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Sample records for bone potential applications

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

    PubMed

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

    2014-01-01

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

  2. Wnt signaling and potential applications in bone diseases.

    PubMed

    Rawadi, Georges

    2008-07-01

    In the United States, it is estimated that $10-15 billion is spent annually for the treatment of osteoporotic fracture. The worldwide annual incidence of osteoporotic hip fracture exceeds 1.7 million cases. Bone loss leading to osteoporosis and osteoporotic fractures are caused by an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption and numerous factors have been implicated in the development of osteoporosis. The prevention and treatment of osteoporosis traditionally involves the use of anti-resorptive agents, which target osteoclast function, but do not lead to a significant increase in bone mass and therefore only partially reduce risk of fractures. For these reasons, the search for anabolic agents, which target osteoblast function, represents an urgent medical need. Genetic studies have firmly established a link between bone mass in humans and Wnt signaling. Multiple genetic and pharmacological manipulations of Wnt signaling in mice have since then confirmed the central role of this pathway in regulating bone formation. The existence of many potential pharmacological targets in this pathway makes it attractive for bone anabolic drug discovery.

  3. Bone marrow stromal stem cells: nature, biology, and potential applications.

    PubMed

    Bianco, P; Riminucci, M; Gronthos, S; Robey, P G

    2001-01-01

    Bone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes. In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use. Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy.

  4. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

    PubMed

    Saito, Takafumi; Okumoto, Kazuo; Haga, Hiroaki; Nishise, Yuko; Ishii, Rika; Sato, Chikako; Watanabe, Hisayoshi; Okada, Akio; Ikeda, Motoki; Togashi, Hitoshi; Ishikawa, Tsuyoshi; Terai, Shuji; Sakaida, Isao; Kawata, Sumio

    2011-09-01

    The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

  5. Biomimetic chitosan-calcium phosphate composites with potential applications as bone substitutes: preparation and characterization.

    PubMed

    Tanase, Constantin E; Popa, Marcel I; Verestiuc, Liliana

    2012-04-01

    A novel biomimetic technique for obtaining chitosan-calcium phosphates (Cs-CP) scaffolds are presented: calcium phosphates are precipitated from its precursors, CaCl(2) and NaH(2) PO(4) on the Cs matrix, under physiological conditions (human body temperature and body fluid pH; 37°C and pH = 7.2, respectively). Materials composition and structure have been confirmed by various techniques: elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM). FTIR and SEM data have shown the arrangement of the calcium phosphates-hydroxyapatite (CP-Hap) onto Cs matrix. In this case the polymer is acting as glue, bonding the calcium phosphates crystals. Behavior in biological simulated fluids (phosphate buffer solution-PBS and PBS-albumin) revealed an important contribution of the chelation between -NH3(+) and Ca(2+) on the scaffold interaction with aqueous mediums; increased quantities of chitosan in composites permit the interaction with human albumin and improve the retention of fluid. The composites are slightly degraded by the lysozyme which facilitates an in vivo degradation control of bone substitutes. Modulus of elasticity is strongly dependent of the ratio chitosan/calcium phosphates and recommends the obtained biomimetic composites as promising materials for a prospective bone application.

  6. Development of Novel Biocomposite Scaffold of Chitosan-Gelatin/Nanohydroxyapatite for Potential Bone Tissue Engineering Applications

    NASA Astrophysics Data System (ADS)

    Dan, Yang; Liu, Ouyang; Liu, Yong; Zhang, Yuan-Yuan; Li, Shuai; Feng, Xiao-bo; Shao, Zeng-wu; Yang, Cao; Yang, Shu-Hua; Hong, Ji-bo

    2016-11-01

    In this study, a three-dimensional chitosan-gelatin/nanohydroxyapatite (ChG/nHaP) scaffold was successfully fabricated and characterized in terms of swelling, degradation, cell proliferation, cell attachment, and mineralization characterizations. The ChG/nHaP scaffold was fabricated with a mean pore size of 100-180 μm. Our results showed that the physicochemical and biological properties of the scaffolds were affected by the presence of HaP. The swelling and degradation characteristics of the ChG scaffold were remarkably decreased by the addition of HaP. On the other hand, the presence of HaP remarkably improved the MC3T3-E1 cell attachment and cell growth in the scaffold membrane. The biocompatible nature of the ChG/nHaP scaffold leads to the development of finely scaled mineral deposits on the scaffold membrane. Thus, HaP played an important role in improving the biological performance of the scaffold. Therefore, the ChG/nHaP scaffold could be applied as a suitable material for bone tissue engineering applications.

  7. 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.

  8. Potential of Bone Marrow Stromal Cells in Applications for Neuro-Degenerative, Neuro-Traumatic and Muscle Degenerative Diseases

    PubMed Central

    Dezawa, Mari; Ishikawa, Hiroto; Hoshino, Mikio; Itokazu, Yutaka; Nabeshima, Yo-ichi

    2005-01-01

    Cell transplantation is a promising strategy for the treatment of neurodegenerative and muscle degenerative diseases. Many kinds of cells, including embryonic stem cells and tissue stem cells, have been considered as candidates for transplantation therapy. Bone marrow stromal cells (MSCs) have great potential as therapeutic agents since they are easy to isolate and can be expanded from patients without serious ethical or technical problems. We discovered a new method for the highly efficient and specific induction of functional Schwann cells, neurons and skeletal muscle lineage cells from both rat and human MSCs. These induced cells were transplanted into animal models of neurotraumatic injuries, Parkinson’s disease, stroke and muscle dystrophies, resulting in the successful integration of transplanted cells and an improvement in behavior of the transplanted animals. Here we focus on the respective potentials of MSC-derived cells and discuss the possibility of clinical application in degenerative diseases. PMID:18369401

  9. Development of model hydroxyapatite bone scaffolds with multiscale porosity for potential load bearing applications

    NASA Astrophysics Data System (ADS)

    Dellinger, Jennifer Gwynne

    2005-11-01

    Model hydroxyapatite (HA) bone scaffolds consisting of a latticed pattern of rods were fabricated by a solid freeform fabrication (SFF) technique based on the robotic deposition of colloidal pastes. An optimal HA paste formulation for this method was developed. Local porosity, i.e. microporosity (1--30 mum) and sintering porosity (less than 1 mum), were produced by including polymer microsphere porogens in the HA pastes and by controlling the sintering of the scaffolds. Scaffolds with and without local porosity were evaluated with and without in vitro accelerated degradation. Percent weight loss of the scaffolds and calcium and phosphorus concentrations in solution increased with degradation time. After degradation, compressive strength and modulus decreased significantly for scaffolds with local porosity, but did not change significantly for scaffolds without local porosity. The compressive strength and modulus of scaffolds without local porosity were comparable to human cortical bone and were significantly greater than the scaffolds with local porosity. Micropores in HA disks caused surface pits that increased the surface roughness as compared to non-microporous HA disks. Mouse mesenchymal stem cells extended their cell processes into these microporous pits on HA disks in vitro. ALP expression was prolonged, cell attachment strength increased, and ECM production appeared greater on microporous HA disks compared to non-microporous HA disks and tissue culture treated polystyrene controls. Scaffolds with and without microporosity were implanted in goats bones. Microporous scaffolds with rhBMP-2 increased the percent of the scaffold filled with bone tissue compared to microporous scaffolds without rhBMP-2. Lamellar bone inside scaffolds was aligned near the rods junctions whereas lamellar bone was aligned in a more random configuration away from the rod junctions. Microporous scaffolds stained darkly with toluidine blue beneath areas of contact with new bone. This

  10. Silver nanoparticle based antibacterial methacrylate hydrogels potential for bone graft applications.

    PubMed

    González-Sánchez, M Isabel; Perni, Stefano; Tommasi, Giacomo; Morris, Nathanael Glyn; Hawkins, Karl; López-Cabarcos, Enrique; Prokopovich, Polina

    2015-05-01

    Infections are frequent and very undesired occurrences after orthopedic procedures; furthermore, the growing concern caused by the rise in antibiotic resistance is progressively dwindling the efficacy of such drugs. Artificial bone graft materials could solve some of the problems associated with the gold standard use of natural bone graft such as limited bone material, pain at the donor site and rejections if donor tissue is used. We have previously described new acrylate base nanocomposite hydrogels as bone graft materials. In the present paper, we describe the integration of silver nanoparticles in the polymeric mineralized biomaterial to provide non-antibiotic antibacterial activity against Staphylococcus epidermidis and Methicillin-resistant Staphylococcus aureus. Two different crosslinking degrees were tested and the silver nanoparticles were integrated into the composite matrix by means of three different methods: entrapment in the polymeric hydrogel before the mineralization; diffusion during the process of calcium phosphate crystallization and adsorption post-mineralization. The latter being generally the most effective method of encapsulation; however, the adsorption of silver nanoparticles inside the pores of the biomaterial led to a decreasing antibacterial activity for adsorption time longer than 2 days.

  11. Silver nanoparticle based antibacterial methacrylate hydrogels potential for bone graft applications

    PubMed Central

    González-Sánchez, M. Isabel; Perni, Stefano; Tommasi, Giacomo; Morris, Nathanael Glyn; Hawkins, Karl; López-Cabarcos, Enrique; Prokopovich, Polina

    2015-01-01

    Infections are frequent and very undesired occurrences after orthopedic procedures; furthermore, the growing concern caused by the rise in antibiotic resistance is progressively dwindling the efficacy of such drugs. Artificial bone graft materials could solve some of the problems associated with the gold standard use of natural bone graft such as limited bone material, pain at the donor site and rejections if donor tissue is used. We have previously described new acrylate base nanocomposite hydrogels as bone graft materials. In the present paper, we describe the integration of silver nanoparticles in the polymeric mineralized biomaterial to provide non-antibiotic antibacterial activity against Staphylococcus epidermidis and Methicillin-resistant Staphylococcus aureus. Two different crosslinking degrees were tested and the silver nanoparticles were integrated into the composite matrix by means of three different methods: entrapment in the polymeric hydrogel before the mineralization; diffusion during the process of calcium phosphate crystallization and adsorption post-mineralization. The latter being generally the most effective method of encapsulation; however, the adsorption of silver nanoparticles inside the pores of the biomaterial led to a decreasing antibacterial activity for adsorption time longer than 2 days. PMID:25746278

  12. Tailoring the degradation and biological response of a magnesium-strontium alloy for potential bone substitute application.

    PubMed

    Han, Junjie; Wan, Peng; Ge, Ye; Fan, Xinmin; Tan, Lili; Li, Jianjun; Yang, Ke

    2016-01-01

    Bone defects are very challenging in orthopedic practice. There are many practical and clinical shortcomings in the repair of the defect by using autografts, allografts or xenografts, which continue to motivate the search for better alternatives. The ideal bone grafts should provide mechanical support, fill osseous voids and enhance the bone healing. Biodegradable magnesium-strontium (Mg-Sr) alloys demonstrate good biocompatibility and osteoconductive properties, which are promising biomaterials for bone substitutes. The aim of this study was to evaluate and pair the degradation of Mg-Sr alloys for grafting with their clinical demands. The microstructure and performance of Mg-Sr alloys, in vitro degradation and biological properties including in vitro cytocompatibility and in vivo implantation were investigated. The results showed that the as-cast Mg-Sr alloy exhibited a rapid degradation rate compared with the as-extruded alloy due to the intergranular distribution of the second phase and micro-galvanic corrosion. However, the initial degradation could be tailored by the coating protection, which was proved to be cytocompatible and also suitable for bone repair observed by in vivo implantation. The integrated fracture calluses were formed and bridged the fracture gap without gas bubble accumulation, meanwhile the substitutes simultaneously degraded. In conclusion, the as-cast Mg-Sr alloy with coating is potential to be used for bone substitute alternative.

  13. Prostaglandin E2: from clinical applications to its potential role in bone- muscle crosstalk and myogenic differentiation.

    PubMed

    Mo, Chenglin; Romero-Suarez, Sandra; Bonewald, Lynda; Johnson, Mark; Brotto, Marco

    2012-12-01

    Prostaglandin E(2) (PGE(2)), a prostanoid synthesized from arachidonic acid via the cyclooxygenase pathway, is a modulator of physiological responses including inflammation, fever, and muscle regeneration. Several patents have been filed that are related to PGE(2), one of them being directly related to skeletal muscles. In this report, we first summarize the key patents describing inventions for the utilization of PGE(2) for either diagnostic or therapeutic purposes, including skeletal muscle. In the second part of our work we present new and exciting data that demonstrates that PGE(2) accelerates skeletal muscle myogenic differentiation. Our discovery resulted from our recent and novel concept of bone-muscle crosstalk. Bone and muscle are anatomically intimate endocrine organs and we aimed to determine whether this anatomical intimacy also translates into a biochemical communication from bone cells to muscle cells at the in vitro level. The effects of MLOY4 osteocyte-like cell conditioned medium (CM) and three osteocyte-secreted factors, PGE(2), sclerostin and monocyte chemotactic protein (MCP-3), on C2C12 myogenic differentiation were evaluated using morphological analyses, a customized 96-gene PCR array, and measurements of intracellular calcium levels. MLO-Y4 CM and PGE(2), but not sclerostin and MCP-3, induced acceleration of myogenesis of C2C12 myoblasts that was linked with significant modifications in intracellular calcium homeostasis. This finding should further stimulate the pursuit of new patents to explore the use of PGE(2) and the new concept of bone-muscle crosstalk for the development and application of inventions designed to treat muscle diseases characterized by enhanced muscle wasting, such as sarcopenia.

