 adult mice and tested the hypothesis that changes in muscle are associated with changes in bone at the level of the tissue and the genome. During unloading and relative to normally ambulating control mice, most mice lost muscle and cortical bone with large variability across the population. During reambulation, individual mice regained bone and muscle at different rates. Across mice, changes in muscle and trabecular/cortical bone were not correlated to each other during unloading or reambulation. For unloading, we found one significant quantitative trait locus (QTL) for muscle area and five QTLs for cortical bone without overlap between mechano-sensitive muscle and cortical bone QTLs (but some overlap between muscle and trabecular QTLs). The low correlations between morphological changes in muscle and bone, together with the largely distinct genetic regulation of the response indicate that the premise of a muscle-bone unit that co-adjusts its size during (un)loading may need to be reassessed. PMID:27609032

  17. Pinto Bean Hull Extract Supplementation Favorably Affects Markers of Bone Metabolism and Bone Structure in Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bean hulls are rich in phenolic compounds known to possess antioxidant activity that may have beneficial effect on bone health. The aim of this study was to examine the effects of bean hull extract (BHE) from pinto beans on bone structure and serum markers in twelve-month-old male C57BL/6 mice fed e...

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

    PubMed

    Prokhonchukov, A A; Peschanskiĭ, V S

    1982-01-01

    Stereological measurements of volume fractions of 53 samples of compact and spongy structures of bones of 15 rats were carried out. The measurements were performed on cortical lamellae, trabecules and lacunae, channels of osteons and matrices of femoral, tibial and fibular bones of rats. Postflight no significant changes were seen in the above parameters as compared to the vivarium controls. During readaptation to I g a slight increase in the volume fraction of spongy bones was noted. PMID:6750237

  19. 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

    2015-01-01

    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. PMID:26400336

  20. Comparing the Immunomodulatory Properties of Bone Marrow, Adipose Tissue, and Birth-Associated Tissue Mesenchymal Stromal Cells

    PubMed Central

    Mattar, Philipp; Bieback, Karen

    2015-01-01

    Mesenchymal stromal cells (MSC) have gained immense attraction in regenerative medicine, tissue engineering, and immunotherapy. This is based on their differentiation potential and the supply of pro-regenerative and immunomodulatory signals. MSC can be isolated from a multitude of tissue sources, but mainly bone marrow, adipose tissue, and birth-associated tissues (e.g., umbilical cord, cord blood, placenta) appear to be relevant for clinical translation in immune-mediated disorders. However, only a few studies directly compared the immunomodulatory potency of MSC from different tissue sources. This review compiles the current literature regarding the similarities and differences between these three sources for MSCs with a special focus on their immunomodulatory effects on T-lymphocyte subsets and monocytes, macrophages, and dendritic cells. PMID:26579133

  1. 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

  2. [Relationships of hormones of adipose tissue and ghrelin to bone metabolism].

    PubMed

    Zofková, I

    2009-06-01

    Body adipose tissue influences bone metabolism through mechanical load, as well as via hormones released into circulation. Such hormones are adipocytokines--leptin, adiponectin, TNF-alpha, IL-6, resistin and visfatin. Some of them exert an osteoanabolic effect, while the others activate bone resorption. An increasingly discussed adipocytokine is leptin, which fundamental role is regulation of food intake ensuring survival of the organism during starvation. Leptin also stimulates osteoblasts and activates bone formation. The direct osteotropic effect of leptin is modulated by interaction with hypothalamic centers and neurohormones. Apparently, the most important leptin sensitive pathway involved in bone regulation is the beta-adrenergic system. While activation of beta-1-adrenergic receptors by leptin enhances bone formation, activation of beta-2-adrenergic receptors in hypothalamus and in the skeleton increases bone resorption. In humans, an anabolic effect on the skeleton prevails. In pubertal girls, leptin extensively released into circulation at the moment when adipose tissue reaches a critical volume, stimulates synthesis of GnRH and induces puberty, which is followed by striking increases in bone mass. Low leptin levels in anorexia nervosa are associated with amenorrhoea, which slows down increase of bone mass and may induce osteopenia. Important adipocytokine with an unambiguous negative effect on bone is adiponectin. Decreased production of this hormone explains in part the lower prevalence of osteoporosis in obese persons. In this article, the osteotropic importance ofleptin-sensitive neurohormonal mechanisms and other hormones related to adipose tissue are discussed. Clinical importance of the above mentioned hormones to integrity of the skeleton has not yet been verified. PMID:19662887

  3. Elastic poly(ε-caprolactone)-polydimethylsiloxane copolymer fibers with shape memory effect for bone tissue engineering.

    PubMed

    Kai, Dan; Prabhakaran, Molamma P; Yu Chan, Benjamin Qi; Liow, Sing Shy; Ramakrishna, Seeram; Xu, Fujian; Loh, Xian Jun

    2016-02-01

    A porous shape memory scaffold with biomimetic architecture is highly promising for bone tissue engineering applications. In this study, a series of new shape memory polyurethanes consisting of organic poly(ε-caprolactone) (PCL) segments and inorganic polydimethylsiloxane (PDMS) segments in different ratios (9 : 1, 8 : 2 and 7 : 3) was synthesised. These PCL-PDMS copolymers were further engineered into porous fibrous scaffolds by electrospinning. With different ratios of PCL: PDMS, the fibers showed various fiber diameters, thermal behaviour and mechanical properties. Even after being processed into fibrous structures, these PCL-PDMS copolymers maintained their shape memory properties, and all the fibers exhibited excellent shape recovery ratios of  >90% and shape fixity ratios of  >92% after 7 thermo-mechanical cycles. Biological assay results corroborated that the fibrous PCL-PDMS scaffolds were biocompatible by promoting osteoblast proliferation, functionally enhanced biomineralization-relevant alkaline phosphatase expression and mineral deposition. Our study demonstrated that the PCL-PDMS fibers with excellent shape memory properties are promising substrates as bioengineered grafts for bone regeneration. PMID:26836757

  4. Spectroscopic investigation on formation and growth of mineralized nanohydroxyapatite for bone tissue engineering applications

    NASA Astrophysics Data System (ADS)

    Gopi, D.; Nithiya, S.; Shinyjoy, E.; Kavitha, L.

    Synthetic calcium hydroxyapatite (HAP,Ca10(PO4)6(OH)2) is a well-known bioceramic material used in orthopaedic and dental applications because of its excellent biocompatibility and bone-bonding ability. Substitution of trace elements, such as Sr, Mg and Zn ions into the structure of calcium phosphates is the subject of widespread investigation. In this paper, we have reported the synthesis of Sr, Mg and Zn co-substituted nanohydroxyapatite by soft solution freezing method. The effect of pH on the morphology of bioceramic nanomaterial was also discussed. The in vitro bioactivity of the as-synthesized bioceramic nanomaterial was determined by soaking it in SBF for various days. The as-synthesized bioceramic nanomaterial was characterized by Fourier transform infrared spectroscopy, X- ray diffraction analysis, Scanning electron microscopy and Energy dispersive X-ray analysis and Transmission electron microscopic techniques respectively. The results obtained in our study have revealed that pH 10 was identified to induce the formation of mineralized nanohydroxyapatite. It is observed that the synthesis of bioceramic nanomaterial not only support the growth of apatite layer on its surface but also accelerate the growth which is evident from the in vitro studies. Therefore, mineralized nanohydroxyapatite is a potential candidate in bone tissue engineering.

  5. 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.

  6. 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. PMID:27263108

  7. Experimental and numerical analysis of Izod impact test of cortical bone tissue

    NASA Astrophysics Data System (ADS)

    Abdel-Wahab, A. A.; Silberschmidt, V. V.

    2012-05-01

    Bones can only sustain loads until a certain limit, beyond which they fail. Usually, the reasons for bone fracture are traumatic falls, sports injuries, and engagement in transport or industrial accidents. A proper treatment of bones and prevention of their fracture can be supported by in-depth understanding of deformation and fracture behavior of this tissue in such dynamic events. In this paper, a combination of experimental and numerical analysis was carried out in order to comprehend the fracture behavior of cortical bone tissue. Experimental tests were performed to study the transient dynamic behavior of cortical bone tissue under impact bending loading. The variability of absorbed energy for different cortex positions and notch depths was studied using Izod impact tests. Also, Extended Finite-Element Method implemented into the commercial finite-element software Abaqus was used to simulate the crack initiation and growth processes in a cantilever beam of cortical bone exposed to impact loading using the Izod loading scheme. The simulation results show a good agreement with the experimental data.

  8. [Research progress on application of carbon nanotubes in bone tissue engineering scaffold].

    PubMed

    Yao, Mengzhu; Sheng, Xiaoxia; Lin, Jun; Gao, Jianqing

    2016-03-01

    Carbon nanotubes possess excellent mechanical and electrical properties and demonstrate broad application prospects in medical fields. Carbon nanotubes are composed of inorganic materials, natural biodegradable polymer or synthetic biodegradable polymer. The composite bone tissue engineering scaffolds are constructed by particle-hole method, lyophilization, microsphere aggregation method, electrostatic spinning or three-dimensional printing. Composite scaffolds overcome the shortcomings of single material and have good biocompatibility, osteoconduction and osteoinduction. With the study of surface chemistry, toxicology, and biocompatibility, a degradable "human-friendly" carbon nanotubes composite bone tissue scaffold will be available; and under the drive of new fabrication techniques, the clinical application of carbon nanotubes composite bone tissue engineering scaffolds will be better developed. PMID:27273990

  9. Degradable and injectable poly(aldehyde guluronate) hydrogels for bone tissue engineering.

    PubMed

    Lee, K Y; Alsberg, E; Mooney, D J

    2001-08-01

    Degradable and injectable hydrogels may be ideal for bone-tissue engineering, especially in the craniofacial region because of the ease of access for injection. Alginate hydrogels potentially could be used as injectable cell delivery vehicles, but they exhibit a limited range of mechanical properties and uncontrollable disintegration time. Therefore we synthesized new hydrogels, composed of poly(aldehyde guluronate) (PAG) and adipic acid dihydrazide, that have a wide range of mechanical stiffness and controllable degradation rate. MC3T3-E1 cells adhered and multiplied on PAG hydrogels in vitro. When primary rat calvarial osteoblasts were mixed with PAG hydrogels and subcutaneously injected into the backs of mice, mineralized bone tissues were formed 9 weeks following implantation. These hydrogels may find wide utility as an injectable delivery system for bone precursor cells as well as for other applications in tissue engineering. PMID:11340593

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

    PubMed Central

    2014-01-01

    Background 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. 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. Conclusions 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. PMID:24564199

  11. Concise Review: Cell-Based Strategies in Bone Tissue Engineering and Regenerative Medicine

    PubMed Central

    Ma, Jinling; Both, Sanne K.; Yang, Fang; Cui, Fu-Zhai; Pan, Juli; Meijer, Gert J.; Jansen, John A.

    2014-01-01

    Cellular strategies play an important role in bone tissue engineering and regenerative medicine (BTE/RM). Variability in cell culture procedures (e.g., cell types, cell isolation and expansion, cell seeding methods, and preculture conditions before in vivo implantation) may influence experimental outcome. Meanwhile, outcomes from initial clinical trials are far behind those of animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the BTE/RM constructs as some complex clinical implementations require bone regeneration in too large a quantity. Coculture strategies, in which angiogenic cells are introduced into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell-based constructs. So far, preclinical studies have demonstrated that cell-based tissue-engineered constructs generally induce more bone formation compared with acellular constructs. Further, cocultures have been shown to enhance vascularization and bone formation compared with monocultures. However, translational efficacy from animal studies to clinical use requires improvement, and the role implanted cells play in clinical bone regeneration needs to be further elucidated. In view of this, the present review provides an overview of the critical procedures during in vitro and in vivo phases for cell-based strategies (both monoculture and coculture) in BTE/RM to achieve more standardized culture conditions for future studies, and hence enhance bone formation. PMID:24300556

  12. Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells

    PubMed Central

    Wang, Ping; Zhao, Liang; Liu, Jason; Weir, Michael D; Zhou, Xuedong; Xu, Hockin H K

    2014-01-01

    Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments. PMID:26273526

  13. Connexin 43 channels are essential for normal bone structure and osteocyte viability.

    PubMed

    Xu, Huiyun; Gu, Sumin; Riquelme, Manuel A; Burra, Sirisha; Callaway, Danielle; Cheng, Hongyun; Guda, Teja; Schmitz, James; Fajardo, Roberto J; Werner, Sherry L; Zhao, Hong; Shang, Peng; Johnson, Mark L; Bonewald, Lynda F; Jiang, Jean X

    2015-03-01

    Connexin (Cx) 43 serves important roles in bone function and development. Targeted deletion of Cx43 in osteoblasts or osteocytes leads to increased osteocyte apoptosis, osteoclast recruitment, and reduced biomechanical properties. Cx43 forms both gap junction channels and hemichannels, which mediate the communication between adjacent cells or between cell and extracellular environments, respectively. Two transgenic mouse models driven by a DMP1 promoter with the overexpression of dominant negative Cx43 mutants were generated to dissect the functional contribution of Cx43 gap junction channels and hemichannels in osteocytes. The R76W mutant blocks the gap junction channel, but not the hemichannel function, and the Δ130-136 mutant inhibits activity of both types of channels. Δ130-136 mice showed a significant increase in bone mineral density compared to wild-type (WT) and R76W mice. Micro-computed tomography (µCT) analyses revealed a significant increase in total tissue and bone area in midshaft cortical bone of Δ130-136 mice. The bone marrow cavity was expanded, whereas the cortical thickness was increased and associated with increased bone formation along the periosteal area. However, there is no significant alteration in the structure of trabecular bone. Histologic sections of the midshaft showed increased apoptotic osteocytes in Δ130-136, but not in WT and R76W, mice which correlated with altered biomechanical and estimated bone material properties. Osteoclasts were increased along the endocortical surface in both transgenic mice with a greater effect in Δ130-136 mice that likely contributed to the increased marrow cavity. Interestingly, the overall expression of serum bone formation and resorption markers were higher in R76W mice. These findings suggest that osteocytic Cx43 channels play distinctive roles in the bone; hemichannels play a dominant role in regulating osteocyte survival, endocortical bone resorption, and periosteal apposition, and gap

  14. Connexin 43 Channels are Essential for Normal Bone Structure and Osteocyte Viability

    PubMed Central

    Xu, Huiyun; Gu, Sumin; Riquelme, Manuel A.; Burra, Sirisha; Callaway, Danielle; Cheng, Hongyun; Guda, Teja; Schmitz, James; Fajardo, Roberto J.; Werner, Sherry L.; Zhao, Hong; Shang, Peng; Johnson, Mark L.; Bonewald, Lynda F.; Jiang, Jean X.

