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Sample records for bone tissue structure

  1. 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

  2. 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

  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

    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.

  5. 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.

  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

    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 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

  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 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

  18. 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

  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

    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 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

  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. 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

  18. 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

  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. 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

  12. 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

  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. 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

  15. 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

  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, 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.

  10. 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.

  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. 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.

  6. 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

  7. 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.

  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. 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

  12. 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

  13. 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

  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. 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

  20. 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

  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. 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

  7. 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.

  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. 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

  12. 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.

  13. 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

  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. 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

  20. 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.

  1. 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

  2. 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.

  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. 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

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

    NASA Astrophysics Data System (ADS)

    Mehr, Nima Ghavidel

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

  8. 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. 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

  10. 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

  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. 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

  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. 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

  6. 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.

  7. 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

  8. 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

  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