  14. Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.

    PubMed

    Intini, G; Katsuragi, Y; Kirkwood, K L; Yang, S

    2014-05-01

    This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of

  15. The osteogenic potential of human bone callus

    PubMed Central

    Han, Weiqi; He, Wei; Yang, Wanlei; Li, Jianlei; Yang, Zhifan; Lu, Xuanyuan; Qin, An; Qian, Yu

    2016-01-01

    Bone callus, generated during fracture healing, is commonly discarded during surgical procedures. The aim of this study was to investigate the osteogenic potential of bone callus and its possible use as autograft material for patients needing bone grafts. Histology, immunohistochemistry, micro-computed tomography, and biomechanics were performed to examine osteogenic cells, osteoinductive factors, and the osteoconductive structure of bone callus. Alkaline phosphatase-positive osteoblasts, osteoinductive factors (including BMP2, FGF2, TGFB1, and IGF1), and a porous structure were found in bone callus. Early-stage callus (within 3 months after fracture) presented significantly improved osteogenic properties compared to medium- (3–9 months) and late-stage (longer than 9 months) callus. The results revealed that bone callus induced new bone formation in a nude mouse model. Early-stage callus showed better performance to medium- and late-stage callus in the induction of new bone formation at both 8 and 12 weeks. These findings indicated that bone callus, especially early-stage callus, possesses osteogenic potential and can potentially serve as an alternative source of material for bone grafts. PMID:27796345

  16. Human progenitor cells for bone engineering applications.

    PubMed

    de Peppo, G M; Thomsen, P; Karlsson, C; Strehl, R; Lindahl, A; Hyllner, J

    2013-06-01

    In this report, the authors review the human skeleton and the increasing burden of bone deficiencies, the limitations encountered with the current treatments and the opportunities provided by the emerging field of cell-based bone engineering. Special emphasis is placed on different sources of human progenitor cells, as well as their pros and cons in relation to their utilization for the large-scale construction of functional bone-engineered substitutes for clinical applications. It is concluded that, human pluripotent stem cells represent a valuable source for the derivation of progenitor cells, which combine the advantages of both embryonic and adult stem cells, and indeed display high potential for the construction of functional substitutes for bone replacement therapies.

  17. Bone densitometry: applications and limitations.

    PubMed

    Syed, Zeba; Khan, Aliya

    2002-06-01

    Osteoporosis is clinically diagnosed in its advanced stages, usually following a fracture. Accurate, precise, and noninvasive skeletal assessment is now possible for early detection of osteoporosis at a preclinical stage. Currently, the gold standard in bone mass measurement and fracture prediction is dual energy X-ray absorptiometry (DEXA) of the hip and spine. Exponential increases in fracture risk have been observed with small decreases in bone mineral density. Bone mineral density (BMD) should be considered in conjunction with independent clinical risk factors for fracture, including: low body weight, history of postmenopausal fracture, family history of fracture, and poor neuromuscular function. The World Health Organization (WHO) diagnostic criteria for osteoporosis and osteopenia are appropriate for postmenopausal Caucasian women and are applicable to DEXA assessments at the hip, spine, or forearm. This review explores the relationship between BMD and fracture risk, the principles of bone densitometry interpretation, and the applications as well as the limitations of DEXA technology, and presents cases illustrating common errors seen in the interpretation of DEXA studies.

  18. Physicochemical, antioxidant and biocompatible properties of chondroitin sulphate isolated from chicken keel bone for potential biomedical applications.

    PubMed

    Rani, Aruna; Baruah, Rwivoo; Goyal, Arun

    2017-03-01

    Chicken keel bone cartilage was explored for cheaper and sustainable source for isolation of chondroitin sulphate (CS) for its future use in tissue engineering and pharmaceutical industry. HPSEC analysis displayed two peaks of 100kDa for CS-keel polysaccharide and 1kDa for protein. DLS analysis of CS-keel displayed polydispersity. CS-keel yield was 15% and 53±5% uronic acid content. The quantified percentages of UA-GalNAc4S and UA-GalNAc6S disaccharide in CS-keel were 58% and 42%, respectively. FT-IR identified CS-keel to be chondroitin 4-sulphate. (1)H NMR of CS-keel confirmed the presence of N-acetylgalactosamine and Glucuronic acid. FESEM demonstrated layer structure and AFM displayed the size of CS-keel fibres. DSC, TGA and DTG studies of CS-keel showed Td at 243°C. In vitro cell proliferation assay and morphological analysis of mouse fibroblast L929 cell lines confirmed the biocompatibility of CS-keel. CS-keel (5mg/ml) exhibited ∼49% antioxidant activity against DPPH and 22% against superoxide radical protecting from oxidative damage. CS-keel demonstrated better (70.3%) emulsifying activity than commercial sodium alginate (60.2%).

  19. Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

    PubMed

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

    2017-03-30

    A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures.

  20. Laser Application on Orthopaedic Bone Repair

    DTIC Science & Technology

    2011-09-01

    Body weight gain in the laser-treated animals was similar to that in non -laser treated animals during the healing period. These results showed a...technology to replace bone loss. However, major complications reported for grafting procedures are infection, bone graft fracture, non -union at the graft...Recent reports indicates Er:YAG laser provides; (1) advantageous bone surface for bone tissue repair; (2) bactericidal effect; (3) applications for

  1. Potential Operating Room Fire Hazard of Bone Cement.

    PubMed

    Sibia, Udai S; Connors, Kevin; Dyckman, Sarah; Zahiri, Hamid R; George, Ivan; Park, Adrian E; MacDonald, James H

    Approximately 600 cases of operating room (OR) fires are reported annually. Despite extensive fire safety education and training, complete elimination of OR fires still has not been achieved. Each fire requires an ignition source, a fuel source, and an oxidizer. In this case report, we describe the potential fire hazard of bone cement in the OR. A total knee arthroplasty was performed with a standard medial parapatellar arthrotomy. Tourniquet control was used. After bone cement was applied to the prepared tibial surface, the surgeon used an electrocautery device to resect residual lateral meniscus tissue-and started a fire in the operative field. The surgeon suffocated the fire with a dry towel and prevented injury to the patient. We performed a PubMed search with a cross-reference search for relevant papers and found no case reports outlining bone cement as a potential fire hazard in the OR. To our knowledge, this is the first case report identifying bone cement as a fire hazard. OR fires related to bone cement can be eliminated by correctly assessing the setting time of the cement and avoiding application sites during electrocautery.

  2. Investigation of potential injectable polymeric biomaterials for bone regeneration

    PubMed Central

    Dreifke, Michael B.; Ebraheim, Nabil A.; Jayasuriya, Ambalangodage C.

    2014-01-01

    This article reviews the potential injectable polymeric biomaterial scaffolds currently being investigated for application in bone tissue regeneration. Two types of injectable biomaterial scaffolds are focused in this review, including injectable microspheres and injectable gels. The injectable microspheres section covers several polymeric materials, including poly(l-lactide-co-glycolide)-PLGA, poly (propylene fumarate), and chitosan. The injectable gel section covers alginate gels, hyaluronan hydrogels, poly(ethylene-glycol)-PEG hydrogels, and PEG-PLGA copolymer hydrogels. This review focuses on the effect of cellular behaviorin vitro andin vivo in terms of material properties of polymers, such as biodegradation, biocompatibility, porosity, microsphere size, and cross-linking nature. Injectable polymeric biomaterials offer a major advantage for orthopedic applications by allowing the ability to use noninvasive or minimally invasive treatment methods. Therefore, combining injectable polymeric biomaterial scaffolds with cells have a significant potential to treat orthopedic bone defects, including spine fusion, and craniofacial and periodontal defects. PMID:23401336

  3. Investigation of potential injectable polymeric biomaterials for bone regeneration.

    PubMed

    Dreifke, Michael B; Ebraheim, Nabil A; Jayasuriya, Ambalangodage C

    2013-08-01

    This article reviews the potential injectable polymeric biomaterial scaffolds currently being investigated for application in bone tissue regeneration. Two types of injectable biomaterial scaffolds are focused in this review, including injectable microspheres and injectable gels. The injectable microspheres section covers several polymeric materials, including poly(L-lactide-co-glycolide)-PLGA, poly(propylene fumarate), and chitosan. The injectable gel section covers alginate gels, hyaluronan hydrogels, poly(ethylene-glycol)-PEG hydrogels, and PEG-PLGA copolymer hydrogels. This review focuses on the effect of cellular behavior in vitro and in vivo in terms of material properties of polymers, such as biodegradation, biocompatibility, porosity, microsphere size, and cross-linking nature. Injectable polymeric biomaterials offer a major advantage for orthopedic applications by allowing the ability to use noninvasive or minimally invasive treatment methods. Therefore, combining injectable polymeric biomaterial scaffolds with cells have a significant potential to treat orthopedic bone defects, including spine fusion, and craniofacial and periodontal defects.

  4. Preparation and characterization of polylactide/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) hybrid fibers for potential application in bone tissue engineering

    PubMed Central

    Wang, YueLong; Guo, Gang; Chen, HaiFeng; Gao, Xiang; Fan, RangRang; Zhang, DongMei; Zhou, LiangXue

    2014-01-01

    The aim of this study was to develop a kind of osteogenic biodegradable composite graft consisting of human placenta-derived mesenchymal stem cell (hPMSC) material for site-specific repair of bone defects and attenuation of clinical symptoms. The novel nano- to micro-structured biodegradable hybrid fibers were prepared by electrospinning. The characteristics of the hybrid membranes were investigated by a range of methods, including Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Morphological study with scanning electron microscopy showed that the average fiber diameter and the number of nanoscale pores on each individual fiber surface decreased with increasing concentration of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC). The prepared polylactide (PLA)/PCEC fibrous membranes favored hPMSC attachment and proliferation by providing an interconnected, porous, three-dimensional mimicked extracellular environment. What is more, hPMSCs cultured on the electrospun hybrid PLA/PCEC fibrous scaffolds could be effectively differentiated into bone-associated cells by positive alizarin red staining. Given the good cellular response and excellent osteogenic potential in vitro, the electrospun PLA/PCEC fibrous scaffolds could be one of the most promising candidates for bone tissue engineering. PMID:24790439

  5. Preparation and characterization of polylactide/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) hybrid fibers for potential application in bone tissue engineering.

    PubMed

    Wang, YueLong; Guo, Gang; Chen, HaiFeng; Gao, Xiang; Fan, RangRang; Zhang, DongMei; Zhou, LiangXue

    2014-01-01

    The aim of this study was to develop a kind of osteogenic biodegradable composite graft consisting of human placenta-derived mesenchymal stem cell (hPMSC) material for site-specific repair of bone defects and attenuation of clinical symptoms. The novel nano- to micro-structured biodegradable hybrid fibers were prepared by electrospinning. The characteristics of the hybrid membranes were investigated by a range of methods, including Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Morphological study with scanning electron microscopy showed that the average fiber diameter and the number of nanoscale pores on each individual fiber surface decreased with increasing concentration of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC). The prepared polylactide (PLA)/PCEC fibrous membranes favored hPMSC attachment and proliferation by providing an interconnected, porous, three-dimensional mimicked extracellular environment. What is more, hPMSCs cultured on the electrospun hybrid PLA/PCEC fibrous scaffolds could be effectively differentiated into bone-associated cells by positive alizarin red staining. Given the good cellular response and excellent osteogenic potential in vitro, the electrospun PLA/PCEC fibrous scaffolds could be one of the most promising candidates for bone tissue engineering.

  6. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    SciTech Connect

    Campbell, Belinda A.; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S.; Hicks, Rodney J.; Burbury, Kate; MacManus, Michael

    2015-08-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

  7. Biomimetically enhanced demineralized bone matrix for bone regenerative applications

    PubMed Central

    Ravindran, Sriram; Huang, Chun-Chieh; Gajendrareddy, Praveen; Narayanan, Raghuvaran

    2015-01-01

    Demineralized bone matrix (DBM) is one of the most widely used bone graft materials in dentistry. However, the ability of DBM to reliably and predictably induce bone regeneration has always been a cause for concern. The quality of DBM varies greatly depending on several donor dependent factors and also manufacturing techniques. In order to standardize the quality and to enable reliable and predictable bone regeneration, we have generated a biomimetically-enhanced version of DBM (BE-DBM) using clinical grade commercial DBM as a control. We have generated the BE-DBM by incorporating a cell-derived pro-osteogenic extracellular matrix (ECM) within clinical grade DBM. In the present study, we have characterized the BE-DBM and evaluated its ability to induce osteogenic differentiation of human marrow derived stromal cells (HMSCs) with respect to clinical grade commercial DBM. Our results indicate that the BE-DBM contains significantly more pro-osteogenic factors than DBM and enhances HMSC differentiation and mineralized matrix formation in vitro and in vivo. Based on our results, we envision that the BE-DBM has the potential to replace DBM as the bone graft material of choice. PMID:26557093

  8. Potential Applications for AQUATOX

    EPA Pesticide Factsheets

    AQUATOX has a myriad of potential applications to water management issues and programs, including water quality criteria and standards, TMDLs (Total Maximum Daily Loads), and ecological risk assessments of aquatic systems.