    2014-01-01

    Connexin (Cx) 43 serves important roles in bone function and development. Targeted deletion of Cx43 in osteoblasts or osteocytes leads to increased osteocyte apoptosis, osteoclast recruitment, and reduced biomechanical properties. Cx43 forms both gap junction channels and hemichannels, which mediate the communication between adjacent cells or between cell and extracellular environments, respectively. Two transgenic mouse models driven by a DMP1 promoter with the overexpression of dominant negative Cx43 mutants were generated to dissect the functional contribution of Cx43 gap junction channels and hemichannels in osteocytes. The R76W mutant blocks gap junction channel, but not hemichannel function, and the Δ130-136 mutant inhibits activity of both types of channels. Δ130-136 mice showed a significant increase in bone mineral density compared to WT and R76W mice. MicroCT analyses revealed a significant increase in total tissue and bone area in midshaft cortical bone of Δ130-136 mice. The bone marrow cavity was expanded, whereas the cortical thickness was increased and associated with increased bone formation along the periosteal area. However, there is no significant alteration in the structure of trabecular bone. Histologic sections of the midshaft showed increased apoptotic osteocytes in Δ130-136, but not in WT and R76W, mice which correlated with altered biomechanical and estimated bone material properties. Osteoclasts were increased along the endocortical surface in both transgenic mice with a greater effect in Δ130-136 mice which likely contributed to the increased marrow cavity. Interestingly, the overall expression of serum bone formation and resorption markers were higher in R76W mice. These findings suggest that osteocytic Cx43 channels play distinctive roles in the bone; hemichannels play a dominant role in regulating osteocyte survival, endocortical bone resorption and periosteal apposition, and gap junction communication is involved in the process of

  15. 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.

  16. A Novel Local Autologous Bone Graft Donor Site After Scalp Tissue Expansion in Aplasia Cutis Congenita.

    PubMed

    Hadad, Ivan; Meara, John G; Rogers-Vizena, Carolyn R

    2016-06-01

    Aplasia cutis congenita (ACC) is a rare condition often presenting as an absent area of cutaneous scalp. The calvarium and dura may also be affected. Scalp reconstruction with tissue expansion is often needed for large defects. Patients involving deficient calvarial bone present a dilemma for the reconstructive surgeon, because bone graft donor sites are limited in young children.A thick, bony rim has been noted to form around the periphery of scalp tissue expanders. The authors present a series of 3 patients with ACC for whom this bony hyperostosis was used as donor particulate bone graft at the time of scalp tissue expansion. There was 85 to 100% graft ossification on postoperative computed tomography scan. There were no bone graft-related complications.In conclusion, the hyperostotic rim that forms after scalp tissue expansion can be successfully used as particulate bone graft, decreasing the number of procedures needed for patient with ACC and obviating the need for other donor sites. PMID:27192637

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

    PubMed

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

    2011-12-01

    The goal of research was study of restoration processes in jaw-teeth bone defects by application of osteoplastic materials in the experiment. The experiment was performed over 32 white (6-12 month old) rats; the animals were divided into 2 groups; 16 animals were enrolled in the first group; the section was performed in the edge of lower jaw; the lower jaw body was revealed. Under the effect of the dental drilling machine and the # 1 cooling mean by the fissure bohrium (distilled water) the defect of the dimension of 2x2 mm was created; the defect was washed by 0/9% saline to remove the bone sawdust; the wound was sutured tightly, in layers. The second group of the experiment was staffed with 16 animals (main group); the similar bone defect of the size 2 x 2mm was created on the rat's jaw's body. After washing of modeled defect we inserted osteopathic materials PORESORB-TCP crystals with the size of 0,6-1.0 mm the wound was sutured tightly, in layers. After the 3-rd, 15-th, 30-th and 90-th days from the date of operation there was performed X-ray and morphological examination over the animals in the control as well as the main group. The analysis of the examination performed over the experimental materials showed that in the control group in samples taken at 90th day the defects were not completely restored. In the test group in samples taken at 90th day reparative regeneration is confirmed. This is stimulated by the factor that within the main group's animals the defect regeneration process is supported with the osteoplastic material PORESORB-TCP. PMID:22306506

  18. Comparison of Bone Tissue Elements Between Normal and Osteoarthritic Pelvic Bones in Dogs.

    PubMed

    Nganvongpanit, Korakot; Buddhachat, Kittisak; Brown, Janine L

    2016-06-01

    Physiochemical analysis of bones affected with osteoarthritis (OA) can be used to better understand the etiology of this disease. We investigated the percentage of chemical elements in canine pelvic bone affected with varying degrees of OA using a handheld X-ray fluorescence (XRF) analyzer that discriminates magnesium (Mg(12)) through bismuth (Bi(83)). A total of 45 pelvic bones, including both ilium and subchondral acetabular bone plates, were categorized as normal (n = 20), mild grade OA (n = 5), moderate grade OA (n = 15), and severe grade OA (n = 5). In normal pelvic, seven elements (P, Ca, Mn, Ag, Cd, Sn, and Sb) differed (p < 0.005) in percentage between ilium and acetabulum. Comparisons among the four OA groups found Mn and Fe to be highest in severe grades (p < 0.05) in both ilium and acetabulum. Three heavy metals (Ag, Sn, and Sb) were detected in high percentages (p < 0.05) in the severe OA group in the acetabulum, but in ilium only Sn was high (p < 0.05) in severe OA. In conclusion, the percentages of several elements differed between pelvic types in dogs, and also with increasing severity of OA. The finding of high Mn and Fe in severe grade OA bone suggests these two elements may be useful in future studies of the etiology and pathophysiology of OA. PMID:26537116

  19. Preparation of a biomimetic composite scaffold from gelatin/collagen and bioactive glass fibers for bone tissue engineering.

    PubMed

    Sharifi, Esmaeel; Azami, Mahmoud; Kajbafzadeh, Abdol-Mohammad; Moztarzadeh, Fatollah; Faridi-Majidi, Reza; Shamousi, Atefeh; Karimi, Roya; Ai, Jafar

    2016-02-01

    Bone tissue is a composite material made of organic and inorganic components. Bone tissue engineering requires scaffolds that mimic bone nature in chemical and mechanical properties. This study proposes a novel method for preparing composite scaffolds that uses sub-micron bioglass fibers as the organic phase and gelatin/collagen as the inorganic phase. The scaffolds were constructed by using freeze drying and electro spinning methods and their mechanical properties were enhanced by using genipin crosslinking agent. Electron microscopy micrographs showed that the structure of composite scaffolds were porous with pore diameters of approximately 70-200μm, this was again confirmed by mercury porosimetery. These pores are suitable for osteoblast growth. The diameters of the fibers were approximately 150-450nm. Structural analysis confirmed the formation of desirable phases of sub-micron bioglass fibers. Cellular biocompatibility tests illustrated that scaffolds containing copper ion in the bioglass structure had more cell growth and osteoblast attachment in comparison to copper-free scaffolds. PMID:26652405

  20. 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.

  1. Relationships between tissue composition and viscoelastic properties in human trabecular bone.

    PubMed

    Ojanen, X; Isaksson, H; Töyräs, J; Turunen, M J; Malo, M K H; Halvari, A; Jurvelin, J S

    2015-01-21

    Trabecular bone is a metabolically active tissue with a high surface to volume ratio. It exhibits viscoelastic properties that may change during aging. Changes in bone properties due to altered metabolism are sensitively revealed in trabecular bone. However, the relationships between material composition and viscoelastic properties of bone, and their changes during aging have not yet been elucidated. In this study, trabecular bone samples from the femoral neck of male cadavers (n=21) aged 17-82 years were collected and the tissue level composition and its associations with the tissue viscoelastic properties were evaluated by using Raman microspectroscopy and nanoindentation, respectively. For composition, collagen content, mineralization, carbonate substitution and mineral crystallinity were evaluated. The calculated mechanical properties included reduced modulus (Er), hardness (H) and the creep parameters (E1, E2, η1and η2), as obtained by fitting the experimental data to the Burgers model. The results indicated that the creep parameters, E1, E2, η1and η2, were linearly correlated with mineral crystallinity (r=0.769-0.924, p<0.001). Creep time constant (η2/E2) tended to increase with crystallinity (r=0.422, p=0.057). With age, the mineralization decreased (r=-0.587, p=0.005) while the carbonate substitution increased (r=0.728, p<0.001). Age showed no significant associations with nanoindentation parameters. The present findings suggest that, at the tissue-level, the viscoelastic properties of trabecular bone are related to the changes in characteristics of bone mineral. This association may be independent of human age. PMID:25498367

  2. Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study.

    PubMed

    Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali

    2016-10-01

    Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan-gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan-gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan-gelatin scaffolds. Implantation of both the gelatin and chitosan-gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P < 0.05). Combination of the gelatin and chitosan considerably increased structural and functional properties of the healing bones when compared to chitosan scaffold (P < 0.05). However, no significant differences were observed between the gelatin and gelatin-chitosan groups in these regards (P > 0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects. PMID:27590825

  3. Change in temperature of subjacent bone during soft tissue laser ablation.

    PubMed

    Spencer, P; Cobb, C M; Wieliczka, D M; Glaros, A G; Morris, P J

    1998-11-01

    In tissues that closely approximate bone, sufficient heat may be transferred to the bone during laser surgery to cause damage and/or necrosis. To date, there have been few studies examining the temperatures elicited at the bone surface as a result of laser application to the overlying soft tissues. The purpose of this investigation was to determine, under in vitro conditions, temperature changes at the bone/soft tissue interface during laser ablation with CO2 and Nd:YAG lasers used with and without (w/wo) air/water coolant. Experimental specimens consisted of 5 mandibles from freshly sacrificed hogs; laser treatment sites were the buccal and lingual attached gingiva of the molars and the lingual keratinized mucosa of the incisor region. CO2 and Nd:YAG lasers were used w/wo coolant at power settings of 4 to 8 W and 5 to 9 W, respectively. Temperature changes were measured with a copper constant thermocouple contained within a 21 gauge hypodermic needle. In comparing the lasers at comparable energy densities w/wo coolant, temperature increases at the bone/soft tissue interface ranged from 8.0 to 11.1 degrees C with the Nd:YAG and 1.4 to 2.1 degrees C with the CO2. Similarly, in comparing the times required for the interface to return to baseline temperature following removal of the laser, values ranged from approximately 143 to 205 and approximately 119 to 139 seconds for the Nd:YAG and CO2, respectively. Results from this study suggest that, at energy densities equal or above those reported here, the increase in temperature at the bone surface as a result of periodontal soft tissue surgery with the Nd:YAG laser could be damaging, especially if the exposure is prolonged. PMID:9848538

  4. Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells.