  9. 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

  10. Application of Petri nets in bone remodeling.

    PubMed

    Li, Lingxi; Yokota, Hiroki

    2009-07-06

    Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs) have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs), which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  11. Angiogenic and Osteogenic Potential of Bone Repair Cells for Craniofacial Regeneration

    PubMed Central

    Pagni, Giorgio; Park, Chan-Ho; Tarle, Susan A.; Bartel, Ronnda L.; Giannobile, William V.

    2010-01-01

    There has been increased interest in the therapeutic potential of bone marrow derived cells for tissue engineering applications. Bone repair cells (BRCs) represent a unique cell population generated via an ex vivo, closed-system, automated cell expansion process, to drive the propagation of highly osteogenic and angiogenic cells for bone engineering applications. The aims of this study were (1) to evaluate the in vitro osteogenic and angiogenic potential of BRCs, and (2) to evaluate the bone and vascular regenerative potential of BRCs in a craniofacial clinical application. BRCs were produced from bone marrow aspirates and their phenotypes and multipotent potential characterized. Flow cytometry demonstrated that BRCs were enriched for mesenchymal and vascular phenotypes. Alkaline phosphatase and von Kossa staining were performed to assess osteogenic differentiation, and reverse transcriptase–polymerase chain reaction was used to determine the expression levels of bone specific factors. Angiogenic differentiation was determined through in vitro formation of tube-like structures and fluorescent labeling of endothelial cells. Finally, 6 weeks after BRC transplantation into a human jawbone defect, a biopsy of the regenerated site revealed highly vascularized, mineralized bone tissue formation. Taken together, these data provide evidence for the multilineage and clinical potential of BRCs for craniofacial regeneration. PMID:20412009

  12. Degradation pattern of porous CaCO3 and hydroxyapatite microspheres in vitro and in vivo for potential application in bone tissue engineering.

    PubMed

    Zhong, Qiwei; Li, Wenhua; Su, Xiuping; Li, Geng; Zhou, Ying; Kundu, Subhas C; Yao, Juming; Cai, Yurong

    2016-07-01

    Despite superior clinical handling, excellent biocompatibility, biodegradation property of calcium phosphate needs to be improved to coincide with the rate of new bone formation. In this study, spherical CaCO3 are fabricated in the presence of the silk sericin and then transformed into porous hydroxyapatite (HAP) microspheres via hydrothermal method. The degradation behavior of obtained CaCO3, HAP and their mixture is first investigated in vitro. The result demonstrates that the weight loss of HAP microspheres are almost 24.3% after immersing in pH 7.40 Tris-HCl buffer solution for 12 weeks, which is far slower than that of spherical CaCO3 (97.5%). The degradation speed of the mixtures depends on the proportion of CaCO3 and HAP. The mixture with higher content of CaCO3 possesses a quicker degradation speed. The obtained CaCO3 and HAP microspheres are injected into subcutaneous tissue of ICR mice with the assistance of sodium alginate. The result in vivo also shows an obvious difference of degradation speed between the obtained CaCO3 and HAP microspheres, implying it is feasible to modulate the degradation property of the mixture through changing the proportion of CaCO3 and HAP The good cytocompatibility of the two kinds of microspheres is proved and a mild inflammation response is observed only at early stage of implantation. The job offers a simple method to modify the degradation properties of biomaterial for potential use in bone tissue engineering.

  13. Vitamin D and bone health: potential mechanisms.

    PubMed

    Laird, Eamon; Ward, Mary; McSorley, Emeir; Strain, J J; Wallace, Julie

    2010-07-01

    Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets) and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms.

  14. Dynamic skeletal muscle stimulation and its potential in bone adaptation

    PubMed Central

    Qin, Y-X.; Lam, H.; Ferreri, S.; Rubin, C.

    2016-01-01

    To identify mechanotransductive signals for combating musculoskeletal deterioration, it is essential to determine the components and mechanisms critical to the anabolic processes of musculoskeletal tissues. It is hypothesized that the interaction between bone and muscle may depend on fluid exchange in these tissues by mechanical loading. It has been shown that intramedullary pressure (ImP) and low-level bone strain induced by muscle stimulation (MS) has the potential to mitigate bone loss induced by disuse osteopenia. Optimized MS signals, i.e., low-intensity and high frequency, may be critical in maintaining bone mass and mitigating muscle atrophy. The objectives for this review are to discuss the potential for MS to induce ImP and strains on bone, to regulate bone adaptation, and to identify optimized stimulation frequency in the loading regimen. The potential for MS to regulate blood and fluid flow will also be discussed. The results suggest that oscillatory MS regulates fluid dynamics with minimal mechanical strain in bone. The response was shown to be dependent on loading frequency, serving as a critical mediator in mitigating bone loss. A specific regimen of dynamic MS may be optimized in vivo to attenuate disuse osteopenia and serve as a biomechanical intervention in the clinical setting. PMID:20190376

  15. Terrestrial applications of bone and muscle research in microgravity.

    PubMed

    Booth, F W

    1994-01-01

    Major applications to people on Earth are possible from NASA-sponsored research on bone and muscle which is conducted either in microgravity or on Earth using models mimicking microgravity. In microgravity bone and muscle mass are lost. Humans experience a similar loss under certain conditions on Earth. Bone and muscle loss exist on Earth as humans age from adulthood to senescence, during limb immobilization for healing of orthopedic injuries, during wheelchair confinement because of certain diseases, and during chronic bed rest prescribed for curing of diseases. NASA-sponsored research is dedicated to learning both what cause bone and muscle loss as well as finding out how to prevent this loss. The health ramifications of these discoveries will have major impact. Objective 1.6 of Healthy People 2000, a report from the U.S. Department of Health and Human Services, states that the performance of physical activities that improve muscular strength, muscular endurance, and flexibility is particularly important to maintaining functional independence and social integration in older adults. This objective further states that these types of physical activities are important because they may protect against disability, an event which costs the U.S. economy huge sums of money. Thus NASA research related to bone and muscle loss has potential major impact on the quality of life in the U.S. Relative to its potential health benefits, NASA and Congressional support of bone and muscle research is funded at a very low level.

  16. Terrestrial applications of bone and muscle research in microgravity

    NASA Astrophysics Data System (ADS)

    Booth, F. W.

    1994-08-01

    Major applications to people on Earth are possible from NASA-sponsored research on bone and muscle which is conducted either in microgravity or on Earth using models mimicking microgravity. In microgravity bone and muscle mass are lost. Humans experience a similar loss under certain conditions on Earth. Bone and muscle loss exist on Earth as humans age from adulthood to senescence, during limb immobilization for healing of orthopedic injuries, during wheelchair confinement because of certain diseases, and during chronic bed rest prescribed for curing of diseases. NASA-sponsored research is dedicated to learning both what cause bone and muscle loss as well as finding out how to prevent this loss. The health ramifications of these discoveries will have major impact. Objective 1.6 of Healthy People 2000, a report from the U.S. Department of Health and Human Services, states that the performance of physical activities that improve muscular strength, muscular endurance, and flexibility is particularly important to maintaining functional independence and social integration in older adults /1/. This objective further states that these types of physical activities are important because they may protect against disability, an event which costs the U.S. economy hugh sums of money. Thus NASA research related to bone and muscle loss has potential major impact on the quality of life in the U.S. Relative to its potential health benefits, NASA and Congressional support of bone and muscle research is funded is a very low level.

  17. Laser Applications on Orthopaedic Bone Repair

    DTIC Science & Technology

    2012-03-01

    Award Number: W81XWH-10-1-0627 TITLE:“Laser Applications on Orthopaedic Bone Repair” PRINCIPAL INVESTIGATOR: Kotaro Sena , D.D.S., Ph.D...6. AUTHOR(S) 5d. PROJECT NUMBER Kotaro Sena , D.D.S., Ph.D.; Amarjit S. Virdi, Ph.D. 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION

  18. Modeling fluorescence recovery after photobleaching in loaded bone: potential applications in measuring fluid and solute transport in the osteocytic lacunar-canalicular system.

    PubMed

    Zhou, Xiaozhou; Novotny, John E; Wang, Liyun

    2008-12-01

    Solute transport through the bone lacunar-canalicular system is essential for osteocyte viability and function, and it can be measured using fluorescence recovery after photobleaching (FRAP). The mathematical model developed here aims to analyze solute transport during FRAP in mechanically loaded bone. Combining both whole bone-level poroelasticity and cellular-level solute transport, we found that load-induced solute transport during FRAP is characterized by an exponential recovery rate, which is determined by the dimensionless Strouhal (St) number that characterizes the oscillation effects over the mean flows, and that significant transport occurs only for St values below a threshold, when the solute stroke displacement exceeds the distance between the source and sink (the canalicular length). This threshold mechanism explains the general flow behaviors such as increasing transport with increasing magnitude and decreasing frequency. Mechanical loading is predicted to enhance transport of all tracers relative to diffusion, with the greatest enhancement for medium-sized tracers and less enhancement for small and large tracers. This study provides guidelines for future FRAP experiments, based on which the model can be used to quantify bone permeability, solute-matrix interaction, and flow velocities. These studies should provide insights into bone adaptation and metabolism, and help to treat various bone diseases and conditions.

  19. Phosphorylated, cellulose-based substrates as potential adsorbents for bone morphogenetic proteins in biomedical applications: a protein adsorption screening study using cytochrome C as a bone morphogenetic protein mimic.

    PubMed

    Mucalo, Michael R; Kato, Katsuya; Yokogawa, Yoshiyuki

    2009-06-01

    Screening studies aimed at identifying useful biomedical materials that (when combined with implants) can attract bone morphogenetic proteins to their surfaces have been conducted. In this paper, the screening process has involved carrying out protein adsorption studies using cytochrome C, as a BMP protein mimic on phosphorylated cellulose-based substrates. These studies have shown that phosphorylation of cellulose produces materials that are capable of attracting the adsorption of cytochrome C to their surface. In contrast, negligible cytochrome C adsorption was observed on the unphosphorylated cellulose-based materials. The selective uptake of the positively charged cytochrome C (from solutions at pH 9.51) by the negatively charged phosphorylated cotton and microcrystalline cellulose substrates was primarily due to this protein's high isoelectric point (i.e.p) of 9.8 which gives it a positive charge at pHpotential use for selective BMP adsorption onto biomedical materials, have not been reported directly in the literature. The work thus shows that the phosphorylated cellulose-based substrates should be seriously considered as carrier materials that could be used (with preloaded BMPs) as part of an implant system to assist in implant healing.

  20. Singled-walled carbon nanotubes produced by induction thermal plasma: Cytotoxicity evaluation of the feedstock materials and the final product for a potential bone application

    NASA Astrophysics Data System (ADS)

    Alinejad, Yasaman

    One of the most challenging issues that the technologies related to nanomaterials face is the impact they have on human health and environment. It is therefore of great importance to investigate the toxicological impacts of these technologies prior to their widespread utilization in different fields of application. Therefore, in this study, the cytotoxicity of the materials present throughout the process of single-walled carbon nanotubes (SWCNTs) synthesis by induction thermal plasma (from the feedstock materials to the final product) was evaluated. First of all, the influence of the induction thermal plasma process on the physico-chemical and cytotoxic properties of feedstock materials (i.e. commercial Co, Ni, Y2O3, Mo catalysts and carbon black) was investigated. The strongest cytotoxicity was observed for commercial Co compared to other catalysts. Although the thermal plasma process affected the properties of all catalysts, only the cytotoxicity of Ni was increased. Comparing the properties and cytotoxicity of the plasma treated Ni particles with commercial Ni nanoparticles revealed that the particles with similar surface area had different cytotoxicities. Plus, the observed cytotoxicity of the catalysts was not mainly due to the release of ions. In order to evaluate the capacity of the RF induction thermal plasma process to produce high quality SWCNTs using non-toxic catalysts, the effects of the type and quantity of three catalyst mixtures (Ni-Y2O 3, Ni-Co-Y2O3, and Ni-Mo-Y2O3 ) on SWCNTs synthesis were examined. Thermodynamic calculations, in gas and particularly in liquid solution phases, were also performed. The results showed that catalyst type affected the quality of the SWCNT final product and similar quality SWCNTs was produced when the same amount of Co was replaced by Ni. Then, to investigate the cytotoxicity of the SWCNTs produced with the three catalyst mixtures, their effect was evaluated on the behavior of murine MC3T3-E1 preosteoblasts. Either

  1. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.

    PubMed

    Higashino, Kosaku; Viggeswarapu, Manjula; Bargouti, Maggie; Liu, Hui; Titus, Louisa; Boden, Scott D

    2011-02-01

    The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

  2. 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

  3. [Bone morphogenetic proteins (BMP): clinical application for reconstruction of bone defects].

    PubMed

    Sierra-García, Gerardo Daniel; Castro-Ríos, Rocío; Gónzalez-Horta, Azucena; Lara-Arias, Jorge; Chávez-Montes, Abelardo

    2016-01-01

    Since the introduction of bone morphogenetic proteins, their use has become an invaluable ally for the treatment of bone defects. These proteins are potent growth factors, related to angiogenic and osteogenic activity. The osteoinductive capacity of recombinant bone morphogenetic protein (rhBMP) in the formation of bone and cartilage has been confirmed in in vitro studies and evaluated in clinical trials. To obtain a therapeutic effect, administration is systemic, by injection over the physiological dose. Among the disadvantages, ectopic bone formation or high morbidity in cases of spinal fusion is observed. In this review, the roles of bone morphogenetic proteins in bone repair and clinical applications are analyzed. These findings represent advances in the study of bone regeneration and application of growth factors for more predictable results.

  4. Strontium borate glass: potential biomaterial for bone regeneration.

    PubMed

    Pan, H B; Zhao, X L; Zhang, X; Zhang, K B; Li, L C; Li, Z Y; Lam, W M; Lu, W W; Wang, D P; Huang, W H; Lin, K L; Chang, J

    2010-07-06

    Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones.

  5. Application potential of bone marrow mesenchymal stem cell (BMSCs) based tissue-engineering for spinal cord defect repair in rat fetuses with spina bifida aperta.

    PubMed

    Li, Xiaoshuai; Yuan, Zhengwei; Wei, Xiaowei; Li, Hui; Zhao, Guifeng; Miao, Jiaoning; Wu, Di; Liu, Bo; Cao, Songying; An, Dong; Ma, Wei; Zhang, Henan; Wang, Weilin; Wang, Qiushi; Gu, Hui

    2016-04-01

    Spina bifida aperta are complex congenital malformations resulting from failure of fusion in the spinal neural tube during embryogenesis. Despite surgical repair of the defect, most patients who survive with spina bifida aperta have a multiple system handicap due to neuron deficiency of the defective spinal cord. Tissue engineering has emerged as a novel treatment for replacement of lost tissue. This study evaluated the prenatal surgical approach of transplanting a chitosan-gelatin scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in the healing the defective spinal cord of rat fetuses with retinoic acid induced spina bifida aperta. Scaffold characterisation revealed the porous structure, organic and amorphous content. This biomaterial promoted the adhesion, spreading and in vitro viability of the BMSCs. After transplantation of the scaffold combined with BMSCs, the defective region of spinal cord in rat fetuses with spina bifida aperta at E20 decreased obviously under stereomicroscopy, and the skin defect almost closed in many fetuses. The transplanted BMSCs in chitosan-gelatin scaffold survived, grew and expressed markers of neural stem cells and neurons in the defective spinal cord. In addition, the biomaterial presented high biocompatibility and slow biodegradation in vivo. In conclusion, prenatal transplantation of the scaffold combined with BMSCs could treat spinal cord defect in fetuses with spina bifida aperta by the regeneration of neurons and repairmen of defective region.

  6. Joint loading modality: its application to bone formation and fracture healing.

    PubMed

    Zhang, P; Malacinski, G M; Yokota, H

    2008-07-01

    Sports-related injuries such as impact and stress fractures often require a rehabilitation programme to stimulate bone formation and accelerate fracture healing. This review introduces a recently developed joint loading modality and evaluates its potential applications to bone formation and fracture healing in post-injury rehabilitation. Bone is a dynamic tissue whose structure is constantly altered in response to its mechanical environments. Indeed, many loading modalities can influence the bone remodelling process. The joint loading modality is, however, able to enhance anabolic responses and accelerate wound healing without inducing significant in situ strain at the site of bone formation or fracture healing. This review highlights the unique features of this loading modality and discusses its potential underlying mechanisms as well as possible clinical applications.

  7. Colony-stimulating factor 1 potentiates lung cancer bone metastasis.

    PubMed

    Hung, Jaclyn Y; Horn, Diane; Woodruff, Kathleen; Prihoda, Thomas; LeSaux, Claude; Peters, Jay; Tio, Fermin; Abboud-Werner, Sherry L

    2014-04-01

    Colony-stimulating factor 1 (CSF1) is essential for osteoclastogenesis that mediates osteolysis in metastatic tumors. Patients with lung cancer have increased CSF1 in serum and high levels are associated with poor survival. Adenocarcinomas metastasize rapidly and many patients suffer from bone metastasis. Lung cancer stem-like cells sustain tumor growth and potentiate metastasis. The purpose of this study was to determine the role of CSF1 in lung cancer bone metastasis and whether inhibition of CSF1 ameliorates the disease. Human lung adenocarcinoma A549 cells were examined in vitro for CSF1/CSF1R. A549-luc cells were injected intracardiac in NOD/SCID mice and metastasis was assessed. To determine the effect of CSF1 knockdown (KD) in A549 cells on bone metastasis, cells were stably transfected with a retroviral vector containing short-hairpin CSF1 (KD) or empty vector (CT). Results showed that A549 cells express CSF1/CSF1R; CSF1 increased their proliferation and invasion, whereas soluble CSF1R inhibited invasion. Mice injected with A549-luc cells showed osteolytic bone lesions 3.5 weeks after injection and lesions increased over 5 weeks. Tumors recapitulated adenocarcinoma morphology and showed osteoclasts along the tumor/bone interface, trabecular, and cortical bone loss. Analyses of KD cells showed decreased CSF1 protein levels, reduced colony formation in soft agar assay, and decreased fraction of stem-like cells. In CSF1KD mice, the incidence of tumor metastasis was similar to controls, although fewer CSF1KD mice had metastasis in both hind limbs. KD tumors showed reduced CSF1 expression, Ki-67+ cells, and osteoclasts. Importantly, there was a low incidence of large tumors >0.1 mm(2) in CSF1KD mice compared with control mice (10% vs 62.5%). This study established a lung osteolytic bone metastasis model that resembles human disease and suggests that CSF1 is a key determinant of cancer stem cell survival and tumor growth. Results may lead to novel strategies to

  8. Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

    NASA Astrophysics Data System (ADS)

    Tsuneda, H.; Matsukawa, S.; Takayanagi, S.; Mizuno, K.; Yanagitani, T.; Matsukawa, M.

    2015-02-01

    The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurements and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

  9. Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

    SciTech Connect

    Tsuneda, H.; Matsukawa, S.; Takayanagi, S.; Matsukawa, M.; Mizuno, K.; Yanagitani, T.

    2015-02-16

    The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurements and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

  10. An Update into the Application of Nanotechnology in Bone Healing

    PubMed Central

    Brannigan, K.; Griffin, M.

    2016-01-01

    Background Bone differs from other organs in that it can regenerate and remodel without scar formation. There are instances of trauma, congenital bone disorder, bone disease and bone cancer where this is not possible. Without bone grafts and implants, deformity and disability would result. Human bone grafts are limited in their management of large or non-union fractures. In response, synthetic bone grafts and implants are available to the Orthopaedic Surgeon. Unfortunately these also have their limitations and associated complications. Nanotechnology involves the research, design and manufacture of materials with a grain size less than 100nm. Nano-phase materials follow the laws of quantum physics, not classical mechanics, resulting in novel behavioural differences compared to conventional counterparts. Methods: Past, present and future nanotechnology in bone healing literature is reviewed and discussed. The article highlights concepts which are likely to be instrumental to the future of nanotechnology in bone healing. Results: Nanotechnology in bone healing is an emerging field within Orthopaedic Surgery. There is a requirement for bone healing technologies which are biochemically and structurally similar to bone. Nanotechnology is a potential solution as the arrangement of bone includes nanoscopic collagen fibres and hydroxyapatite. This review centers on the novel field of nanotechnology in bone healing with discussion focusing on advances in bone grafts, implants, diagnostics and drug delivery. Conclusion: The concept of nanotechnology was first introduced in 1959. Current nanoproducts for bone healing include nano-HA-paste-ostim and nano-beta-tricalcium phosphate-Vitoss. Nanophase technologies are considered to be superior bone healing solutions. Limited safety data and issues regarding cost and mass scale production require further research into this exciting field. PMID:28217207

  11. Potential biomedical applications of ion beam technology

    NASA Technical Reports Server (NTRS)

    Banks, B. A.; Weigand, A. J.; Babbush, C. A.; Vankampen, C. L.

    1976-01-01

    Electron bombardment ion thrusters used as ion sources have demonstrated a unique capability to vary the surface morphology of surgical implant materials. The microscopically rough surface texture produced by ion beam sputtering of these materials may result in improvements in the biological response and/or performance of implanted devices. Control of surface roughness may result in improved attachment of the implant to soft tissue, hard tissue, bone cement, or components deposited from blood. Potential biomedical applications of ion beam texturing discussed include: vascular prostheses, artificial heart pump diaphragms, pacemaker fixation, percutaneous connectors, orthopedic pros-thesis fixtion, and dental implants.

  12. Potential biomedical applications of ion beam technology

    NASA Technical Reports Server (NTRS)

    Banks, B. A.; Weigand, A. J.; Van Kampen, C. L.; Babbush, C. A.

    1976-01-01

    Electron bombardment ion thrusters used as ion sources have demonstrated a unique capability to vary the surface morphology of surgical implant materials. The microscopically rough surface texture produced by ion beam sputtering of these materials may result in improvements in the biological response and/or performance of implanted devices. Control of surface roughness may result in improved attachment of the implant to soft tissue, hard tissue, bone cement, or components deposited from blood. Potential biomedical applications of ion beam texturing discussed include: vascular prostheses, artificial heart pump diaphragms, pacemaker fixation, percutaneous connectors, orthopedic prosthesis fixation, and dental implants.

  13. Digital image processing of bone - Problems and potentials

    NASA Technical Reports Server (NTRS)

    Morey, E. R.; Wronski, T. J.

    1980-01-01

    The development of a digital image processing system for bone histomorphometry and fluorescent marker monitoring is discussed. The system in question is capable of making measurements of UV or light microscope features on a video screen with either video or computer-generated images, and comprises a microscope, low-light-level video camera, video digitizer and display terminal, color monitor, and PDP 11/34 computer. Capabilities demonstrated in the analysis of an undecalcified rat tibia include the measurement of perimeter and total bone area, and the generation of microscope images, false color images, digitized images and contoured images for further analysis. Software development will be based on an existing software library, specifically the mini-VICAR system developed at JPL. It is noted that the potentials of the system in terms of speed and reliability far exceed any problems associated with hardware and software development.

  14. Operculum bone carp (cyprinus carprio sp.) scaffold is a new potential xenograft material: a preliminary study

    NASA Astrophysics Data System (ADS)

    Kartiwa, A.; Abbas, B.; Pandansari, P.; Prahasta, A.; Nandini, M.; Fadhlillah, M.; Subroto, T.; Panigoro, R.

    2017-02-01

    Orbital floor fracture with extensive bone loss, would cause herniation of the orbital tissue into the maxillary sinus. Graft implantation should be done on the orbital fracture with extensive bone loss. Different types of grafts have their own characteristics and advantages. Xenograft has been widely studied for use in bone defects. This study was to investigate cyprinus carprio sp. opercula bone as a potential xenograft. The aim of this study was to investigate based on EDS chemical analysis using a ZAF Standardless Method of Quantitative Analysis (Oxide) and SEM examination conducted in the laboratory of Mathematics, Institute of Technology Bandung. Particularly the mass ratio of Ca and P (5.8/3:47), the result is 1.67. This is equivalent to the stoichiometric Hydroxyapatite (HA) (Aoki H, 1991, Science and medical applications of hydroxyapatite, Tokyo: Institute for Medical and Engineering, Tokyo Medical and Dental University). C N O that there is an element of protein/amino acid collagen compound, serves as a matrix together with HA. As shown in the SEM analysis that the matrix is a porous sheet-shaped (oval) that interconnect with each other, which is good scaffold. The pore is composed of large pores >200 microns and smaller pores between the large pores with a size smaller or equal to 10 microns that can serve for the attachment of osteoblast cell. In conclusion, Opercula bone carp (cyprinus carprio sp.) scaffold could be a new potential xenograft material.

  15. Guided Bone Regeneration: biological principle and therapeutic applications.

    PubMed

    Retzepi, Maria; Donos, N

    2010-06-01

    The Guided Bone Regeneration (GBR) treatment concept advocates that regeneration of osseous defects is predictably attainable via the application of occlusive membranes, which mechanically exclude non-osteogenic cell populations from the surrounding soft tissues, thereby allowing osteogenic cell populations originating from the parent bone to inhabit the osseous wound. The present review discusses the evolution of the GBR biological rationale and therapeutic concept over the last two decades. Further, an overview of the GBR research history is provided with specific focus on the evidence available on its effectiveness and predictability in promoting the regeneration of critical size cranio-maxillo-facial defects, the neo-osteogenesis potential and the reconstruction of atrophic alveolar ridges before, or in conjunction with, the placement of dental implants. The authors conclude that future research should focus on (a) the investigation of the molecular mechanisms underlying the wound healing process following GBR application; (b) the identification of site and patient related factors which impact on the effectiveness and predictability of GBR therapy and (c) the evaluation of the pathophysiology of the GBR healing process in the presence of systemic conditions potentially affecting the skeletal system.