    PubMed

    Gao, Guifang; Schilling, Arndt F; Yonezawa, Tomo; Wang, Jiang; Dai, Guohao; Cui, Xiaofeng

    2014-10-01

    Bioprinting based on thermal inkjet printing is a promising but unexplored approach in bone tissue engineering. Appropriate cell types and suitable biomaterial scaffolds are two critical factors to generate successful bioprinted tissue. This study was undertaken in order to evaluate bioactive ceramic nanoparticles in stimulating osteogenesis of printed bone marrow-derived human mesenchymal stem cells (hMSCs) in poly(ethylene glycol)dimethacrylate (PEGDMA) scaffold. hMSCs suspended in PEGDMA were co-printed with nanoparticles of bioactive glass (BG) and hydroxyapatite (HA) under simultaneous polymerization so the printed substrates were delivered with highly accurate placement in three-dimensional (3D) locations. hMSCs interacted with HA showed the highest cell viability (86.62 ± 6.02%) and increased compressive modulus (358.91 ± 48.05 kPa) after 21 days in culture among all groups. Biochemical analysis showed the most collagen production and highest alkaline phosphatase activity in PEG-HA group, which is consistent with gene expression determined by quantitative PCR. Masson's trichrome staining also showed the most collagen deposition in PEG-HA scaffold. Therefore, HA is more effective comparing to BG for hMSCs osteogenesis in bioprinted bone constructs. Combining with our previous experience in vasculature, cartilage, and muscle bioprinting, this technology demonstrates the capacity for both soft and hard tissue engineering with biomimetic structures. PMID:25130390

  5. [The transplantability of bone marrow and spleen cells after filtration through silon tissue].

    PubMed

    Fiala, J

    1976-01-01

    Investigations were carried out on the separation of haematopoietic stem cells from suspensions of the bone-marrow and spleen by means of filtration with silon tissue. The presence of stem cells in the filtrates was determined by the spleen colony test according to the method of Till and McCulloch in irradiated mice. The investigations revealed that a selective separation of haematopoietic stem cells could not be achieved when proceeding in this way. From the results of further test series, in which suspensions were also used which had been gained from haematopoietic tissues of hypersplenic mice, the conclusion could be drawn that the haematopoietic stem cells obtained by filtrating the bone-marrow will have another affinity to the spleen tissue of irradiated mice than the haematopoietic stem cells gained by filtrating the spleen tissue. PMID:64407

  6. Quantification of fluid shear stress in bone tissue engineering scaffolds with spherical and cubical pore architectures.

    PubMed

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

    2016-06-01

    Recent studies have shown that mechanical stimulation, in the form of fluid perfusion and mechanical compression, can enhance osteogenic differentiation of mesenchymal stem cells and bone cells within tissue engineering scaffolds in vitro. The precise nature of mechanical stimulation within tissue engineering scaffolds is not only dictated by the exogenously applied loading regime, but also depends on the geometric features of the scaffold, in particular architecture, pore size and porosity. However, the precise contribution of each geometric feature towards the resulting mechanical stimulation within a scaffold is difficult to characterise due to the wide range of interacting parameters. In this study, we have applied a fluid-structure interaction model to investigate the role of scaffold geometry (architecture, pore size and porosity) on pore wall shear stress (WSS) under a range of different loading scenarios: fluid perfusion, mechanical compression and a combination of perfusion and compression. It is found that scaffold geometry (spherical and cubical pores), in particular the pore size, has a significant influence on the stimulation within scaffolds. Furthermore, we observed an amplified WSS within scaffolds under a combination of fluid perfusion and mechanical compression, which exceeded that caused by individual fluid perfusion or mechanical compression approximately threefold. By conducting this comprehensive parametric variation study, an expression was generated to allow the design and optimisation of 3D TE scaffolds and inform experimental loading regimes so that a desired level of mechanical stimulation, in terms of WSS is generated within the scaffold. PMID:26224148

  7. [Microdestruction of the bone].

    PubMed

    Iankovskiĭ, V É

    2014-01-01

    The objective of the present study was the detection of microcracks in the compact bone tissue surrounding the fracture and in deformed bone undergoing subcritical loading. The portions of deformed bone tissue and terminal fragments of broken bones were obtained in the form of blocks longitudinally sawcut from the regions of primary and secondary bone rupture. A total of 300 such blocks were available for the examination. All portions of the deformed bone tissue and terminal fragments of broken bones showed up microcracks commensurate with the bone structures. They were actually hardened traces of deformation that preceded the fracture and reflected the volume of the destroyed bone tissue; moreover, in certain cases they allowed to identify the kind of the object that exerted the external action (either a blow or slow bending). PMID:25269164

  8. 3D Scaffolds with Different Stiffness but the Same Microstructure for Bone Tissue Engineering.

    PubMed

    Chen, Guobao; Dong, Chanjuan; Yang, Li; Lv, Yonggang

    2015-07-29

    A growing body of evidence has shown that extracellular matrix (ECM) stiffness can modulate stem cell adhesion, proliferation, migration, differentiation, and signaling. Stem cells can feel and respond sensitively to the mechanical microenvironment of the ECM. However, most studies have focused on classical two-dimensional (2D) or quasi-three-dimensional environments, which cannot represent the real situation in vivo. Furthermore, most of the current methods used to generate different mechanical properties invariably change the fundamental structural properties of the scaffolds (such as morphology, porosity, pore size, and pore interconnectivity). In this study, we have developed novel three-dimensional (3D) scaffolds with different degrees of stiffness but the same 3D microstructure that was maintained by using decellularized cancellous bone. Mixtures of collagen and hydroxyapatite [HA: Ca10(PO4)6(OH)2] with different proportions were coated on decellularized cancellous bone to vary the stiffness (local stiffness, 13.00 ± 5.55 kPa, 13.87 ± 1.51 kPa, and 37.7 ± 19.6 kPa; bulk stiffness, 6.74 ± 1.16 kPa, 8.82 ± 2.12 kPa, and 23.61 ± 8.06 kPa). Microcomputed tomography (μ-CT) assay proved that there was no statistically significant difference in the architecture of the scaffolds before or after coating. Cell viability, osteogenic differentiation, cell recruitment, and angiogenesis were determined to characterize the scaffolds and evaluate their biological responses in vitro and in vivo. The in vitro results indicate that the scaffolds developed in this study could sustain adhesion and growth of rat mesenchymal stem cells (MSCs) and promote their osteogenic differentiation. The in vivo results further demonstrated that these scaffolds could help to recruit MSCs from subcutaneous tissue, induce them to differentiate into osteoblasts, and provide the 3D environment for angiogenesis. These findings showed that the method we developed can build scaffolds with

  9. Bone and soft tissue sarcomas during pregnancy: A narrative review of the literature.

    PubMed

    Zarkavelis, George; Petrakis, Dimitrios; Fotopoulos, George; Mitrou, Sotirios; Pavlidis, Nicholas

    2016-07-01

    Bone or soft tissue sarcomas are rarely diagnosed during pregnancy. Until today 137 well documented cases have been reported in the English literature between 1963 and 2014. Thirty-eight pregnant mothers were diagnosed with osteosarcoma, Ewing's sarcoma or chondrosarcoma, whereas 95 other cases of soft tissue sarcomas of various types have been documented. We present the clinical picture and therapeutic management of this coexistence. PMID:27408761

  10. One-pot synthesis of magnetic, macro/mesoporous bioactive glasses for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Wang, Dan; Lin, Huiming; Jiang, Jingjie; Han, Xiao; Guo, Wei; Wu, Xiaodan; Jin, Yingxue; Qu, Fengyu

    2013-04-01

    Magnetic and macro/mesoporous bioactive glasses were synthesized by a one-pot method via a handy salt leaching technique. It was identified to be an effective and simple synthetic strategy. The non-ionic triblock copolymer, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123), was used as the structure directing agent for mesoporous structure but also as the reductant to reduce the iron source into magnetic iron oxide. The prepared materials exhibited excellent super-paramagnetic property with interconnected macroporous (200-300 μm) and mesoporous (3.4 nm) structure. Furthermore, their outstanding drug storage/release properties and rapid (5) induction of hydroxyapatite growth ability were investigated after immersing in simulated body fluid solution at 37 °C. Notably, the biocompatibility assessment confirmed that the materials obtained presented good biocompatibility and enhanced adherence of HeLa cells. Herein, the novel materials are expected to have potential application for bone tissue engineering.

  11. Risk factors for hematological toxicity of chemotherapy for bone and soft tissue sarcoma.

    PubMed

    Ouyang, Zhengxiao; Peng, Dan; Dhakal, Dibya Purush

    2013-05-01

    The aim of this study was to assess chemotherapy treatment characteristics, neutropenic event occurrence and related risk factors in bone and soft tissue sarcoma patients in China. Knowledge of such risk factors aids healthcare providers in focusing resources on those who are at most risk and targeting prophylactic colony-stimulating factors (CSFs) for those patients. The study included 113 children and adults with different types of sarcoma who had been treated with neoadjuvant chemotherapy for bone and soft tissue sarcoma in order to identify risk factors for hematological toxicity of chemotherapy for bone and soft tissue sarcoma. Risk factors were determined using multivariate logistic regression analysis. Factors such as age <20 years, Karnofsky Performance Status Scale (KPS) score <60, malnutrition, number of previous chemotherapies >3 and combination therapy with >3 drugs were significantly associated with occurrence of grade III/IV neutropenia, suggestive of severe bone marrow suppression. Patients with such characteristics are at most risk of severe bone marrow suppression, and preventing discontinuation of treatment would be valuable for treating patients more effectively. PMID:23760066

  12. Mechanisms of fluid-flow-induced matrix production in bone tissue engineering.

    PubMed

    Morris, H L; Reed, C I; Haycock, J W; Reilly, G C

    2010-12-01

    Matrix production by tissue-engineered bone is enhanced when the growing tissue is subjected to mechanical forces and/or fluid flow in bioreactor culture. Cells deposit collagen and mineral, depending upon the mechanical loading that they receive. However, the molecular mechanisms of flow-induced signal transduction in bone are poorly understood. The hyaluronan (HA) glycocalyx has been proposed as a potential mediator of mechanical forces in bone. Using a parallel-plate flow chamber the effects of removal of HA on flow-induced collagen production and NF-kappaB activation in MLO-A5 osteoid osteocytes were investigated. Short periods of fluid flow significantly increased collagen production and induced translocation of the NF-kappaB subunit p65 to the cell's nuclei in 65 per cent of the cell population. Enzymatic removal of the HA coat and antibody blocking of CD44 (a transmembrane protein that binds to HA) eliminated the fluid-flow-induced increase in collagen production but had no effect on the translocation of p65. HA and CD44 appear to play roles in transducing the flow signals that modulate collagen production over long-term culture but not in the short-term flow-induced activation of NF-kappaB, implying that multiple signalling events are initiated from the commencement of flow. Understanding the mechanotransduction events that enable fluid flow to stimulate bone matrix production will allow the optimization of bioreactor design and flow profiles for bone tissue engineering. PMID:21287834

  13. Prediction of Local Ultimate Strain and Toughness of Trabecular Bone Tissue by Raman Material Composition Analysis

    PubMed Central

    Stüssi, Edgar; Müller, Ralph

    2015-01-01

    Clinical studies indicate that bone mineral density correlates with fracture risk at the population level but does not correlate with individual fracture risk well. Current research aims to better understand the failure mechanism of bone and to identify key determinants of bone quality, thus improving fracture risk prediction. To get a better understanding of bone strength, it is important to analyze tissue-level properties not influenced by macro- or microarchitectural factors. The aim of this pilot study was to identify whether and to what extent material properties are correlated with mechanical properties at the tissue level. The influence of macro- or microarchitectural factors was excluded by testing individual trabeculae. Previously reported data of mechanical parameters measured in single trabeculae under tension and bending and its compositional properties measured by Raman spectroscopy was evaluated. Linear and multivariate regressions show that bone matrix quality but not quantity was significantly and independently correlated with the tissue-level ultimate strain and postyield work (r = 0.65–0.94). Principal component analysis extracted three independent components explaining 86% of the total variance, representing elastic, yield, and ultimate components according to the included mechanical parameters. Some matrix parameters were both included in the ultimate component, indicating that the variation in ultimate strain and postyield work could be largely explained by Raman-derived compositional parameters. PMID:25695083

  14. Poly(caprolactone) based magnetic scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Bañobre-López, M.; Piñeiro-Redondo, Y.; De Santis, R.; Gloria, A.; Ambrosio, L.; Tampieri, A.; Dediu, V.; Rivas, J.

    2011-04-01

    Synthetic scaffolds for tissue engineering coupled to stem cells represent a promising approach aiming to promote the regeneration of large defects of damaged tissues or organs. Magnetic nanocomposites formed by a biodegradable poly(caprolactone) (PCL) matrix and superparamagnetic iron doped hydroxyapatite (FeHA) nanoparticles at different PCL/FeHA compositions have been successfully prototyped, layer on layer, through 3D bioplotting. Magnetic measurements, mechanical testing, and imaging were carried out to calibrate both model and technological processing in the magnetized scaffold prototyping. An amount of 10% w/w of magnetic FeHA nanoparticles represents a reinforcement for PCL matrix, however, a reduction of strain at failure is also observed. Energy loss (absorption) measurements under a radio-frequency applied magnetic field were performed in the resulting magnetic scaffolds and very promising heating properties were observed, making them very useful for potential biomedical applications.

  15. Trabecular bone structural variation throughout the human lower limb.

    PubMed

    Saers, Jaap P P; Cazorla-Bak, Yasmin; Shaw, Colin N; Stock, Jay T; Ryan, Timothy M

    2016-08-01

    Trabecular bone is responsive to mechanical loading, and thus may be a useful tool for interpreting past behaviour from fossil morphology. However, the ability to meaningfully interpret variation in archaeological and hominin trabecular morphology depends on the extent to which trabecular bone properties are integrated throughout the postcranium or are locally variable in response to joint specific loading. We investigate both of these factors by comparing trabecular bone throughout the lower limb between a group of highly mobile foragers and two groups of sedentary agriculturalists. Trabecular bone structure is quantified in four volumes of interest placed within the proximal and distal joints of the femur and tibia. We determine how trabecular structures correspond to inferred behavioural differences between populations and whether the patterns are consistent throughout the limb. A significant correlation was found between inferred mobility level and trabecular bone structure in all volumes of interest along the lower limb. The greater terrestrial mobility of foragers is associated with higher bone volume fraction, and thicker and fewer trabeculae (lower connectivity density). In all populations, bone volume fraction decreases while anisotropy increases proximodistally throughout the lower limb. This observation mirrors reductions in cortical bone mass resulting from proximodistal limb tapering. The reduction in strength associated with reduced bone volume fraction may be compensated for by the increased anisotropy in the distal tibia. A similar pattern of trabecular structure is found throughout the lower limb in all populations, upon which a signal of terrestrial mobility appears to be superimposed. These results support the validity of using lower limb trabecular bone microstructure to reconstruct terrestrial mobility levels from the archaeological and fossil records. The results further indicate that care should be taken to appreciate variation resulting from

  16. Reliability of structure tensors in representing soft tissues structure.

    PubMed

    Lanir, Yoram; Namani, Ravi

    2015-06-01

    Structure tensors have been applied as descriptors of tissue morphology for constitutive modeling. Here the reliability of these tensors in representing tissues structure is investigated by model simulations of a few examples of generated and measured planar fiber orientation distributions. Reliability was evaluated by comparing the data with the orientation density distribution recovered from the structure tensor representation, and with a orientation density recovered from an alternative representation by Fourier series of spherical harmonics. The results show that except for the case of uniform or close to uniform orientation distributions, the distributions recovered from the structure tensor fit the data poorly. On the other hand, orientation distributions recovered from Fourier series of spherical harmonics converge to the data distributions provided sufficient terms are included in the truncated series. These results suggest that the structure tensor is a reliable descriptor of tissue structure only under very limited cases. PMID:25828155

  17. 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. PMID:18315815

  18. 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.

  19. Dynamic Acoustic Radiation Force Retains Bone Structural and Mechanical Integrity in a Functional Disuse Osteopenia Model

    PubMed Central

    Uddin, Sardar M. Z.; Qin, Yi-Xian

    2015-01-01

    Disuse osteopenia and bone loss have been extensively reported in long duration space mission and long term bed rest. The pathology of the bone loss is similar to osteoporosis but highly confined to weight bearing bones. The current anabolic and/or anti-resorptive drugs have systemic effects and are costly over extended time, with concerns of long term fracture risk. This study use Low Intensity Pulsed Ultrasound (LIPUS) as a non-invasive acoustic force and anabolic stimulus to countermeasure disuse induced bone loss. Four-month old C57BL/6 mice were randomized to five groups, 1) age-matched (AM), 2) non-suspended sham (NS), 3) nonsuspended –LIPUS (NU), 4) suspended sham (SS), and 5) suspended-LIPUS (SU) groups. After four weeks of suspension, µCT analyses showed significant decreases in trabecular bone volume fraction (BV/TV) (−36%, p<0.005), bone tissue mineral density (TMD) (−3%, p<0.05), trabecular thickness (Tb.Th) (−12.5%, p<0.005), and increase in bone surface/bone volume (+BS/BV) (+16%, p<0.005), relative to age-matched (AM). Application of LIPUS for 20 min/day for 5 days/week, significantly increased TMD (+3%, p<0.05), Tb.Th (+6%, p<0.05), and decreased BS/BV (−10%, p<0.005), relative to suspension alone (SS) mice. Histomorphometry analyses showed a breakdown of bone microstructure under disuse conditions consist with µCT results. In comparison to SS mice, LIPUS treated bone showed increased structural integrity with increased bone formation rates at metaphysical endosteal and trabecular surfaces (+0.104±0.07 vs 0.031±0.30 µm3/µm2/d) relative to SS. Four-point bending mechanical tests of disused SS femurs showed reduced elastic modulus (−53%, p<0.05), yield (−33%, p<0.05) and ultimate strength (−45%, p<0.05) at the femoral diaphysis relative to AM bone. LIPUS stimulation mitigated the adverse effects of disuse on bone elastic modulus (+42%, p<0.05), yield strength (+29%, p<0.05), and ultimate strength (+39%, p<0.05) relative to SS

  20. Researches of mechanical behavior of bone tissues for development and selection of individual ceramic implants

    NASA Astrophysics Data System (ADS)

    Kolmakova, T. V.; Buyakova, S. P.; Kulkov, S. N.

    2016-04-01

    The researches of mechanical behavior were conducted and the effective mechanical properties of model compact bone micro volumes under uniaxial compression were obtained taking into account the structural characteristics and the mineral content; experimental analysis of the mechanical behavior and the effective mechanical parameters of obtained porous zirconia ceramics were conducted. The comparison of obtained in paper calculated and experimental mechanical properties of bone and ceramics was carry out and the recommendations on the use the ceramics with certain porosity to replace the compact bone fragment with a certain structure and mineral content were suggested.

  1. [Experimental study of dental implants with nanostructured non-resorbable coating integration into bone tissue].

    PubMed

    Grigor'ian, A S; Khamraev, T K; Toporkova, A K; Amirov, A R

    2010-01-01

    In 2 dogs on both sides of mandible premolars were removed. In 3 months after dental alveolus healing intraosseous screwdriver dental implants (Konmet, Russia) were installed in the place of the removed teeth. Analogous operation was done on the contralateral side: the same type of implants were installed but with new nanostructured multifunctional biocompatible non-resorbable coating (MBNC) of the Ti-Ca-P-C-O-N composition. The animals were taken out of the experiment in 4 months after implants installation and implant-bone blocks were studied by SEM-method. According to the SEM-data in the region of the contact of implant-bone without new MBNC only fibrous connective tissue was formed. In case when MBNC was used the close welding of bone tissue with implant surface was observed that was considered as sign of osteointegration. PMID:21186642

  2. Morpho-functional adaptations in the bone tissue under the space flight conditions.

    PubMed

    Rodionova, N V; Oganov, V S

    2001-07-01

    Microgravity in space flight--situation of a maximum deficit of supporting loading on the skeleton and good model for finding-out of osteopenia and osteoporosis development laws, which are wide-spreading now and are "civilization diseases". Most typical for bones in conditions of a microgravitation by changes are: a decrease of intensity growth and osteoplastic processes, osteopenia and osteoporosis, decreasing of a mechanical strength and the risk of breaches arising (Oganov V.S., Schneider V. (1996)). Cytological mechanisms of gravity-dependent reactions in a bone tissue remain in many respects not-clear. By the purpose of our work was the analysis of some ultrastructural changes in bone tissue cells of the monkeys (Macaca mulatta), staying during two weeks onboard the biosatellite BION -11. PMID:12650186

  3. In vitro cell proliferation evaluation of porous nano-zirconia scaffolds with different porosity for bone tissue engineering.

    PubMed

    Zhu, Yinglan; Zhu, Ruiqiao; Ma, Juan; Weng, Zhiqiang; Wang, Yang; Shi, Xiaolei; Li, Yicai; Yan, Xiaodong; Dong, Zhen; Xu, Jinke; Tang, Chengzhong; Jin, Lei

    2015-09-01

    The selection of scaffold materials and the optimization of scaffold morphological and mechanical properties are critical for successful bone tissue engineering. We fabricated porous scaffolds of nano-sized zirconia using a replication technique. The study aimed to explore the relationship between porosity, pore size, mechanical strength, cell adhesion, and cell proliferation in the zirconia scaffolds. Macro- and micro-structures and compressive strength were comparatively tested. Beagle bone marrow stromal cells were seeded onto the scaffolds to evaluate cell seeding efficiency and cell proliferation profile over 14 d of incubation. The zirconia scaffolds presented a complex porous structure with good interconnectivity of pores. By increasing the sinter cycles, the porosity and pore size of the scaffolds decreased, with mean values ranging from 92.7-68.0% and 830-577 μm, respectively, accompanied by increased compressive strengths of 0.6-4.4 MPa. Cell seeding efficiency and cell proliferation over the first 7 d of incubation increased when the porosity decreased, with cell viability highest in the scaffold with a porosity of 75.2%. After 7 d of incubation, the cell proliferation increased when the porosity increased, highest in the scaffolds with a porosity of 92.7%. These results showed that the zirconia scaffold with a porosity of 75.2% possesses favorable mechanical and biological properties for future applications in bone tissue engineering. PMID:26391576

  4. The structure and micromechanics of elastic tissue

    PubMed Central

    Green, Ellen M.; Mansfield, Jessica C.; Bell, James S.; Winlove, C. Peter

    2014-01-01

    Elastin is a major component of tissues such as lung and blood vessels, and endows them with the long-range elasticity necessary for their physiological functions. Recent research has revealed the complexity of these elastin structures and drawn attention to the existence of extensive networks of fine elastin fibres in tissues such as articular cartilage and the intervertebral disc. Nonlinear microscopy, allowing the visualization of these structures in living tissues, is informing analysis of their mechanical properties. Elastic fibres are complex in composition and structure containing, in addition to elastin, an array of microfibrillar proteins, principally fibrillin. Raman microspectrometry and X-ray scattering have provided new insights into the mechanisms of elasticity of the individual component proteins at the molecular and fibrillar levels, but more remains to be done in understanding their mechanical interactions in composite matrices. Elastic tissue is one of the most stable components of the extracellular matrix, but impaired mechanical function is associated with ageing and diseases such as atherosclerosis and diabetes. Efforts to understand these associations through studying the effects of processes such as calcium and lipid binding and glycation on the mechanical properties of elastin preparations in vitro have produced a confusing picture, and further efforts are required to determine the molecular basis of such effects. PMID:24748954

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

    PubMed Central

    Romagnoli, Cecilia; Brandi, Maria Luisa

    2014-01-01

    Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians. Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility, biodegradability and osteoinductivity. Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells (MSCs). In particular, a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue. These adipose stem cells (ASCs) can be obtained in large quantities with little donor site morbidity or patient discomfort, in contrast to the invasive and painful isolation of bone marrow MSCs. The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models, with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients. Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration, the lack of standardization in applied techniques makes the comparison between studies difficult. Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns, which must be resolved to permit application in regenerative medicine. PMID:24772241

  6. Bone Tissue Engineering with Multilayered Scaffolds-Part II: Combining Vascularization with Bone Formation in Critical-Sized Bone Defect.

    PubMed

    Sathy, Binulal Nelson; Watson, Brendan M; Kinard, Lucas A; Spicer, Patrick P; Dahlin, Rebecca L; Mikos, Antonios G; Nair, Shantikumar

    2015-10-01

    Our previous in vivo study showed that multilayered scaffolds made of an angiogenic layer embedded between an osteogenic layer and an osteoconductive layer, with layer thickness in the 100-400 μm range, resulted in through-the-thickness vascularization of the construct even in the absence of exogenous endothelial cells. The angiogenic layer was a collagen-fibronectin gel, and the osteogenic layer was made from nanofibrous polycaprolactone while the osteoconductive layer was made either from microporous hydroxyapatite or microfibrous polycaprolactone. In this follow-up study, we implanted these acellular and cellular multilayered constructs in critical-sized rat calvarial defects and evaluated their vascularization and bone formation potential. Vascularization and bone formation at the defect were evaluated and quantified using microcomputed tomography (microCT) followed by perfusion of the animals with the radio opaque contrast agent, MICROFIL. The extent of bony bridging and union within the critical-sized defect was evaluated using a previously established scoring system from the microCT data set. Similarly the new bone formation in the defect was quantified from the microCT data set as previously reported. Histological evaluation at 4 and 12 weeks validated the microCT findings. Our experimental results showed that acellular multilayered scaffolds with microscale-thick nanofibers and porous ceramic discs with angiogenic zone at their interface can regenerate functional vasculature and bone similar to that of cellular constructs in critical-sized calvarial defects. This result suggests that suitably bioengineered acellular multilayered constructs can be an improved and more translational approach in functional in vivo bone regeneration. PMID:26262560

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

    PubMed Central

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

    2010-01-01

    The repair of critical-sized bone defects is still challenging in the fields of implantology, maxillofacial surgery and orthopaedics. Current therapies such as autografts and allografts are associated with various limitations. Cytokine-based bone tissue engineering has been attracting increasing attention. Bone-inducing agents have been locally injected to stimulate the native bone-formation activity, but without much success. The reason is that these drugs must be delivered slowly and at a 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. PMID:20484228