  16. Electrical potentials in bone induced by ultrasound irradiation in the megahertz range

    NASA Astrophysics Data System (ADS)

    Okino, M.; Coutelou, S.; Mizuno, K.; Yanagitani, T.; Matsukawa, M.

    2013-09-01

    Low frequency mechanical studies have reported the contribution of stress-induced electrical potentials to bone metabolism. However, the healing mechanism of bone fractures by low intensity ultrasound is not yet clear. We demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. Electrical potentials were obtained from the output of bovine cortical bone transducers. In the range of 0.7-2.5 MHz, sensitivities of bone transducers were around 1/1000 of a poly (vinylidene fluoride) ultrasonic transducer and did not depend on magnitude and alignment of hydroxyapatite crystallites in bone.

  17. Space Nutrition: Effects on Bone and Potential Nutrition Countermeasures

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2008-01-01

    Optimal nutrition will be critical for crew members who embark on space exploration missions. Nutritional assessment provides an opportunity to ensure that crewmembers begin their missions in optimal nutritional status, to document changes during a mission and , if necessary, to provide intervention to maintain that status throughout the mission, and to assesses changes after landing in order to facilitate the return to their normal status as soon as possible after landing. We report here the findings from our nutritional assessment of the US astronauts who participated in the first eight International Space Station (ISS) missions. Bone loss during space flight remains one of the most critical challenges to astronaut health on space exploration missions. An increase in bone resorption of ISS crew members after flight was indicated by several markers. Vitamin D status also remains a challenge for long-duration space travelers, who lack ultraviolet light exposure in the shielded craft. Many nutrients affect bone, including calcium, protein, fatty acids, sodium, and others. Data supporting their potential as countermeasures for space flight, as published in many papers, will be reviewed in this presentation. Defining nutrient requirements, and being able to provide and maintain those nutrients on exploration missions, will be critical for maintaining crew member health. Please note, this abstract is not required for the meeting. A presentation on the topics described above will be given. This abstract is for travel documentation only.

  18. Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases.

    PubMed

    Zhang, Qian; Chen, Bin; Yan, Fuhua; Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

  19. Diffusion of Protease into Meat & Bone Meal for Solubility Improvement and Potential Inactivation of the BSE Prion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Government-imposed feed bans have created a need for new applications for meat & bone meal (MBM). Many potential new applications require MBM protein to be both soluble and free of infectious prion. Treatment with protease is generally effective in reducing insoluble, thermally-denatured proteins t...

  20. Wnt signaling in bone formation and its therapeutic potential for bone diseases

    PubMed Central

    Kim, Jeong Hwan; Liu, Xing; Wang, Jinhua; Chen, Xiang; Zhang, Hongyu; Kim, Stephanie H.; Cui, Jing; Li, Ruidong; Zhang, Wenwen; Kong, Yuhan; Zhang, Jiye; Shui, Wei; Lamplot, Joseph; Rogers, Mary Rose; Zhao, Chen; Wang, Ning; Rajan, Prashant; Tomal, Justin; Statz, Joseph; Wu, Ningning; Luu, Hue H.; Haydon, Rex C.

    2013-01-01

    The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3β, has also been reported to stimulate osteogenesis by stabilizing β catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential. PMID:23514963

  1. Preparation and characterization of an iron oxide-hydroxyapatite nanocomposite for potential bone cancer therapy.

    PubMed

    Sneha, Murugesan; Sundaram, Nachiappan Meenakshi

    2015-01-01

    Recently, multifunctional magnetic nanostructures have been found to have potential applications in biomedical and tissue engineering. Iron oxide nanoparticles are biocompatible and have distinctive magnetic properties that allow their use in vivo for drug delivery and hyperthermia, and as T2 contrast agents for magnetic resonance imaging. Hydroxyapatite is used frequently due to its well-known biocompatibility, bioactivity, and lack of toxicity, so a combination of iron oxide and hydroxyapatite materials could be useful because hydroxyapatite has better bone-bonding ability. In this study, we prepared nanocomposites of iron oxide and hydroxyapatite and analyzed their physicochemical properties. The results suggest that these composites have superparamagnetic as well as biocompatible properties. This type of material architecture would be well suited for bone cancer therapy and other biomedical applications.

  2. In Vitro Characterization of Human Mesenchymal Stem Cells Isolated from Different Tissues with a Potential to Promote Complex Bone Regeneration

    PubMed Central

    Matula, Zsolt; Szigeti, Anna; Várady, György; Szalma, József; Szabó, Gyula; Uher, Ferenc; Sarkadi, Balázs; Német, Katalin

    2016-01-01

    Bone tissue regeneration is a major, worldwide medical need, and several strategies have been developed to support the regeneration of extensive bone defects, including stem cell based bone grafts. In addition to the application of stem cells with high osteogenic potential, it is important to maintain proper blood flow in a bone graft to avoid inner graft necrosis. Mesenchymal stem cells (MSCs) may form both osteocytes and endothelial cells; therefore we examined the combined in vitro osteogenic and endothelial differentiation capacities of MSCs derived from adipose tissue, Wharton's jelly, and periodontal ligament. Based on a detailed characterization presented here, MSCs isolated from adipose tissue and periodontal ligament may be most appropriate for generating vascularized bone grafts. PMID:27999599

  3. Micro-CT evaluation of bone defects: applications to osteolytic bone metastases, bone cysts, and fracture.

    PubMed

    Buie, Helen R; Bosma, Nick A; Downey, Charlene M; Jirik, Frank R; Boyd, Steven K

    2013-11-01

    Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Spmax) by 72.8%. Regression modeling revealed SpSD (β=0.974, p<0.0001) to be a significant predictor of the defect volume (R(2)=0.949) and Spmax (β=0.712, p<0.0001) and SpSD (β=0.271, p=0.022) to be significant predictors of the defect diameter (R(2)=0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone.

  4. Quantum walk and potential application

    NASA Astrophysics Data System (ADS)

    Wang, J. B.; Douglas, B. L.

    2010-06-01

    Quantum walk represents a generalised version of the well-known classical random walk. Regardless of their apparent connection, the dynamics of quantum walk is often non-intuitive and far deviate from its classical counterpart. However, despite such potentially superior efficiency in quantum walks, it has yet to be applied to problems of practical importance. In this paper, we will give a brief introduction to quantum walks and discuss potential applications.

  5. Synthesis and Characterization of Protein-Conjugated Silver Nanoparticles/Silver Salt Loaded Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) Film for Prevention of Bacterial Infections and Potential Use in Bone Tissue Engineering Applications

    NASA Astrophysics Data System (ADS)

    Bakare, Rotimi Ayotunde

    concentration (0.19and 0.31 microg) compared to commercially available gentamicin and sulfamethoxazole/trimethoprim which showed sometimes selective antimicrobial activity and antimicrobial activity at high concentration (10 microg and 23.75/1.25 microg/disc). Additionally, a clear zone of inhibition around AgCl/PHBV composite film was noticed on a modified Kirby-Bauer disk diffusion assay. Optical density results and colony forming unit measurements showed that AgCl/PHBV composite film exhibit broad bactericidal activity. Next, we evaluated the cytotoxicity of Ag/BSA nanoparticles loaded collagen immobilized PHBV films and AgCl/PHBV composite films towards MC3T3-E1 cells at the same concentration both films showed broad antimicrobial activity. By using MTT assay, we established that Ag/BSA nanoparticles loaded collagen immobilized PHBV film showed minimal, if any, cytotoxic effect towards MC3T3-E1 cells while AgCl/PHBV composite film showed significant cytotoxic effect compared to tissue culture polystyrene. Our research findings provide several formulations for preparation of scaffold, if properly tuned; it can be used as a potential biocompatible and biodegradable scaffold for the prevention of bacterial infections and promotion of cell attachment and proliferation in bone tissue engineering applications.

  6. Novel applications of statins for bone regeneration

    PubMed Central

    Shah, Sarita R.; Werlang, Caroline A.; Kasper, F. Kurtis; Mikos, Antonios G.

    2015-01-01

    The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering. PMID:26543666

  7. Development of electrospun bone-mimetic matrices for bone regenerative applications

    NASA Astrophysics Data System (ADS)

    Phipps, Matthew Christopher

    Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein show that BMMs supported great-er adhesion, proliferation, and integrin activation of mesenchymal stem cells (MSCs), the multipotent bone-progenitor cells within bone marrow and the periosteum, in comparison to electrospun PCL alone. These cellular responses, which are essential early steps in the process of bone regeneration, highlight the benefits of presenting cells with natural bone molecules. Subsequently, evaluation of new bone formation in a rat cortical tibia defect showed that BMMs are highly osteoconductive. However, these studies also revealed the inability of endogenous cells to migrate within electrospun matrices due to the inherently small pore sizes. To address this limitation, which will negatively impact the rate of scaf-fold-to-bone turnover and inhibit vascularization, sacrificial fibers were added to the ma-trix. The removal of these fibers after fabrication resulted in BMMs with larger pores, leading to increased infiltration of MSCs and endogenous bone cells. Lastly, we evaluat-ed the potential of our matrices to stimulate the recruitment of MSCs, a vital step in bone healing, through the sustained delivery of platelet derived growth factor-BB (PDGF-BB). BMMs were found to adsorb and subsequently release greater

  8. 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.

  9. Potential therapeutic applications of biosurfactants.

    PubMed

    Gudiña, Eduardo J; Rangarajan, Vivek; Sen, Ramkrishna; Rodrigues, Lígia R

    2013-12-01

    Biosurfactants have recently emerged as promising molecules for their structural novelty, versatility, and diverse properties that are potentially useful for many therapeutic applications. Mainly due to their surface activity, these molecules interact with cell membranes of several organisms and/or with the surrounding environments, and thus can be viewed as potential cancer therapeutics or as constituents of drug delivery systems. Some types of microbial surfactants, such as lipopeptides and glycolipids, have been shown to selectively inhibit the proliferation of cancer cells and to disrupt cell membranes causing their lysis through apoptosis pathways. Moreover, biosurfactants as drug delivery vehicles offer commercially attractive and scientifically novel applications. This review covers the current state-of-the-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications.

  10. Applications of carbon nanomaterials in bone tissue engineering.

    PubMed

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

    2014-10-01

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

  11. Vibration therapy: clinical applications in bone

    PubMed Central

    Thompson, William R.; Yen, Sherwin S.; Rubin, Janet

    2015-01-01

    Purpose of review The musculoskeletal system is largely regulated through dynamic physical activity and is compromised by cessation of physical loading. There is a need to recreate the anabolic effects of loading on the musculoskeletal system, especially in frail individuals who cannot exercise. Vibration therapy is designed to be a nonpharmacological analogue of physical activity, with an intention to promote bone and muscle strength. Recent findings Animal and human studies suggest that high-frequency, low-magnitude vibration therapy improves bone strength by increasing bone formation and decreasing bone resorption. There is also evidence that vibration therapy is useful in treating sarcopenia, which confounds skeletal fragility and fall risk in aging. Enhancement of skeletal and muscle strength involves regulating the differentiation of mesenchymal stem cells to build these tissues; mesenchymal stem cell lineage allocation is positively promoted by vibration signals. Summary Vibration therapy may be useful as a primary treatment as well as an adjunct to both physical and pharmacological treatments, but future studies must pay close attention to compliance and dosing patterns, and importantly, the vibration signal, be it low-intensity vibration (<1g) appropriate for treatment of frail individuals or high-intensity vibration (>1g) marketed as a training exercise. PMID:25354044

  12. Bone poroelasticity.

    PubMed

    Cowin, S C

    1999-03-01

    Poroelasticity is a well-developed theory for the interaction of fluid and solid phases of a fluid-saturated porous medium. It is widely used in geomechanics and has been applied to bone by many authors in the last 30 years. The purpose of this work is, first, to review the literature related to the application of poroelasticity to the interstitial bone fluid and, second, to describe the specific physical and modeling considerations that establish poroelasticity as an effective and useful model for deformation-driven bone fluid movement in bone tissue. The application of poroelasticity to bone differs from its application to soft tissues in two important ways. First, the deformations of bone are small while those of soft tissues are generally large. Second, the bulk modulus of the mineralized bone matrix is about six times stiffer than that of the fluid in the pores while the bulk moduli of the soft tissue matrix and the pore water are almost the same. Poroelasticity and electrokinetics can be used to explain strain-generated potentials in wet bone. It is noted that strain-generated potentials can be used as an effective tool in the experimental study of local bone fluid flow, and that the knowledge of this technique will contribute to the answers of a number of questions concerning bone mineralization, osteocyte nutrition and the bone mechanosensory system.