  8. Distinct Tissue Mineral Density in Plate- and Rod-like Trabeculae of Human Trabecular Bone.

    PubMed

    Wang, Ji; Kazakia, Galateia J; Zhou, Bin; Shi, X Tony; Guo, X Edward

    2015-09-01

    Trabecular bone quality includes both microstructural and intrinsic tissue mineralization properties. However, the tissue mineralization in individual trabeculae of different trabecular types and orientations has not yet been investigated. The aim of this study was to develop an individual trabecula mineralization (ITM) analysis technique to determine tissue mineral density (TMD) distributions in plate- and rod-like trabeculae, respectively, and to compare the TMD of trabeculae along various orientations in micro-computed tomography (μCT) images of trabecular bone samples from the femoral neck, greater trochanter, and proximal tibia. ITM analyses indicated that trabecular plates, on average, had significantly higher TMD than trabecular rods. In addition, the distribution of TMD in trabecular plates depended on trabecular orientation with the lowest TMD in longitudinal plates and the highest TMD in transverse plates. Conversely, there was a relatively uniform distribution of TMD among trabecular rods, with respect to trabecular orientation. Further analyses of TMD distribution revealed that trabecular plates had higher mean and peak TMD, whereas trabecular rods had a wider TMD distribution and a larger portion of low mineralized trabeculae. Comparison of apparent Young's moduli derived from micro-finite element models with and without heterogeneous TMD demonstrated that heterogeneous TMD in trabecular plates had a significant influence on the elastic mechanical property of trabecular bone. In conclusion, this study revealed differences in TMD between plate- and rod-like trabeculae and among various trabecular orientations. The observation of less mineralized longitudinal trabecular plates suggests interesting implications of these load-bearing plates in bone remodeling. The newly developed ITM analysis can be a valuable technique to assess the influence of metabolic bone diseases and their pharmaceutical treatments on not only microstructure of trabecular bone but

  9. Microindentation for in vivo measurement of bone tissue mechanical properties in humans.

    PubMed

    Diez-Perez, Adolfo; Güerri, Roberto; Nogues, Xavier; Cáceres, Enric; Peña, Maria Jesus; Mellibovsky, Leonardo; Randall, Connor; Bridges, Daniel; Weaver, James C; Proctor, Alexander; Brimer, Davis; Koester, Kurt J; Ritchie, Robert O; Hansma, Paul K

    2010-08-01

    Bone tissue mechanical properties are deemed a key component of bone strength, but their assessment requires invasive procedures. Here we validate a new instrument, a reference point indentation (RPI) instrument, for measuring these tissue properties in vivo. The RPI instrument performs bone microindentation testing (BMT) by inserting a probe assembly through the skin covering the tibia and, after displacing periosteum, applying 20 indentation cycles at 2 Hz each with a maximum force of 11 N. We assessed 27 women with osteoporosis-related fractures and 8 controls of comparable ages. Measured total indentation distance (46.0 +/- 14 versus 31.7 +/- 3.3 microm, p = .008) and indentation distance increase (18.1 +/- 5.6 versus 12.3 +/- 2.9 microm, p = .008) were significantly greater in fracture patients than in controls. Areas under the receiver operating characteristic (ROC) curve for the two measurements were 93.1% (95% confidence interval [CI] 83.1-100) and 90.3% (95% CI 73.2-100), respectively. Interobserver coefficient of variation ranged from 8.7% to 15.5%, and the procedure was well tolerated. In a separate study of cadaveric human bone samples (n = 5), crack growth toughness and indentation distance increase correlated (r = -0.9036, p = .018), and scanning electron microscope images of cracks induced by indentation and by experimental fractures were similar. We conclude that BMT, by inducing microscopic fractures, directly measures bone mechanical properties at the tissue level. The technique is feasible for use in clinics with good reproducibility. It discriminates precisely between patients with and without fragility fracture and may provide clinicians and researchers with a direct in vivo measurement of bone tissue resistance to fracture. PMID:20200991

  10. Fractures and Biomechanical Characteristics of the Bone

    PubMed Central

    Velnar, Tomaz; Bunc, Gorazd; Gradisnik, Lidija

    2016-01-01

    The biological tissue is affected by external and internal deformation forces: tractive/tensile forces, shearing and compressive forces. The bone is deformed under the effect of a force. If the load exceeds the bone solidity limitation, fracture occurs. A mature bone consists of compact and spongy bone tissue. The basic structural unit of the cortical bone tissue are osteons and spongiosa consists of a network of bone trabeculae. The organic and mineral parts of the bone are responsible for the special bone characteristics. The effect of a physical activity on the mechanical characteristics of the bone is associated with the intensity of the load. Fractures are more common in elderly people as the bone structure is altered on account of osteoporosis and contains less bone tissue. Biomechanical characteristics with anatomic and histological bone structure as well as osteoporotic hip fractures are described in the paper. PMID:27110433

  11. A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies

    PubMed Central

    Parikh, Mukti R.; Belch, Andrew R.; Pilarski, Linda M; Kirshner, Julia

    2014-01-01

    Tissue culture has been an invaluable tool to study many aspects of cell function, from normal development to disease. Conventional cell culture methods rely on the ability of cells either to attach to a solid substratum of a tissue culture dish or to grow in suspension in liquid medium. Multiple immortal cell lines have been created and grown using such approaches, however, these methods frequently fail when primary cells need to be grown ex vivo. Such failure has been attributed to the absence of the appropriate extracellular matrix components of the tissue microenvironment from the standard systems where tissue culture plastic is used as a surface for cell growth. Extracellular matrix is an integral component of the tissue microenvironment and its presence is crucial for the maintenance of physiological functions such as cell polarization, survival, and proliferation. Here we present a 3-dimensional tissue culture method where primary bone marrow cells are grown in extracellular matrix formulated to recapitulate the microenvironment of the human bone (rBM system). Embedded in the extracellular matrix, cells are supplied with nutrients through the medium supplemented with human plasma, thus providing a comprehensive system where cell survival and proliferation can be sustained for up to 30 days while maintaining the cellular composition of the primary tissue. Using the rBM system we have successfully grown primary bone marrow cells from normal donors and patients with amyloidosis, and various hematological malignancies. The rBM system allows for direct, in-matrix real time visualization of the cell behavior and evaluation of preclinical efficacy of novel therapeutics. Moreover, cells can be isolated from the rBM and subsequently used for in vivo transplantation, cell sorting, flow cytometry, and nucleic acid and protein analysis. Taken together, the rBM method provides a reliable system for the growth of primary bone marrow cells under physiological conditions

  12. Multi-component nanofibrous scaffolds with tunable properties for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Jose, Moncy V.

    Bone is a highly complex tissue which is an integral part of vertebrates and hence any damage has a major negative effect on the quality of life. Tissue engineering is regarded as an ideal route to resolve the issues related to the scarcity of tissue and organ for transplantation. Apart from cell line and growth factors, the choice of materials and fabrication technique for scaffold are equally important. The goal of this work was to develop a multi-component nanofibrous scaffold based on a synthetic polymer (poly(lactic-co-glycolide) (PLGA)), a biopolymer (collagen) and a biomineral (nano-hydroxyapatite (nano-HA)) by electrospinning technique, which mimics the nanoscopic, chemical, and anisotropic features of bone. Preliminary studies involved fabrication of nanocomposite scaffolds based on PLGA and nano-HA. Morphological and mechanical characterizations revealed that at low concentrations, nano-HA acted as reinforcements, whereas at higher concentrations the presence of aggregation was detrimental to the scaffold. Hydrolytic degradation studies revealed the scaffold had a little mass loss and the mechanical property was maintained for a period of 6 weeks. This study was followed by evaluation of a blend system based on PLGA and collagen. Collagen addition provides hydrophilicity and the necessary cell binding sites in PLGA. The structural characterization revealed that the blend had limited interactions between the two components. The mechanical characterization revealed that with increasing collagen concentration, there was a decline in mechanical properties. However, crosslinking of the blend system, with carbodiimide (EDC) resulted in improving the mechanical properties of the scaffolds. A multi-component system was developed by adding different concentrations of nano-HA to a fixed PLGA/collagen blend composition (80/20). Morphological and mechanical characterizations revealed properties similar to the PLGA/HA system. Cyto-compatibility studies revealed

  13. Bone as a structural material: how good is it?

    PubMed

    Taylor, David

    2008-01-01

    As a structural material, bone is not very good; compared to engineering materials such as metal alloys and fibre composites, its mechanical properties are mediocre. In fact, the really amazing thing about bone is that it is able to achieve even these mediocre properties with the ingredients available: hydroxyapatite, collagen and water. Drawing on previous research, and some simple fracture mechanics calculations, we can see how bone optimises the use of these materials in a composite structure which has important features at two different scales: the nanometre scale and the hundred-micron scale. PMID:18431853

  14. Rapid prototyping: porous titanium alloy scaffolds produced by selective laser melting for bone tissue engineering.

    PubMed

    Warnke, Patrick H; Douglas, Timothy; Wollny, Patrick; Sherry, Eugene; Steiner, Martin; Galonska, Sebastian; Becker, Stephan T; Springer, Ingo N; Wiltfang, Jörg; Sivananthan, Sureshan

    2009-06-01

    Selective laser melting (SLM), a method used in the nuclear, space, and racing industries, allows the creation of customized titanium alloy scaffolds with highly defined external shape and internal structure using rapid prototyping as supporting external structures within which bone tissue can grow. Human osteoblasts were cultured on SLM-produced Ti6Al4V mesh scaffolds to demonstrate biocompatibility using scanning electron microscopy (SEM), fluorescence microscopy after cell vitality staining, and common biocompatibility tests (lactate dihydrogenase (LDH), 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), 5-bromo-2-deoxyuridine (BrdU), and water soluble tetrazolium (WST)). Cell occlusion of pores of different widths (0.45-1.2 mm) was evaluated. Scaffolds were tested for resistance to compressive force. SEM investigations showed osteoblasts with well-spread morphology and multiple contact points. Cell vitality staining and biocompatibility tests confirmed osteoblast vitality and proliferation on the scaffolds. Pore overgrowth increased during 6 weeks' culture at pore widths of 0.45 and 0.5 mm, and in the course of 3 weeks for pore widths of 0.55, 0.6, and 0.7 mm. No pore occlusion was observed on pores of width 0.9-1.2 mm. Porosity and maximum compressive load at failure increased and decreased with increasing pore width, respectively. In summary, the scaffolds are biocompatible, and pore width influences pore overgrowth, resistance to compressive force, and porosity. PMID:19072196

  15. Electrophoretic deposition of mesoporous bioactive glass on glass-ceramic foam scaffolds for bone tissue engineering.

    PubMed

    Fiorilli, Sonia; Baino, Francesco; Cauda, Valentina; Crepaldi, Marco; Vitale-Brovarone, Chiara; Demarchi, Danilo; Onida, Barbara

    2015-01-01

    In this work, the coating of 3-D foam-like glass-ceramic scaffolds with a bioactive mesoporous glass (MBG) was investigated. The starting scaffolds, based on a non-commercial silicate glass, were fabricated by the polymer sponge replica technique followed by sintering; then, electrophoretic deposition (EPD) was applied to deposit a MBG layer on the scaffold struts. EPD was also compared with other techniques (dipping and direct in situ gelation) and it was shown to lead to the most promising results. The scaffold pore structure was maintained after the MBG coating by EPD, as assessed by SEM and micro-CT. In vitro bioactivity of the scaffolds was assessed by immersion in simulated body fluid and subsequent evaluation of hydroxyapatite (HA) formation. The deposition of a MBG coating can be a smart strategy to impart bioactive properties to the scaffold, allowing the formation of nano-structured HA agglomerates within 48 h from immersion, which does not occur on uncoated scaffold surfaces. The mechanical properties of the scaffold do not vary after the EPD (compressive strength ~19 MPa, fracture energy ~1.2 × 10(6) J m(-3)) and suggest the suitability of the prepared highly bioactive constructs as bone tissue engineering implants for load-bearing applications. PMID:25578700

  16. Value and limits of μ-CT for nondemineralized bone tissue processing.

    PubMed

    Draenert, Miriam Esther; Draenert, Alice Irène; Forriol, Francisco; Cerler, Michael; Kunzelmann, Karl-Heinz; Hickel, Reinhard; Draenert, Klaus

    2012-04-01

    An experimental approach was performed on 20 giant rabbits to establish the possibilities and limitations of μ-CT for routine processing of nondemineralized bone tissue. Hydroxyapatite (HA) or β-tricalciumphosphate (β-TCP) bead implants or a melange of both, microchambered and solid, were implanted into a standardized and precise defect in the patellar groove. The bone-healing phase was chosen for the histology considering 1 or 2 days, and 2, 3, and 6 weeks. Normal X-ray and μ-CT were applied on all specimens; five specimens in the 6-week stage were additionally processed according to the full range of conventional nondemineralized bone processing methods. μ-CT increased the possibilities of nondemineralized histology with respect to bone morphometry and a complete sequence of sections, thus providing a complete analysis of the bone response. μ-CT was limited in differentiating bone quality, cell analyses, and mineralization stages. The investigation based on normal X-rays is limited to defining integration and excluding the fibrous and bony encapsulation of loose implants. μ-CT allows a 3D evaluation of newly formed bone which is clearly marked against the ceramic implant. It does not allow, however, for the differentiation between woven and lamellar bone, the presentation of the canalicular lacunar system, or on the cell level, revealing canaliculi or details of the mineralization process which can be documented by high-resolution microradiography. Titer dynamics of bone formation remains the domain of polychromatic sequential labeling. The complete sequence of μ-CT slices enhances the possibilities for routine histology, tremendously allowing to the focus on detail histology to topographically well-defined cuts, thus providing more precise conclusions which take into consideration the whole implant. PMID:22553825