  13. Exploration of electric properties of bone compared to cement: streaming potential and piezoelectirc properties

    NASA Astrophysics Data System (ADS)

    Dry, Carolyn

    2015-03-01

    Bone is a material after which to model construction materials for many reasons, including its great strength, toughness, and adaptability. This paper focuses on bone's intrinsic ability to adapt to its environment, namely loading conditions. Research on bone's electrical properties reveals that two phenomena occur in bone to allow it to adapt to environmental changes; they are the inherent piezoelectric property of bone and the streaming potential of bone [1]. Together they create charge differences that attract ions to specific regions of the bone, namely those under greatest stress, in order to build up the region to handle the applied load. Research on the utilization of these properties in cement in order to increase adaptability was studied along with 1) the inherent electric properties of the cement itself and 2) considered the introduction of a different polymer or ceramic within the cement to impart piezoelectricity and streaming potential.

  14. Bone grafts.

    PubMed

    Hubble, Matthew J W

    2002-09-01

    Bone grafts are used in musculoskeletal surgery to restore structural integrity and enhance osteogenic potential. The demand for bone graft for skeletal reconstruction in bone tumor, revision arthroplasty, and trauma surgery, couple with recent advances in understanding and application of the biology of bone transplantation, has resulted in an exponential increase in the number of bone-grafting procedures performed over the last decade. It is estimated that 1.5 million bone-grafting procedures are currently performed worldwide each year, compared to a fraction of that number 20 years ago. Major developments also have resulted in the harvesting, storage, and use of bone grafts and production of graft derivatives, substitutes, and bone-inducing agents.

  15. The Use of Total Human Bone Marrow Fraction in a Direct Three-Dimensional Expansion Approach for Bone Tissue Engineering Applications: Focus on Angiogenesis and Osteogenesis

    PubMed Central

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

    2015-01-01

    Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion. PMID:25333855

  16. Physiological mechanisms and therapeutic potential of bone mechanosensing

    PubMed Central

    Xiao, Zhousheng

    2016-01-01

    Skeletal loading is an important physiological regulator of bone mass. Theoretically, mechanical forces or administration of drugs that activate bone mechanosensors would be a novel treatment for osteoporotic disorders, particularly age-related osteoporosis and other bone loss caused by skeletal unloading. Uncertainty regarding the identity of the molecular targets that sense and transduce mechanical forces in bone, however, has limited the therapeutic exploitation of mechanosesning pathways to control bone mass. Recently, two evolutionally conserved mechanosensing pathways have been shown to function as “physical environment” sensors in cells of the osteoblasts lineage. Indeed, polycystin–1 (Pkd1, or PC1) and polycystin–2 (Pkd2, or PC2, or TRPP2), which form a flow sensing receptor channel complex, and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1), which responds to the extracellular matrix microenvironment act in concert to reciprocally regulate osteoblastogenesis and adipogenesis through co-activating Runx2 and a co-repressing PPARγ activities. Interactions of polycystins and TAZ with other putative mechanosensing mechanism, such as primary cilia, integrins and hemichannels, may create multifaceted mechanosensing networks in bone. Moreover, modulation of polycystins and TAZ interactions identify novel molecular targets to develop small molecules that mimic the effects of mechanical loading on bone. PMID:26038304

  17. Application of ultrasound in bone surgery: two case reports.

    PubMed

    Escoda-Francolí, Jaume; Rodríguez-Rodríguez, Araceli; Berini-Aytés, Leonardo; Gay-Escoda, Cosme

    2010-11-01

    The present study describes some of the applications of ultrasound in bone surgery, based on the presentation of two clinical cases. The Piezosurgery® ultrasound device was used (Tecnología Mectron Medical, Carasco, Italy). In one case the instrument was used to harvest a chin bone graft for placement in a bone defect at level 1.2, while in the other case a bony window osteotomy was made in the external wall of the maxillary sinus, in the context of a sinus membrane lift procedure. The Piezosurgery® device produces specific ultrasound frequency modulation (25-29 kHz), and has been designed to secure increased precision in application to bone surgery. This instrument produces selective sectioning of the mineralized bone structures, and causes less intra- and postoperative bleeding. One of the advantages of the Piezosurgery® device is that it can be used for maxillary sinus lift procedures in dental implant placement. In this context it considerably lessens the risk of sinus mucosa laceration by preparing the bony window in the external wall of the upper maxilla, and can be used to complete the lifting maneuver. The use of ultrasound in application to hard tissues can be regarded as a slow technique compared with the conventional rotary instruments, since it requires special surgical skill and involves a certain learning curve.

  18. Potential applications of bacteriorhodopsin mutants

    PubMed Central

    Saeedi, P.; Moosaabadi, J. Mohammadian; Sebtahmadi, S. Sina; Mehrabadi, J. Fallah; Behmanesh, M.; Mekhilef, S.

    2012-01-01

    Bacteriorhodopsin (BR), a model system in biotechnology, is a G-protein dependent trans membrane protein which serves as a light driven proton pump in the cell membrane of Halobacterium salinarum. Due to the linkage of retinal to the protein, it seems colored and has numbers of versatile properties. As in vitro culture of the Halobacteria is very difficult, and isolation is time consuming and usually inefficient, production of genetically modified constructs of the protein is essential. There are three important characteristics based on protein catalytic cycle and molecular functions of photo-electric, photochromic and proton transporting, which makes this protein as a strategic molecule with potential applications in biotechnology. Such applications include protein films, used in artificial retinal implants, light modulators, three-dimensional optical memories, color photochromic sensors, photochromic and electrochromic papers and ink, biological camouflage and photo detectors for biodefense and non-defense purposes. PMID:22895057

  19. Nanostructured surfaces for bone biotemplating applications.

    PubMed

    Popat, Ketul C; Daniels, R Hugh; Dubrow, Robert S; Hardev, Veeral; Desai, Tejal A

    2006-04-01

    A major goal of orthopedic biomaterials research is to design better surface chemistries and configurations to control behavior of bone cells such as osteoblasts. Nanostructured architecture significantly affects the response of several cell lines. In this work, nanostructured surfaces were prepared by vapor liquid solid growth of silicon nanowires from size-controlled gold colloid catalysts deposited on fused silica substrates. The lengths and surface densities of the nanowires were varied to assess the effect of these parameters on bone cell response. Osteoblasts were seeded on nanowire surfaces to investigate both short-term adhesion and proliferation and long-term functionality and matrix production. Cell adhesion and proliferation were characterized using a standard 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and cell counting for up to 4 days of culture. The total protein content, alkaline phosphatase activity, and matrix production were quantified using standard colorimetric assays for up to 4 weeks of culture. Matrix production was also characterized by measuring surface concentrations of calcium and phosphorus using X-ray photoelectron spectroscopy. Further, scanning electron microscopy was used to investigate osteoblast morphology on nanostructured surfaces. Over the 4-week study, the nanostructured surfaces demonstrated improved osteoblast adhesion and proliferation and increased alkaline phosphatase activity and matrix production compared to non-nanostructured control surfaces.

  20. Multi-lineage potential research of bone marrow mesenchymal stem cells from Bama miniature pig.

    PubMed

    Bai, Chunyu; Chen, Shuming; Gao, Yuhua; Shan, Zhiqiang; Guan, Weijun; Ma, Yuehui

    2015-12-01

    Bone marrow mesenchymal stem cells (BMSCs) are easy to obtain and thought to be ideal candidate cells for reconstruction of tissues and organs. Pigs are an appropriate animal model because their physiological structure, organ size, nutritional metabolism, and pathological reactions are similar to those of humans. In this study, bone marrow was collection from Bama miniature pigs to isolate BMSCs (B-BMSCs) by whole bone marrow culture method. We then examined their biological characteristics such as growth kinetics, surface antigen, and multi-lineage potential. B-BMSCs could be cultured for 36 passages in vitro. Growth kinetics and colony forming assay analyses indicated that B-BMSCs had a strong capacity for self-renewal in vitro and their proliferation rate appeared to decrease with passaging. These findings were supported by the animal cytophysiology in vitro. Surface antigen detection showed that B-BMSCs expressed CD29, CD44, CD71, CD73, and CD90, but not the endothelial cell marker CD31 or hematopoietic cell-specific marker CD34. This result was consistent with the characteristics of B-BMSCs. Furthermore, under appropriate conditions for multidirectional differentiation, B-BMSCs were induced to differentiate into adipocytes, osteoblasts, neuron-like cells, islet cells, liver-like cells, and endothelial cells as indicated by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. These results verified the differentiation potential of B-BMSCs. In this study, B-BMSCs were isolated from Bama miniature pigs, and the self-renewal ability and differential potential was evaluated in vitro. The present study has important bearing on the potential application of B-BMSCs as a stem cell source for regenerative therapies. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 671-685, 2015. © 2015 Wiley Periodicals, Inc.

  1. [Bone-length measurement at low back and its application].

    PubMed

    Fang, Jin

    2015-06-01

    By reviewing some acupuncture literature regarding the settings of bone-length measurement at low back, it was found out that ancient and modern descriptions were not consistent. In China current acupuncture textbook, it was mostly described as "the horizontal distance between inner borders of two scapulas was 6 cun". However, after analysis, it was believed that this setting was not reasonable in the clinical application of acupuncture, and it was agreed with the opinion that "midpoint of inner borders of two scapulas when scapulas are in abduction position" should be taken as bone-length measurement of low back. Besides, a self-made bone-length scale was applied to locate acupoint at low back, which could provide references for its standardized application manipulation.

  2. The potential role of free chitosan in bone trauma and bone cancer management.

    PubMed

    Tan, Mei L; Shao, Peng; Friedhuber, Anna M; van Moorst, Mallory; Elahy, Mina; Indumathy, Sivanjah; Dunstan, Dave E; Wei, Yongzhong; Dass, Crispin R

    2014-09-01

    Bone defects caused by fractures or cancer-mediated destruction are debilitating. Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a free drug. We demonstrate that free chitosan promotes osteoblast proliferation and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing of bone fractures with greater trabecular bone formation was observed in mice treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and breast cancer cells via caspase-2 and -3 activation, and reduces their establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour in pregnant mice, but decreases foetal length and changes pancreatic secretory acini. With certain controls in place, chitosan could be useful for bone trauma management.

  3. Osteogenic potential: Comparison between bone marrow and adipose-derived mesenchymal stem cells.

    PubMed

    Liao, Han-Tsung; Chen, Chien-Tzung

    2014-07-26

    Bone tissue engineering (BTE) is now a promising research issue to improve the drawbacks from traditional bone grafting procedure such as limited donor sources and possible complications. Stem cells are one of the major factors in BTE due to the capability of self renewal and multi-lineage differentiation. Unlike embryonic stem cells, which are more controversial in ethical problem, adult mesenchymal stem cells are considered to be a more appropriate cell source for BTE. Bone marrow mesenchymal stem cells (BMSCs) are the earliest-discovered and well-known stem cell source using in BTE. However, the low stem cell yield requiring long expansion time in vitro, pain and possible morbidities during bone marrow aspiration and poor proliferation and osteogenic ability at old age impede its' clinical application. Afterwards, a new stem cell source coming from adipose tissue, so-called adipose-derived stem cells (ASCs), is found to be more suitable in clinical application because of high stem cells yield from lipoaspirates, faster cell proliferation and less discomfort and morbidities during harvesting procedure. However, the osteogenic capacity of ASCs is now still debated because most papers described the inferior osteogenesis of ASCs than BMSCs. A better understanding of the osteogenic differences between ASCs and BMSCs is crucial for future selection of cells in clinical application for BTE. In this review, we describe the commonality and difference between BMSCs and ASCs by cell yield, cell surface markers and multiple-differentiation potential. Then we compare the osteogenic capacity in vitro and bone regeneration ability in vivo between BMSCs and ASCs based on the literatures which utilized both BMSCs and ASCs simultaneously in their articles. The outcome indicated both BMSCs and ASCs exhibited the osteogenic ability to a certain extent both in-vitro and in-vivo. However, most in-vitro study papers verified the inferior osteogenesis of ASCs; conversely, in

  4. Calcium polyphosphate particulates for bone void filler applications.

    PubMed

    Pilliar, Robert M; Kandel, Rita A; Grynpas, Marc D; Theodoropoulos, John; Hu, Youxin; Allo, Bedilu; Changoor, Adele

    2016-02-01

    This study investigates the characteristics of porous calcium polyphosphate particulates (CPPp) formed using two different processing treatments as bone void fillers in non- or minimally load-bearing sites. The two calcium polyphosphate particulate variants (grades) were formed using different annealing conditions during particulate preparation to yield either more slowly degrading calcium polyphosphate particulates (SD-CPPp) or faster degrading particulates (FD-CPPp) as suggested by a previous degradation study conducted in vitro (Hu et al., Submitted for publication 2016). The two CPPp grades were compared as bone void fillers in vivo by implanting particulates in defects created in rabbit femoral condyle sites (critical size defects). The SD-CPPp and FD-CPPp were implanted for 4- and 16-week periods. The in vivo study indicated a significant difference in amount of new bone formed in the prepared sites with SD-CPPp resulting in more new bone formation compared with FD-CPPp. The lower bone formation characteristic of the FD-CPPp was attributed to its faster degradation rate and resulting higher local concentration of released polyphosphate degradation products. The study results indicate the importance of processing conditions on preparing calcium polyphosphate particulates for potential use as bone void fillers in nonload-bearing sites. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  5. Design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite as a potential bone graft substitute material