  17. Mechanical evaluation of nHAp scaffold coated with poly-3-hydroxybutyrate for bone tissue engineering.

    PubMed

    Foroughi, Mohammad Reza; Karbasi, Saeed; Ebrahimi-Kahrizsangi, Reza

    2013-02-01

    Regeneration of bone, cartilage and osteochondral tissues by tissue engineering has attracted intense attention due to its potential advantages over the traditional replacement of tissues with synthetic implants. Nevertheless, there is still a dearth of ideal or suitable scaffolds based on porous biomaterials, and the present study was undertaken to develop and evaluate a useful porous composite scaffold system. In this study, nano hydroxyapatite (nHAp) powder made (about 35-45 nm) by heating at temperature of 900 degrees C and porous hydroxyapatite (40, 50 and 60 wt% solution) for making scaffold, by using Polyurethane sponge replication method. In order to increase the scaffolds mechanical properties, they coated with 2, 4 and 6 wt% Poly-3-hydroxybutyrate (P3HB) for 30 sec and 60 sec, respectively; after the scaffold coated by Polymer and survey results, this scaffold is nHAp/P3HB composite. Based on these results, this scaffold is an optimized one among three tested above mentioned composition and can be utilized in bone tissue engineering. In the result, the best of scaffold is with 50 wt% HAp and 6 wt% P3HB and porosity of present is between 80-90% with compressive strength and modulus 1.51 MPa and 22.73 MPa, respectively, that it can be application in bone tissue engineering. PMID:23646681

  18. Chitosan-collagen/organomontmorillonite scaffold for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Cao, Xianshuo; Wang, Jun; Liu, Min; Chen, Yong; Cao, Yang; Yu, Xiaolong

    2015-12-01

    A novel composite scaffold based on chitosan-collagen/organomontmorillonite (CS-COL/OMMT) was prepared to improve swelling ratio, biodegradation ratio, biomineralization and mechanical properties for use in tissue engineering applications. In order to expend the basal spacing, montmorillonite (MMT) was modified with sodium dodecyl sulfate (SDS) and was characterized by XRD, TGA and FTIR. The results indicated that the anionic surfactants entered into interlayer of MMT and the basal spacing of MMT was expanded to 3.85 nm. The prepared composite scaffolds were characterized by FTIR, XRD and SEM. The swelling ratio, biodegradation ratio and mechanical properties of composite scaffolds were also studied. The results demonstrated that the scaffold decreased swelling ratio, degradation ratio and improved mechanical and biomineralization properties because of OMMT.

  19. 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

  20. Electrospun biomimetic fibrous scaffold from shape memory polymer of PDLLA-co-TMC for bone tissue engineering.

    PubMed

    Bao, Min; Lou, Xiangxin; Zhou, Qihui; Dong, Wen; Yuan, Huihua; Zhang, Yanzhong

    2014-02-26

    Multifunctional fibrous scaffolds, which combine the capabilities of biomimicry to the native tissue architecture and shape memory effect (SME), are highly promising for the realization of functional tissue-engineered products with minimally invasive surgical implantation possibility. In this study, fibrous scaffolds of biodegradable poly(d,l-lactide-co-trimethylene carbonate) (denoted as PDLLA-co-TMC, or PLMC) with shape memory properties were fabricated by electrospinning. Morphology, thermal and mechanical properties as well as SME of the resultant fibrous structure were characterized using different techniques. And rat calvarial osteoblasts were cultured on the fibrous PLMC scaffolds to assess their suitability for bone tissue engineering. It is found that by varying the monomer ratio of DLLA:TMC from 5:5 to 9:1, fineness of the resultant PLMC fibers was attenuated from ca. 1500 down to 680 nm. This also allowed for readily modulating the glass transition temperature Tg (i.e., the switching temperature for actuating shape recovery) of the fibrous PLMC to fall between 19.2 and 44.2 °C, a temperature range relevant for biomedical applications in the human body. The PLMC fibers exhibited excellent shape memory properties with shape recovery ratios of Rr > 94% and shape fixity ratios of Rf > 98%, and macroscopically demonstrated a fast shape recovery (∼10 s at 39 °C) in the pre-deformed configurations. Biological assay results corroborated that the fibrous PLMC scaffolds were cytocompatible by supporting osteoblast adhesion and proliferation, and functionally promoted biomineralization-relevant alkaline phosphatase expression and mineral deposition. We envision the wide applicability of using the SME-capable biomimetic scaffolds for achieving enhanced efficacy in repairing various bone defects (e.g., as implants for healing bone screw holes or as barrier membranes for guided bone regeneration). PMID:24476093

  1. Dual X-Ray Absorptiometry Whole Body Composition of Bone Tissue in Rheumatoid Arthritis – a Cross-Sectional Study

    PubMed Central

    POPESCU, Claudiu; BOJINCA, Violeta; OPRIS, Daniela; IONESCU, Ruxandra

    2015-01-01

    Objectives: Previous studies of bone tissue in rheumatoid arthritis (RA) using dual X-ray absorptiometry (DXA) concentrated on regions of interest that were used to diagnose osteoporosis. This study aimed to compare the whole body bone tissue (wbBT) of RA patients with healthy subjects and to identify the RA variables which significantly predict wbBT. Methods: The study was cross-sectionally designed to include postmenopausal RA patients and age-matched healthy female controls. All 107 RA patients and all 104 controls underwent clinical examination, laboratory tests and whole body DXA composition, which recorded total and regional bone indices. Non-parametric standard statistical test and regression models after data normalization were used to assess correlations, associations and differences. Results: Compared to controls, RA patients had significantly lower whole body and regional bone mass (14.9 kg compared to 15.5 kg; p = 0.031). Disease duration (r = -0.402 ; p < 0.001), C-reactive protein (r = -0.279; p = 0.015) and inflammation (2.5% wbBT compared to 2.9%; p = 0.043), radiographic damage (14.3 kg compared to 16.2 kg; p < 0.001), disease activity scores (r = -0.275 ; p = 0.018 for HAQ) are significantly correlated/associated with lower wbBT. Clinical structural damage is associated with lower wbBT and it can significantly predict them (R2 = 0.014; p = 0.001), while glucocorticoid treatment, even in low doses, was associated with lower wbBT percent (2.6% compared to 2.8%; p = 0.045). Treatment with biologics was associated with a lower rate of whole body osteoporosis (0% compared to 22.2%; p = 0.013). Conclusions: The main associated factors with the generalized bone loss in female RA patients are disease duration and disease activity. Clinical structural damage is the most powerful predictor of the whole body bone loss. These results suggest a general disturbance of skeletal bone metabolism in RA and could explain a greater risk of fragility fractures of non

  2. Effect of FGF-2 on collagen tissue regeneration by human vertebral bone marrow stem cells.

    PubMed

    Park, Dong-Soo; Park, Jung-Chul; Lee, Jung-Seok; Kim, Tae-Wan; Kim, Ki-Joon; Jung, Byung-Joo; Shim, Eun-Kyung; Choi, Eun-Young; Park, So-Yon; Cho, Kyoo-Sung; Kim, Chang-Sung

    2015-01-15

    The effects of fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration by human bone marrow stem cells (hBMSCs) were investigated. hBMSCs were isolated from human vertebral body bone marrow during vertebral surgery and a population of hBMSCs with the characteristics of mesenchymal stem cells was observed. The FGF-2 treatment (5 ng/mL) affected on the colony-forming efficiency, proliferation, and in vitro differentiation of hBMSCs. Insoluble/soluble collagen and hydroxyproline synthesis was significantly enhanced in hBMSCs expanded with FGF-2 and the treatment of FGF-2 caused a reduction in the mRNA expression of collagen type I, but an increase of collagen types II and III along with lysyl oxidase family genes. Collagen formation was also examined using an in vivo assay model by transplanting hBMSCs into immunocompromised mice (n=4) and the histologic and immunohistochemical results revealed that significantly more collagen with a well-organized structure was formed by FGF-2-treated hBMSCs at 8 weeks posttransplantation (P<0.05). The DNA microarray assay demonstrated that genes related to extracellular matrix formation were significantly upregulated. To elucidate the underlying mechanism, chemical inhibitors against extracellular-signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) were treated and following downstream expression was observed. Collectively, FGF-2 facilitated the collagen-producing potency of hBMSCs both in vitro and in vivo, rendering them more suitable for use in collagen regeneration in the clinical field. PMID:25122057

  3. Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review

    PubMed Central

    Bose, Susmita; Tarafder, Solaiman

    2012-01-01

    Calcium phosphates (CaPs) are the most widely used bone substitutes in bone tissue engineering due to their compositional similarities to bone mineral and excellent biocompatibility. In recent years, CaPs, especially hydroxyapatite and tricalcium phosphate, have attracted significant interest in simultaneous use as bone substitute and drug delivery vehicle, adding a new dimension to their application. CaPs are more biocompatible than many other ceramic and inorganic nanoparticles. Their biocompatibility and variable stoichiometry, thus surface charge density, functionality, and dissolution properties, make them suitable for both drug and growth factor delivery. CaP matrices and scaffolds have been reported to act as delivery vehicles for growth factors and drugs in bone tissue engineering. Local drug delivery in musculoskeletal disorder treatments can address some of the critical issues more effectively and efficiently than the systemic delivery. CaPs are used as coatings on metallic implants, CaP cements, and custom designed scaffolds to treat musculoskeletal disorders. This review highlights some of the current drug and growth factor delivery approaches and critical issues using CaP particles, coatings, cements, and scaffolds towards orthopedic and dental applications. PMID:22127225

  4. Modeling of the interaction between bone tissue and resorbable biomaterial as linear elastic materials with voids

    NASA Astrophysics Data System (ADS)

    Andreaus, Ugo; Giorgio, Ivan; Madeo, Angela

    2015-02-01

    In this paper, a continuum mixture model with evolving mass densities and porosity is proposed to describe the process of bone remodeling in the presence of bio-resorbable materials as driven by externally applied loads. From a mechanical point of view, both bone tissue and biomaterial are modeled as linear elastic media with voids in the sense of Cowin and Nunziato (J Elast 13:125-147, 1983). In the proposed continuum model, the change of volume fraction related to the void volume is directly accounted for by considering porosity as an independent kinematical field. The bio-mechanical coupling is ensured by the introduction of a suitable stimulus which allows for discriminating between resorption (of both bone and biomaterial) and synthesis (of the sole natural bone) depending on the level of externally applied loads. The presence of a `lazy zone' associated with intermediate deformation levels is also considered in which neither resorption nor synthesis occur. Some numerical solutions of the integro-differential equations associated with the proposed model are provided for the two-dimensional case. Ranges of values of the parameters for which different percentages of biomaterial substitution occur are proposed, namely parameters characterizing initial and maximum values of mass densities of bone tissue and of the bio-resorbable material.

  5. Polycaprolactone scaffold engineered for sustained release of resveratrol: therapeutic enhancement in bone tissue engineering

    PubMed Central

    Kamath, Manjunath Srinivas; Ahmed, Shiek SSJ; Dhanasekaran, M; Santosh, S Winkins

    2014-01-01

    Biomaterials-based three-dimensional scaffolds are being extensively investigated in bone tissue engineering. A potential scaffold should be osteoconductive, osteoinductive, and osteogenic for enhanced bone formation. In this study, a three-dimensional porous polycapro-lactone (PCL) scaffold was engineered for prolonged release of resveratrol. Resveratrol-loaded albumin nanoparticles (RNP) were synthesized and entrapped into a PCL scaffold to form PCL-RNP by a solvent casting and leaching method. An X-ray diffraction study of RNP and PCL-RNP showed that resveratrol underwent amorphization, which is highly desired in drug delivery. Furthermore, Fourier transform infrared spectroscopy indicates that resveratrol was not chemically modified during the entrapment process. Release of resveratrol from PCL-RNP was sustained, with a cumulative release of 64% at the end of day 12. The scaffold was evaluated for its bone-forming potential in vitro using human bone marrow-derived mesenchymal stem cells for 16 days. Alkaline phosphatase activity assayed on days 8 and 12 showed a significant increase in activity (1.6-fold and 1.4-fold, respectively) induced by PCL-RNP compared with the PCL scaffold (the positive control). Moreover, von Kossa staining for calcium deposits on day 16 showed increased mineralization in PCL-RNP. These results suggest PCL-RNP significantly improves mineralization due to its controlled and prolonged release of resveratrol, thereby increasing the therapeutic potential in bone tissue engineering. PMID:24399875