    NASA Astrophysics Data System (ADS)

    Florschutz, Anthony Vatroslav

    Utilization of bone grafts for the treatment of skeletal pathology is a common practice in orthopaedic, craniomaxillofacial, dental, and plastic surgery. Autogenous bone graft is the established archetype but has disadvantages including donor site morbidity, limited supply, and prolonging operative time. In order to avoid these and other issues, bone graft substitute materials are becoming increasingly prevalent among surgeons for reconstructing skeletal defects and arthrodesis applications. Bone graft substitutes are biomaterials, biologics, and guided tissue/bone regenerative devices that can be used alone or in combinations as supplements or alternatives to autogenous bone graft. There is a growing interest and trend to specialize graft substitutes for specific indications and although there is good rationale for this indication-specific approach, the development and utility of a more universal bone graft substitute may provide a better answer for patients and surgeons. The aim of the present research focuses on the design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite composites for potential use as a bone graft substitutes. After initial establishment of rational material design, gelatinhydroxyapatite scaffolds were fabricated with different gelatin:hydroxyapatite ratios and crosslinking concentrations. The synthesized scaffolds were subsequently evaluated on the basis of their swelling behavior, porosity, density, percent composition, mechanical properties, and morphology and further assessed with respect to cell-biomaterial interaction and biomineralization in vitro. Although none of the materials achieved mechanical properties suitable for structural graft applications, a reproducible material design and synthesis was achieved with properties recognized to facilitate bone formation. Select scaffold formulations as well as a subset of scaffolds loaded with recombinant human bone morphogenetic protein-2 were

  6. Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase.

    PubMed Central

    Kasten, T P; Collin-Osdoby, P; Patel, N; Osdoby, P; Krukowski, M; Misko, T P; Settle, S L; Currie, M G; Nickols, G A

    1994-01-01

    We have examined the effects of modulating nitric oxide (NO) levels on osteoclast-mediated bone resorption in vitro and the effects of nitric oxide synthase (NOS) inhibitors on bone mineral density in vivo. Diaphorase-based histochemical staining for NOS activity of bone sections or highly enriched osteoclast cultures suggested that osteoclasts exhibit substantial NOS activity that may account for basal NO production. Chicken osteoclasts were cultured for 36 hr on bovine bone slices in the presence or absence of the NO-generating agent sodium nitroprusside or the NOS inhibitors N-nitro-L-arginine methyl ester and aminoguanidine. Nitroprusside markedly decreased the number of bone pits and the average pit area in comparison with control cultures. On the other hand, NOS inhibition by N-nitro-L-arginine methyl ester or aminoguanidine dramatically increased the number of bone pits and the average resorption area per pit. In a model of osteoporosis, aminoguanidine potentiated the loss of bone mineral density in ovariectomized rats. Aminoguanidine also caused a loss of bone mineral density in the sham-operated rats. Inhibition of NOS activity in vitro and in vivo resulted in an apparent potentiation of osteoclast activity. These findings suggest that endogenous NO production in osteoclast cultures may regulate resorption activity. The modulation of NOS and NO levels by cells within the bone microenvironment may be a sensitive mechanism for local control of osteoclast bone resorption. Images PMID:7513424

  7. Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases

    PubMed Central

    2014-01-01

    Sclerostin is a small protein expressed by the SOST gene in osteocytes, bone cells that respond to mechanical stress applied to the skeleton and appear to play an important role in the regulation of bone remodeling. When sclerostin binds to its receptors on the cell surface of osteoblasts, a downstream cascade of intracellular signaling is initiated, with the ultimate effect of inhibiting osteoblastic bone formation. Recent studies have shown that the SOST gene is also expressed by articular chondrocytes and that modulation of its activity may have effects on articular cartilage and subchondral bone. The role of sclerostin in the pathogenesis of osteoarthritis in humans has not yet been defined, and the potential utility of treating osteoarthritis with interventions that alter sclerostin is not known. Rare genetic skeletal disorders in humans with low sclerostin levels, such as sclerosteosis and van Buchem disease, have been associated with a high bone mineral density (BMD) phenotype and low risk of fractures. This has led to the concept that antisclerostin interventions might be useful in the treatment of patients with osteoporosis and skeletal disorders associated with low bone mass. Compounds that inhibit sclerostin have been shown to stimulate bone formation and reduce bone resorption, with a robust increase in BMD. Investigational monoclonal antibodies to sclerostin, including romosozumab, blosozumab, and BPS804, have advanced to phase II clinical trials or beyond. If antisclerostin therapy is found to have beneficial effects on clinical endpoints, such as reduction of fracture risk or improvement in quality of life in patients with osteoarthritis, with a favorable balance of benefit and risk, then this class of compounds may become a prominent addition to the options for therapy of osteoporosis and other skeletal disorders. PMID:24688605

  8. Bone loss of vertebral bodies at the operative segment after cervical arthroplasty: a potential complication?

    PubMed

    Heo, Dong Hwa; Lee, Dong Chan; Oh, Jong Yang; Park, Choon Keun

    2017-02-01

    OBJECTIVE Bony overgrowth and spontaneous fusion are complications of cervical arthroplasty. In contrast, bone loss or bone remodeling of vertebral bodies at the operation segment after cervical arthroplasty has also been observed. The purpose of this study is to investigate a potential complication-bone loss of the anterior portion of the vertebral bodies at the surgically treated segment after cervical total disc replacement (TDR)-and discuss the clinical significance. METHODS All enrolled patients underwent follow-up for more than 24 months after cervical arthroplasty using the Baguera C disc. Clinical evaluations included recording demographic data and measuring the visual analog scale and Neck Disability Index scores. Radiographic evaluations included measurements of the functional spinal unit's range of motion and changes such as bone loss and bone remodeling. The grading of the bone loss of the operative segment was classified as follows: Grade 1, disappearance of the anterior osteophyte or small minor bone loss; Grade 2, bone loss of the anterior portion of the vertebral bodies at the operation segment without exposure of the artificial disc; or Grade 3, significant bone loss with exposure of the anterior portion of the artificial disc. RESULTS Forty-eight patients were enrolled in this study. Among them, bone loss developed in 29 patients (Grade 1 in 15 patients, Grade 2 in 6 patients, and Grade 3 in 8 patients). Grade 3 bone loss was significantly associated with postoperative neck pain (p < 0.05). Bone loss was related to the motion preservation effect of the operative segment after cervical arthroplasty in contrast to heterotopic ossification. CONCLUSIONS Bone loss may be a potential complication of cervical TDR and affect early postoperative neck pain. However, it did not affect mid- to long-term clinical outcomes or prosthetic failure at the last follow-up. Also, this phenomenon may result in the motion preservation effect in the operative segment

  9. Potential applications of ocular thermography.

    PubMed

    Morgan, P B; Soh, M P; Efron, N; Tullo, A B

    1993-07-01

    Thermography is an investigative technique which allows rapid color-coded display of the temperature across a wide surface by means of infrared detection. We describe an ocular thermographic study of a normal population and present case studies describing the application of this technique for patients with ocular disease. We found that 95% of the normal population have an interocular temperature difference (temperature of center of right cornea minus temperature of center of left cornea) of 0.60 degrees or less. There appears to be a greater difference in temperature between the limbus and the center of the cornea in patients with dry eyes. This technique has potential for evaluating tear film disorders and inflammatory conditions, for monitoring the progress of such conditions, and for evaluating the efficacy of various treatments.

  10. Application of AMOR in craniofacial rabbit bone bioengineering.

    PubMed

    Freire, Marcelo; Choi, Jeong-Ho; Nguyen, Anthony; Chee, Young Deok; Kook, Joong-Ki; You, Hyung-Keun; Zadeh, Homayoun H

    2015-01-01

    Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models.

  11. AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure.

    PubMed

    Bolam, K A; Galvão, D A; Spry, N; Newton, R U; Taaffe, D R

    2012-12-01

    Androgen suppression treatment (AST) for men with prostate cancer is associated with a number of treatment-related side effects including an accelerated rate of bone loss. This loss of bone is greatest within the first year of AST and increases the risk for fracture. Pharmaceutical treatment in the form of bisphosphonates is currently used to counter the effects of hormone suppression on bone but is costly and associated with potential adverse effects. Recently, exercise has been shown to be an important adjuvant therapy to manage a range of treatment-related toxicities and enhance aspects of quality of life for men receiving AST. We propose that physical exercise may also have an important role in not only attenuating the bone loss associated with AST but in improving bone health and reducing fracture risk. In this review, the rationale underlying exercise as a countermeasure to AST-induced bone loss is provided.

  12. A potential mechanism for allometric trabecular bone scaling in terrestrial mammals

    PubMed Central

    Christen, Patrik; Ito, Keita; van Rietbergen, Bert

    2015-01-01

    Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations. PMID:25655770

  13. A potential mechanism for allometric trabecular bone scaling in terrestrial mammals.

    PubMed

    Christen, Patrik; Ito, Keita; van Rietbergen, Bert

    2015-03-01

    Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations.

  14. Conversations between insulin and bone: Potential mechanism of high bone density in patients with Berardinelli-Seip Congenital Lipodystrophy.

    PubMed

    Lima, Josivan Gomes; Lima, Natalia Nobrega; Nobrega, Lucia Helena C; Jeronimo, Selma Maria B

    2016-12-01

    Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty storing lipid in adipocytes, low body fat, hypertriglyceridemia, and fat liver. The serum leptin is usually very low, and serum insulin, as well as HOMAIR (homeostasis model assessment), is very high and correlated positively with bone mineral density (BMD). Despite deficiency/insufficiency of vitamin D, low body mass index, low daily calcium intake, physical inactivity, and menarche at a later age, BSCL patients usually have normal or even high BMD. We hypothesize that low leptin and high insulin may play a role in this outcome. Understanding the potential pathophysiological mechanism of these bone abnormalities will help to clarify the effects of extreme insulin resistance in the bone.

  15. A new biphasic osteoinductive calcium composite material with a negative Zeta potential for bone augmentation

    PubMed Central

    Smeets, Ralf; Kolk, Andreas; Gerressen, Marcus; Driemel, Oliver; Maciejewski, Oliver; Hermanns-Sachweh, Benita; Riediger, Dieter; Stein, Jamal M

    2009-01-01

    The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC) with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential) which was found to be favorable for bone regeneration and osseointegration of dental implants. PMID:19523239

  16. Collagen type I from bovine bone. Effect of animal age, bone anatomy and drying methodology on extraction yield, self-assembly, thermal behaviour and electrokinetic potential.

    PubMed

    Ferraro, Vincenza; Gaillard-Martinie, Brigitte; Sayd, Thierry; Chambon, Christophe; Anton, Marc; Santé-Lhoutellier, Véronique

    2017-04-01

    Natural collagen is easily available from animal tissues such as bones. Main limitations reported in the use of natural collagen are heterogeneity and loss of integrity during recovery. However, its natural complexity, functionality and bioactivity still remain to be achieved through synthetic and recombinant ways. Variability of physicochemical properties of collagen extracted from bovine bone by acetic acid was then investigated taking into account endogenous and exogenous factors. Endogenous: bovine's bones age (4 and 7 years) and anatomy (femur and tibia); exogenous: thermal treatments (spray-drying and lyophilisation). Scanning electron microscopy, spectroscopy (EDS, FTIR, UV/Vis and CD), differential scanning calorimetry (DSC), centesimal composition, mass spectrometry, amino acids and zeta-potential analysis were used for the purpose. Age correlated negatively with yield of recovery and positively with minerals and proteoglycans content. Comparing the anatomy, higher yields were found for tibias, and higher stability of tibias collagen in solution was noticed. Whatever the age and the anatomy, collagens were able to renature and to self-assemble into tri-dimensional structures. Nonetheless thermal stability and kinetics of renaturation were different. Variability of natural collagen with bone age and anatomy, and drying methodology, may be a crucial advantage to conceive tailor-made applications in either the biological or technical sector.