  6. CONSTITUTIVE RELATIONSHIP OF TISSUE BEHAVIOR WITH DAMAGE ACCUMULATION OF HUMAN CORTICAL BONE

    PubMed Central

    Luo, Qing; Leng, Huijie; Acuna, Rae; Dong, Xuanliang; Rong, Qiguo; Wang, Xiaodu

    2010-01-01

    Microdamage accumulation has been identified as a major conduit for bone tissues to absorb fracture energy. Due to the poor understanding of its underlying mechanism, however, an adequate constitutive relationship between damage accumulation and the mechanical behavior of bone has not yet been established. In this study, the constitutive relationship between the damage accumulation induced by overload and the evolution of mechanical properties of bone with incremental deformation was established based on the experimental results obtained from a novel progressive loading protocol developed in our laboratory. First, a decayed exponential model was proposed to capture the damage accumulation (modulus loss) with increasing applied strain. Next, a power law function was proposed to represent the progression of plastic deformation with damage accumulation. Finally, a linear combination of the Kohlrausch-Williams-Watts (KWW) function and Debye function was used to depict the viscoelastic behavior of bone associated with damage accumulation. The results of this study may help develop a constitutive model for predicting the mechanical behavior of cortical bone tissues. PMID:20472239

  7. 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. PMID:25234350

  8. Polarization control of Raman spectroscopy optimizes the assessment of bone tissue

    PubMed Central

    Makowski, Alexander J.; Patil, Chetan A.; Mahadevan-Jansen, Anita

    2013-01-01

    Abstract. There is potential for Raman spectroscopy (RS) to complement tools for bone diagnosis due to its ability to assess compositional and organizational characteristics of both collagen and mineral. To aid this potential, the present study assessed specificity of RS peaks to the composition of bone, a birefringent material, for different degrees of instrument polarization. Specifically, relative changes in peaks were quantified as the incident light rotated relative to the orientation of osteonal and interstitial tissue, acquired from cadaveric femurs. In a highly polarized instrument (106∶1 extinction ratio), the most prominent mineral peak (ν1 Phosphate at 961  cm−1) displayed phase similarity with the Proline peak at 856  cm−1. This sensitivity to relative orientation between bone and light observed in the highly polarized regime persisted for certain sensitive peaks (e.g., Amide I at 1666  cm−1) in unaltered instrumentation (200∶1 extinction ratio). Though Proline intensity changed with bone rotation, the phase of Proline matched that of ν1 Phosphate. Moreover, when mapping ν1 Phosphate/Proline across osteonal-interstitial borders, the mineralization difference between the tissue types was evident whether using a 20x or 50x objectives. Thus, the polarization bias inherent in commercial RS systems does not preclude the assessment of bone composition when using phase-matched peaks. PMID:23708192

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

    PubMed

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

    2015-08-01

    Bone tissue engineering aims to overcome the drawbacks of current bone regeneration techniques in orthopaedics. Bioreactors are widely used in the field of bone tissue engineering, as they help support efficient nutrition of cultured cells with the possible combination of applying mechanical stimuli. Beneficial influencing parameters of in vitro cultures are difficult to find and are mostly determined by trial and error, which is associated with significant time and money spent. Mathematical simulations can support the finding of optimal parameters. Simulations have evolved over the last 20 years from simple analytical models to complex and detailed computational models. They allow researchers to simulate the mechanical as well as the biological environment experienced by cells seeded on scaffolds in a bioreactor. Based on the simulation results, it is possible to give recommendations about specific parameters for bone bioreactor cultures, such as scaffold geometries, scaffold mechanical properties, the level of applied mechanical loading or nutrient concentrations. This article reviews the evolution in simulating various aspects of dynamic bone culture in bioreactors and reveals future research directions. PMID:23625691

  10. Development of bone and cartilage in tissue-engineered human middle phalanx models.

    PubMed

    Wada, Yoshitaka; Enjo, Mitsuhiro; Isogai, Noritaka; Jacquet, Robin; Lowder, Elizabeth; Landis, William J

    2009-12-01

    Human middle phalanges were tissue-engineered with midshaft scaffolds of poly(L-lactide-epsilon-caprolactone) [P(LA-CL)], hydroxyapatite-P(LA-CL), or beta-tricalcium phosphate-P(LA-CL) and end plate scaffolds of bovine chondrocyte-seeded polyglycolic acid. Midshafts were either wrapped with bovine periosteum or left uncovered. Constructs implanted in nude mice for up to 20 weeks were examined for cartilage and bone development as well as gene expression and protein secretion, which are important in extracellular matrix (ECM) formation and mineralization. Harvested 10- and 20-week constructs without periosteum maintained end plate cartilage but no growth plate formation. They also consisted of chondrocytes secreting type II collagen and proteoglycan, and they were composed of midshaft regions devoid of bone. In all periosteum-wrapped constructs at like times, end plate scaffolds held chondrocytes elaborating type II collagen and proteoglycan and cartilage growth plates resembling normal tissue. Chondrocyte gene expression of type II collagen, aggrecan, and bone sialoprotein varied depending on midshaft composition, presence of periosteum, and length of implantation time. Periosteum produced additional cells, ECM, and mineral formation within the different midshaft scaffolds. Periosteum thus induces midshaft development and mediates chondrocyte gene expression and growth plate formation in cartilage regions of phalanges. This work is important for understanding developmental principles of tissue-engineered phalanges and by extension those of normal growth plate cartilage and bone. PMID:19527181

  11. Development of Bone and Cartilage in Tissue-Engineered Human Middle Phalanx Models

    PubMed Central

    Wada, Yoshitaka; Enjo, Mitsuhiro; Isogai, Noritaka; Jacquet, Robin; Lowder, Elizabeth

    2009-01-01

    Human middle phalanges were tissue-engineered with midshaft scaffolds of poly(L-lactide-ɛ-caprolactone) [P(LA-CL)], hydroxyapatite-P(LA-CL), or β-tricalcium phosphate-P(LA-CL) and end plate scaffolds of bovine chondrocyte-seeded polyglycolic acid. Midshafts were either wrapped with bovine periosteum or left uncovered. Constructs implanted in nude mice for up to 20 weeks were examined for cartilage and bone development as well as gene expression and protein secretion, which are important in extracellular matrix (ECM) formation and mineralization. Harvested 10- and 20-week constructs without periosteum maintained end plate cartilage but no growth plate formation. They also consisted of chondrocytes secreting type II collagen and proteoglycan, and they were composed of midshaft regions devoid of bone. In all periosteum-wrapped constructs at like times, end plate scaffolds held chondrocytes elaborating type II collagen and proteoglycan and cartilage growth plates resembling normal tissue. Chondrocyte gene expression of type II collagen, aggrecan, and bone sialoprotein varied depending on midshaft composition, presence of periosteum, and length of implantation time. Periosteum produced additional cells, ECM, and mineral formation within the different midshaft scaffolds. Periosteum thus induces midshaft development and mediates chondrocyte gene expression and growth plate formation in cartilage regions of phalanges. This work is important for understanding developmental principles of tissue-engineered phalanges and by extension those of normal growth plate cartilage and bone. PMID:19527181

  12. 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

  13. Conversion of natural marine skeletons as scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Zhang, Xing; Vecchio, Kenneth S.

    2013-06-01

    Marine CaCO3 skeletons have tailored architectures created by nature, which give them structural support and other functions. For example, seashells have dense lamellar structures, while coral, cuttlebone and sea urchin spines have interconnected porous structures. In our experiments, seashells, coral and cuttlebone were hydrothermally converted to hydroxyapatite (HAP), and sea urchin spines were converted to Mg-substituted tricalcium phosphate, while maintaining their original structures. Partially converted shell samples have mechanical strength, which is close to that of compact human bone. After implantation of converted shell and spine samples in rat femoral defects for 6 weeks, there was newly formed bone growth up to and around the implants. Some new bone was found to migrate through the pores of converted spine samples and grow inward. These results show good bioactivity and osteoconductivity of the implants, indicating the converted shell and spine samples can be used as bone defect fillers. The interconnected porous HAP scaffolds from converted coral or cuttlebone that have pore size larger than 100 ?m likely support infiltration of bone cells and vessels, and finally encourage new bone ingrowth.

  14. The 3D structure of the collagen fibril network in human trabecular bone: relation to trabecular organization.

    PubMed

    Reznikov, Natalie; Chase, Hila; Brumfeld, Vlad; Shahar, Ron; Weiner, Steve

    2015-02-01

    Trabecular bone is morphologically and functionally different from compact bone at the tissue level, but both are composed of lamellae at the micrometer-scale level. We present a three-dimensional study of the collagenous network of human trabecular lamellar bone from the proximal femur using the FIB-SEM serial surface view method. The results are compared to human compact lamellar bone of the femoral shaft, studied by the same method. Both demineralized trabecular and compact lamellar bone display the same overall structural organization, namely the presence of ordered and disordered materials and the confinement of the canalicular network to the disordered material. However, in trabecular bone lamellae a significant proportion of the ordered collagen fibril arrays is aligned with the long axis of the trabecula and, unlike in compact bone, is not related to the anatomical axis of the whole femur. The remaining ordered collagen fibrils are offset from the axis of a trabecula either by about 30° or 70°. Interestingly, at the tissue scale of millimeters, the most abundant angles between any two connected trabeculae - the inter-trabecular angles - center around 30° and 70°. This implies that within a framework of interconnected trabeculae the same lamellar structure will always have a significant component of the fibrils aligned with the long axes of connected trabeculae. This structural complementarity at different hierarchical levels presumably reflects an adaptation of trabecular bone to function. PMID:25445457

  15. [Characteristics of bone tissue of rats after flight aboard biosputnik Kosmos-1129].

    PubMed

    Rogacheva, I V; Stupakov, G P; Volozhin, A I; Pavlova, M N; Poliakov, A N

    1984-01-01

    Bones of rats flown for 19 days onboard Cosmos-1129 were examined. The examination included bone mass, density, mineral composition, reconstruction parameters, and elemental composition at R + 1, R + 6, and R + 29. After flight the rats developed osteoporosis in the spongy structures of tubular bones and a smaller thickness of the cortical layer of the diaphysis; they showed no mineralization of the microstructures, a slight decrease of the Ca concentration, and a normal content of P. At R + 6 these changes progressively developed and at R + 29 they returned to normal. PMID:6513471

  16. A Mechanobiology-based Algorithm to Optimize the Microstructure Geometry of Bone Tissue Scaffolds

    PubMed Central

    Boccaccio, Antonio; Uva, Antonio Emmanuele; Fiorentino, Michele; Lamberti, Luciano; Monno, Giuseppe

    2016-01-01

    Complexity of scaffold geometries and biological mechanisms involved in the bone generation process make the design of scaffolds a quite challenging task. The most common approaches utilized in bone tissue engineering require costly protocols and time-consuming experiments. In this study we present an algorithm that, combining parametric finite element models of scaffolds with numerical optimization methods and a computational mechano-regulation model, is able to predict the optimal scaffold microstructure. The scaffold geometrical parameters are perturbed until the best geometry that allows the largest amounts of bone to be generated, is reached. We study the effects of the following factors: (1) the shape of the pores; (2) their spatial distribution; (3) the number of pores per unit area. The optimal dimensions of the pores have been determined for different values of scaffold Young's modulus and compression loading acting on the scaffold upper surface. Pores with rectangular section were predicted to lead to the formation of larger amounts of bone compared to square section pores; similarly, elliptic pores were predicted to allow the generation of greater amounts of bone compared to circular pores. The number of pores per unit area appears to have rather negligible effects on the bone regeneration process. Finally, the algorithm predicts that for increasing loads, increasing values of the scaffold Young's modulus are preferable. The results shown in the article represent a proof-of-principle demonstration of the possibility to optimize the scaffold microstructure geometry based on mechanobiological criteria. PMID:26722213

  17. Strategies to Stimulate Mobilization and Homing of Endogenous Stem and Progenitor Cells for Bone Tissue Repair

    PubMed Central

    Herrmann, Marietta; Verrier, Sophie; Alini, Mauro

    2015-01-01

    The gold standard for the treatment of critical-size bone defects is autologous or allogenic bone graft. This has several limitations including donor site morbidity and the restricted supply of graft material. Cell-based tissue engineering strategies represent an alternative approach. Mesenchymal stem cells (MSCs) have been considered as a source of osteoprogenitor cells. More recently, focus has been placed on the use of endothelial progenitor cells (EPCs), since vascularization is a critical step in bone healing. Although many of these approaches have demonstrated effectiveness for bone regeneration, cell-based therapies require time consuming and cost-expensive in vitro cell expansion procedures. Accordingly, research is becoming increasingly focused on the homing and stimulation of native cells. The stromal cell-derived factor-1 (SDF-1) – CXCR4 axis has been shown to be critical for the recruitment of MSCs and EPCs. Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and has been targeted in many studies. Here, we present an overview of the different approaches for delivering homing factors to the defect site by absorption or incorporation to biomaterials, gene therapy, or via genetically manipulated cells. We further review strategies focusing on the stimulation of endogenous cells to support bone repair. Finally, we discuss the major challenges in the treatment of critical-size bone defects and fracture non-unions. PMID:26082926

  18. Multiple soft tissue aneurysmal cysts: An occurrence after resection of primary aneurysmal bone cyst of fibula

    PubMed Central

    Karkuzhali, P; Bhattacharyya, Mahuya; Sumitha, P

    2007-01-01

    We report a case of multiple extraosseous aneurysmal cysts occurring in the muscle and subcutaneous plane of postero-lateral aspects of the upper right leg. They appeared about 15 months after resection of aneurysmal bone cyst of the upper end of the fibula. They varied in size from 2 cm to 5 cm. Radiologically they were well-defined lesions with central septate areas surrounded by a rim of calcification. Histologically they showed central cystic spaces separated by septa consisting of fibroblasts, osteoclast type of giant cells and reactive woven bone. Thus they showed histological similarity with aneurysmal bone cysts, but did not show any connection with the bone. Only very few examples of aneurysmal cysts of soft tissue had been described in the past one decade and they were reported in various locations including rare sites such as arterial wall and larynx. Recent cytogenetic analyses have shown abnormalities involving 17p11-13 and/or 16q22 in both osseous and extraosseous aneurysmal cysts indicating its probable neoplastic nature. Our case had unique features like multiplicity and occurrence after resection of primary aneurysmal bone cyst of the underlying bone. PMID:21139755

  19. Bioactive glass scaffolds for bone tissue engineering: state of the art and future perspectives

    PubMed Central

    Fu, Qiang; Saiz, Eduardo; Rahaman, Mohamed N.; Tomsia, Antoni P.

    2011-01-01

    The repair and regeneration of large bone defects resulting from disease or trauma remains a significant clinical challenge. Bioactive glass has appealing characteristics as a scaffold material for bone tissue engineering, but the application of glass scaffolds for the repair of load-bearing bone defects is often limited by their low mechanical strength and fracture toughness. This paper provides an overview of recent developments in the fabrication and mechanical properties of bioactive glass scaffolds. The review reveals the fact that mechanical strength is not a real limiting factor in the use of bioactive glass scaffolds for bone repair, an observation not often recognized by most researchers and clinicians. Scaffolds with compressive strengths comparable to those of trabecular and cortical bones have been produced by a variety of methods. The current limitations of bioactive glass scaffolds include their low fracture toughness (low resistance to fracture) and limited mechanical reliability, which have so far received little attention. Future research directions should include the development of strong and tough bioactive glass scaffolds, and their evaluation in unloaded and load-bearing bone defects in animal models. PMID:21912447

  20. A Mechanobiology-based Algorithm to Optimize the Microstructure Geometry of Bone Tissue Scaffolds.

    PubMed

    Boccaccio, Antonio; Uva, Antonio Emmanuele; Fiorentino, Michele; Lamberti, Luciano; Monno, Giuseppe

    2016-01-01

    Complexity of scaffold geometries and biological mechanisms involved in the bone generation process make the design of scaffolds a quite challenging task. The most common approaches utilized in bone tissue engineering require costly protocols and time-consuming experiments. In this study we present an algorithm that, combining parametric finite element models of scaffolds with numerical optimization methods and a computational mechano-regulation model, is able to predict the optimal scaffold microstructure. The scaffold geometrical parameters are perturbed until the best geometry that allows the largest amounts of bone to be generated, is reached. We study the effects of the following factors: (1) the shape of the pores; (2) their spatial distribution; (3) the number of pores per unit area. The optimal dimensions of the pores have been determined for different values of scaffold Young's modulus and compression loading acting on the scaffold upper surface. Pores with rectangular section were predicted to lead to the formation of larger amounts of bone compared to square section pores; similarly, elliptic pores were predicted to allow the generation of greater amounts of bone compared to circular pores. The number of pores per unit area appears to have rather negligible effects on the bone regeneration process. Finally, the algorithm predicts that for increasing loads, increasing values of the scaffold Young's modulus are preferable. The results shown in the article represent a proof-of-principle demonstration of the possibility to optimize the scaffold microstructure geometry based on mechanobiological criteria. PMID:26722213

  1. Design of an Osteoinductive Extracellular Fibronectin Matrix Protein for Bone Tissue Engineering

    PubMed Central

    Lee, Sujin; Lee, Dong-Sung; Choi, Ilsan; Pham, Le B. Hang; Jang, Jun-Hyeog

    2015-01-01

    Integrin-mediated cell-matrix interactions play an important role in osteogenesis. Here, we constructed a novel osteoinductive fibronectin matrix protein (oFN) for bone tissue engineering, designed to combine the integrin-binding modules from fibronectin (iFN) and a strong osteoinductive growth factor, bone morphogenetic protein-2. Compared with iFN, the purified oFN matrix protein caused a significant increase in cell adhesion and osteogenic differentiation of pre-osteoblast MC3T3-E1 cells (p < 0.05). PMID:25853265

  2. Neutron activation analysis of NBS oyster tissue (SRM 1566) and IAEA animal bone (H-5)

    SciTech Connect

    Lepel, E.A.; Laul, J.C.

    1984-03-01

    Instrumental and radiochemical neutron activation analysis (INAA and RNAA) were employed to measure about 37 major, minor, and trace elements in two standard reference materials: oyster tissue (SRM 1566) supplied by the National Bureau of Standards (NBS) and animal bone (H-5) supplied by the International Atomic Energy Agency (IAEA). Wherever the comparison exists, our data show excellent agreement with accepted values for each SRM. These SRM's are useful as reference standards for the analysis of biological materials. Additionally, the chondritic normalized rare earth element pattern of animal bone behaves as a smooth function of the ionic radii, as previously observed for biological materials.

  3. Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues

    PubMed Central

    Nichols, Scott P.; Storm, Wesley L.; Koh, Ahyeon; Schoenfisch, Mark H.

    2012-01-01

    Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair. PMID:22433782

  4. Spectroscopic characterization of bone tissue of experimental animals after glucocorticoid treatment and recovery period

    NASA Astrophysics Data System (ADS)

    Mitić, Žarko J.; Najman, Stevo J.; Cakić, Milorad D.; Ajduković, Zorica R.; Ignjatović, Nenad L.; Nikolić, Ružica S.; Nikolić, Goran M.; Stojanović, Sanja T.; Vukelić, Marija Đ.; Trajanović, Miroslav D.

    2014-09-01

    The influence of glucocorticoids on the composition and mineral/organic content of the mandible in tested animals after recovery and healing phase was investigated in this work. The results of FTIR analysis demonstrated that bone tissue composition was changed after glucocorticoid treatment. The increase of calcium, magnesium, phosphorus content and mineral part of bones was statistically significant in recovery phase and in treatment phase that included calcitonin and thymus extract. Some changes also happened in the organic part of the matrix, as indicated by intensity changes for already present IR bands and the appearance of new IR bands in the region 3500-1300 cm-1.

  5. Wound healing after irradiation of bone tissues by Er:YAG laser

    NASA Astrophysics Data System (ADS)

    Watanabe, Hisashi; Yoshino, Toshiaki; Aoki, Akira; Ishikawa, Isao

    1997-05-01

    Clinical applications of Er:YAG laser are now developing in periodontics and restorative dentistry. To date, there have been few studies indicating safety criteria for intraoral usage of the Er:YAG laser. The present study examined the effects of the Er:YAG laser on bone tissues, supposing mis- irradiation in the oral cavity during dental application, especially periodontal surgery. The experiments were performed using the newly-developed Er:YAG laser apparatus equipped with a contact probe. In experiment 1, 10 pulses of laser irradiation were administered to the parietal bone of a rat at 50, 150 and 300 mJ/pulse with and without water irrigation, changing the irradiation distance to 0, 5, 10 and 20 mm, respectively. As a control, electric knife was employed. Macroscopic and SEM observations of the wound surface were performed. In experiment 2, laser irradiation in a straight line was performed at 150 mJ/pulse, 1- pps and 0,5, 10 mm irradiation distance without water irrigation. Wound healing was observed histologically at 0, 3, 7, 14 and 28 days after laser irradiation and compared with that of the control. Non-contact irradiation by Er:YAG laser did not cause severe damage to the parietal bone tissue under water irrigation. Contact irradiation induced a limited wound, however, new bone formation was observed 28 days after laser irradiation, while osseous defect with thermal degenerative tissue remained at the control site. In conclusion, irradiation with an Er:YAG laser would not cause severe damage to surrounding bone tissues in the oral cavity when used within the usual power settings for dental treatment. Furthermore, this laser may be applicable for osseous surgery because of its high ablation efficiency and good wound healing after irradiation.

  6. In Vitro Corrosion and Cytocompatibility Properties of Nano-Whisker Hydroxyapatite Coating on Magnesium Alloy for Bone Tissue Engineering Applications

    PubMed Central

    Yang, Huawei; Yan, Xueyu; Ling, Min; Xiong, Zuquan; Ou, Caiwen; Lu, Wei

    2015-01-01

    We report here the successful fabrication of nano-whisker hydroxyapatite (nHA) coatings on Mg alloy by using a simple one-step hydrothermal process in aqueous solution. The nHA coating shows uniform structure and high crystallinity. Results indicate that nHA coating is promising for improving the in vitro corrosion and cytocompatibility properties of Mg-based implants and devices for bone tissue engineering. In addition, the simple hydrothermal deposition method used in the current study is also applicable to substrates with complex shapes or surface geometries. PMID:25789500

  7. Human Bone Marrow Stromal Cells: A Reliable, Challenging Tool for In Vitro Osteogenesis and Bone Tissue Engineering Approaches

    PubMed Central

    Hempel, Ute; Müller, Katrin; Preissler, Carolin; Noack, Carolin; Boxberger, Sabine; Dieter, Peter; Bornhäuser, Martin; Wobus, Manja

    2016-01-01

    Adult human bone marrow stromal cells (hBMSC) are important for many scientific purposes because of their multipotency, availability, and relatively easy handling. They are frequently used to study osteogenesis in vitro. Most commonly, hBMSC are isolated from bone marrow aspirates collected in clinical routine and cultured under the “aspect plastic adherence” without any further selection. Owing to the random donor population, they show a broad heterogeneity. Here, the osteogenic differentiation potential of 531 hBMSC was analyzed. The data were supplied to correlation analysis involving donor age, gender, and body mass index. hBMSC preparations were characterized as follows: (a) how many passages the osteogenic characteristics are stable in and (b) the influence of supplements and culture duration on osteogenic parameters (tissue nonspecific alkaline phosphatase (TNAP), octamer binding transcription factor 4, core-binding factor alpha-1, parathyroid hormone receptor, bone gla protein, and peroxisome proliferator-activated protein γ). The results show that no strong prediction could be made from donor data to the osteogenic differentiation potential; only the ratio of induced TNAP to endogenous TNAP could be a reliable criterion. The results give evidence that hBMSC cultures are stable until passage 7 without substantial loss of differentiation potential and that established differentiation protocols lead to osteoblast-like cells but not to fully authentic osteoblasts. PMID:27293446

  8. Cultivation of Human Bone-Like Tissue from Pluripotent Stem Cell-Derived Osteogenic Progenitors in Perfusion Bioreactors

    PubMed Central

    de Peppo, Giuseppe Maria; Vunjak-Novakovic, Gordana; Marolt, Darja

    2014-01-01

    Human pluripotent stem cells represent an unlimited source of skeletal tissue progenitors for studies of bone biology, pathogenesis, and the development of new approaches for bone reconstruction and therapies. In order to construct in vitro models of bone tissue development and to grow functional, clinical-size bone substitutes for transplantation, cell cultivation in three-dimensional environments composed of porous osteoconductive scaffolds and dynamic culture systems—bioreactors—has been studied. Here, we describe a stepwise procedure for the induction of human embryonic and induced pluripotent stem cells (collectively termed PSCs) into mesenchymal-like progenitors, and their subsequent cultivation on decellularized bovine bone scaffolds in perfusion bioreactors, to support the development of viable, stable bone-like tissue in defined geometries. PMID:24281874

  9. Fabrication of cancellous biomimetic chitosan-based nanocomposite scaffolds applying a combinational method for bone tissue engineering.

    PubMed

    Jamalpoor, Zahra; Mirzadeh, Hamid; Joghataei, Mohammad Taghi; Zeini, Darya; Bagheri-Khoulenjani, Shadab; Nourani, Mohammad Reza

    2015-05-01

    The aim of this study was to mimic the specific structure of bone and fabricate a biomimetic nano-hydroxyapatite (HA)/chitosan (Cs)/gelatin scaffolds using combination of particle leaching and freeze drying methods eliminating mold effects. To achieve an optimum structure, scaffolds with different gelatin/Cs weight ratio were fabricated. Morphological characterization of scaffolds by scanning electron microscopy method showed highly interconnected porous structures similar to cancellous bone with mean pore size ranging from 140 to 190 μm. Nano-HA crystals were dispersed homogeneously in the polymer matrix according to the energy-dispersive X-ray spectroscopy and transmission electron microscopy images. Fourier transform infrared and X-ray diffraction results disclosed that chemical interactions were formed between nano-HA, Cs, gelatin and crystallinity of each material decreased with blending. It was found that increasing the gelatin content significantly improved water uptake, degradation rate as well as attachment, infiltration and proliferation of Saos2 cells to the scaffolds. The presented results confirm that the designed biomimetic nano-HA /Cs/gelatin scaffolds can be used as promising substitutes for bone tissue engineering. PMID:25195588

  10. 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 re