  17. Insulin-like Growth Factor 2 (IGF-2) Potentiates BMP-9-Induced Osteogenic Differentiation and Bone Formation

    PubMed Central

    Chen, Liang; Jiang, Wei; Huang, Jiayi; He, Bai-Cheng; Zuo, Guo-Wei; Zhang, Wenli; Luo, Qing; Shi, Qiong; Zhang, Bing-Qiang; Wagner, Eric R; Luo, Jinyong; Tang, Min; Wietholt, Christian; Luo, Xiaoji; Bi, Yang; Su, Yuxi; Liu, Bo; Kim, Stephanie H; He, Connie J; Hu, Yawen; Shen, Jikun; Rastegar, Farbod; Huang, Enyi; Gao, Yanhong; Gao, Jian-Li; Zhou, Jian-Zhong; Reid, Russell R; Luu, Hue H; Haydon, Rex C; He, Tong-Chuan; Deng, Zhong-Liang

    2010-01-01

    Efficient osteogenic differentiation and bone formation from mesenchymal stem cells (MSCs) should have clinical applications in treating nonunion fracture healing. MSCs are adherent bone marrow stromal cells that can self-renew and differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. We have identified bone morphogenetic protein 9 (BMP-9) as one of the most osteogenic BMPs. Here we investigate the effect of insulin-like growth factor 2 (IGF-2) on BMP-9-induced bone formation. We have found that endogenous IGF-2 expression is low in MSCs. Expression of IGF-2 can potentiate BMP-9-induced early osteogenic marker alkaline phosphatase (ALP) activity and the expression of later markers. IGF-2 has been shown to augment BMP-9-induced ectopic bone formation in the stem cell implantation assay. In perinatal limb explant culture assay, IGF-2 enhances BMP-9-induced endochondral ossification, whereas IGF-2 itself can promote the expansion of the hypertropic chondrocyte zone of the cultured limb explants. Expression of the IGF antagonists IGFBP3 and IGFBP4 leads to inhibition of the IGF-2 effect on BMP-9-induced ALP activity and matrix mineralization. Mechanistically, IGF-2 is further shown to enhance the BMP-9-induced BMPR-Smad reporter activity and Smad1/5/8 nuclear translocation. PI3-kinase (PI3K) inhibitor LY294002 abolishes the IGF-2 potentiation effect on BMP-9-mediated osteogenic signaling and can directly inhibit BMP-9 activity. These results demonstrate that BMP-9 crosstalks with IGF-2 through PI3K/AKT signaling pathway during osteogenic differentiation of MSCs. Taken together, our findings suggest that a combination of BMP-9 and IGF-2 may be explored as an effective bone-regeneration agent to treat large segmental bony defects, nonunion fracture, and/or osteoporotic fracture. © 2010 American Society for Bone and Mineral Research. PMID:20499340

  18. Potential Role of CD68 in Breast Cancer Bone Metastasis

    DTIC Science & Technology

    2012-01-01

    reliable data. b. Quantify and compare CD68 expression levels in normal mammary epithelial cells, breast cancer tissues from primary sites and breast...cancer tissues from bone metastasis (Months 2-24). I have applied for and obtained the Institutional review board (IRB) approval to proceed with...this portion of the research. I am currently awaiting the normal and diseased tissues from our official collaborator Dr. Hue Luu in the Department of

  19. Native multipotential stromal cell colonization and graft expander potential of a bovine natural bone scaffold.

    PubMed

    Kouroupis, Dimitrios; Baboolal, Thomas G; Jones, Elena; Giannoudis, Peter V

    2013-12-01

    Graft expanders are bone scaffolds used, in combination with autografts, to fill large bone defects in trauma surgery. This study investigates the graft expander potential of a natural bone substitute Orthoss by studying its ability to support attachment, growth and osteogenic differentiation of neighboring multipotential stromal cells (MSCs). Material consisting of bone marrow (BM) aspirate and reamer-irrigator-aspirator (RIA)-harvested autograft bone was co-cultured with commercially available Orthoss granules. Native MSCs attached to Orthoss were expanded and phenotypically characterized. MSCs egress from neighboring cancelous bone was assessed in 3D Matrigel co-cultures. MSC differentiation was evaluated using scanning electron microscopy and measuring alkaline phosphatase (ALP) activity per cell. CD45(+) hematopoietic lineage cells and highly proliferative CD90(+) CD73(+) CD105(+) MSCs preferentially colonized Orthoss granules, over RIA bone chips. MSC colonization was followed by their intrinsic osteogenic differentiation, assessed as mineral deposition and gradual rise in ALP activity, even in the absence of osteogenic stimuli. When in contact with mixed cell populations and RIA chips, Orthoss granules support the attachment, growth and osteogenic differentiation of neighboring MSCs. Therefore, natural bone substitutes similar to Orthoss can be used as void fillers and graft expanders for repairing large bone defects in conjunction with autologous BM aspirates and autografts.

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

    PubMed

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

    2014-09-01

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

  1. Assessment of bone ingrowth potential of biomimetic hydroxyapatite and brushite coated porous E-beam structures.

    PubMed

    Biemond, J Elizabeth; Eufrásio, Tatiane S; Hannink, Gerjon; Verdonschot, Nico; Buma, Pieter

    2011-04-01

    The bone ingrowth potential of biomimetic hydroxyapatite and brushite coatings applied on porous E-beam structure was examined in goats and compared to a similar uncoated porous structure and a conventional titanium plasma spray coating. Specimens were implanted in the iliac crest of goats for a period of 3 (4 goats) or 15 weeks (8 goats). Mechanical implant fixation generated by bone ingrowth was analyzed by a push out test. Histomorphometry was performed to assess the bone ingrowth depth and bone implant contact. The uncoated and hydroxyapatite-coated cubic structure had significantly higher mechanical strength at the interface compared to the Ti plasma spray coating at 15 weeks of implantation. Bone ingrowth depth was significantly larger for the hydroxyapatite- and brushite-coated structures compared to the uncoated structure. In conclusion, the porous E-beam surface structure showed higher bone ingrowth potential compared to a conventional implant surface after 15 weeks of implantation. Addition of a calcium phosphate coating to the E-beam structure enhanced bone ingrowth significantly. Furthermore, the calcium phosphate coating appears to work as an accelerator for bone ingrowth.

  2. A bioactive metallurgical grade porous silicon-polytetrafluoroethylene sheet for guided bone regeneration applications.

    PubMed

    Chadwick, E G; Clarkin, O M; Raghavendra, R; Tanner, D A

    2014-01-01

    The properties of porous silicon make it a promising material for a host of applications including drug delivery, molecular and cell-based biosensing, and tissue engineering. Porous silicon has previously shown its potential for the controlled release of pharmacological agents and in assisting bone healing. Hydroxyapatite, the principle constituent of bone, allows osteointegration in vivo, due to its chemical and physical similarities to bone. Synthetic hydroxyapatite is currently applied as a surface coating to medical devices and prosthetics, encouraging bone in-growth at their surface and improving osseointegration. This paper examines the potential for the use of an economically produced porous silicon particulate-polytetrafluoroethylene sheet for use as a guided bone regeneration device in periodontal and orthopaedic applications. The particulate sheet is comprised of a series of microparticles in a polytetrafluoroethylene matrix and is shown to produce a stable hydroxyapatite on its surface under simulated physiological conditions. The microstructure of the material is examined both before and after simulated body fluid experiments for a period of 1, 7, 14 and 30 days using Scanning Electron Microscopy. The composition is examined using a combination of Energy Dispersive X-ray Spectroscopy, Thin film X-ray diffraction, Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy and the uptake/release of constituents at the fluid-solid interface is explored using Inductively Coupled Plasma-Optical Emission Spectroscopy. Microstructural and compositional analysis reveals progressive growth of crystalline, 'bone-like' apatite on the surface of the material, indicating the likelihood of close bony apposition in vivo.

  3. The application of induced pluripotent stem cells for bone regeneration: current progress and prospects.

    PubMed

    Teng, Songsong; Liu, Chaoxu; Krettek, Christian; Jagodzinski, Michael

    2014-08-01

    Loss of healthy bone tissue and dysosteogenesis are still common and significant problems in clinics. Cell-based therapy using mesenchymal stem cells (MSCs) has been performed in patients for quite some time, but the inherent drawbacks of these cells, such as the reductions in proliferation rate and osteogenic differentiation potential that occur with aging, greatly limit their further application. Moreover, embryonic stem cells (ESCs) have brought new hope to osteoregenerative medicine because of their full pluripotent differentiation potential and excellent performance in bone regeneration. However, the ethical issues involved in destroying human embryos and the immune reactions that occur after transplantation are two major stumbling blocks impeding the clinical application of ESCs. Instead, induced pluripotent stem cells (iPSCs), which are ESC-like pluripotent cells that are reprogrammed from adult somatic cells using defined transcription factors, are considered a more promising source of cells for regenerative medicine because they present no ethical or immunological issues. Here, we summarize the primary technologies for generating iPSCs and the biological properties of these cells, review the current advances in iPSC-based bone regeneration and, finally, discuss the remaining challenges associated with these cells, particularly safety issues and their potential application for osteoregenerative medicine.

  4. Present status and future potential of enhancing bone healing using nanotechnology.

    PubMed

    Stylios, George; Wan, Taoyu; Giannoudis, Peter

    2007-03-01

    An overview of the current state of tissue engineering material systems used in bone healing is presented. A variety of fabrication processes have been developed that have resulted in porous implant substrates that can address unresolved clinical problems. The merits of these biomaterial systems are evaluated in the context of the mechanical properties and biomedical performances most suitable for bone healing. An optimal scaffold for bone tissue engineering applications should be biocompatible and act as a 3D template for in vitro and in vivo bone growth; in addition, its degradation products should be non-toxic and easily excreted by the body. To achieve these features, scaffolds must consist of an interconnected porous network of micro- and nanoscale to allow extensive body fluid transport through the pores, which will trigger bone ingrowth, cell migration, tissue ingrowth, and eventually vascularization.

  5. Hyaluronic-Acid-Hydroxyapatite Colloidal Gels Combined with Micronized Native ECM as Potential Bone Defect Fillers.

    PubMed

    Dennis, S Connor; Whitlow, Jonathan; Detamore, Michael S; Kieweg, Sarah L; Berkland, Cory J

    2017-01-10

    One of the grand challenges in translational regenerative medicine is the surgical placement of biomaterials. For bone regeneration in particular, malleable and injectable colloidal gelsare frequently designed to exhibit self-assembling and shear-response behavior which facilitates biomaterial placement in tissue defects. The current study demonstrated that by combining native extracellular matrix (ECM) microparticles, i.e., demineralized bone matrix (DBM) and decellularized cartilage (DCC), with hyaluronic acid (HA) and hydroxyapatite (HAP) nanoparticles, a viscoelastic colloidal gel consisting exclusively of natural materials was achieved. Rheological testing of HA-ECM suspensions and HA-HAP-ECM colloidal gels concluded either equivalent or substantially higher storage moduli (G' ≈ 100-10 000 Pa), yield stresses (τy ≈ 100-1000 Pa), and viscoelastic recoveries (G'recovery ≥ 87%) in comparison with controls formulated without ECM, which indicated a previously unexplored synergy in fluid properties between ECM microparticles and HA-HAP colloidal networks. Notable rheological differences were observed between respective DBM and DCC formulations, specifically in HA-HAP-DBM mixtures, which displayed a mean 3-fold increase in G' and a mean 4-fold increase in τy from corresponding DCC mixtures. An initial in vitro assessment of these potential tissue fillers as substrates for cell growth revealed that all formulations of HA-ECM and HA-HAP-ECM showed no signs of cytotoxicity and appeared to promote cell viability. Both DBM and DCC colloidal gels represent promising platforms for future studies in bone and cartilage tissue engineering. Overall, the current study identified colloidal gels constructed exclusively of natural materials, with viscoelastic properties that may facilitate surgical placement for a wide variety of therapeutic applications.

  6. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  7. Fabrication and characterization of a novel carbon fiber-reinforced calcium phosphate silicate bone cement with potential osteo-inductivity.

    PubMed

    Zheng, Jiangjiang; Xiao, Yu; Gong, Tianxing; Zhou, Shuxin; Troczynski, Tom; Yang, Quanzu; Bao, Chongyun; Xu, Xiaoming

    2015-12-23

    The repair of bone defects is still a pressing challenge in clinics. Injectable bone cement is regarded as a promising material to solve this problem because of its special self-setting property. Unfortunately, its poor mechanical conformability, unfavorable osteo-genesis ability and insufficient osteo-inductivity seriously limit its clinical application. In this study, novel experimental calcium phosphate silicate bone cement reinforced by carbon fibers (CCPSC) was fabricated and characterized. First, a compressive strength test and cell culture study were carried out. Then, the material was implanted into the femoral epiphysis of beagle dogs to further assess its osteo-conductivity using a micro-computed tomography scan and histological analysis. In addition, we implanted CCPSC into the beagles' intramuscular pouches to perform an elementary investigation of its osteo-inductivity. The results showed that incorporation of carbon fibers significantly improved its mechanical properties. Meanwhile, CCPSC had better biocompatibility to activate cell adhesion as well as proliferation than poly-methyl methacrylate bone cement based on the cell culture study. Moreover, pronounced biodegradability and improved osteo-conductivity of CCPSC could be observed through the in vivo animal study. Finally, a small amount of osteoid was found at the heterotopic site one month after implantation which indicated potential osteo-inductivity of CCPSC. In conclusion, the novel CCPSC shows promise as a bioactive bone substitute in certain load-bearing circumstances.

  8. Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation.

    PubMed

    Minardi, Silvia; Corradetti, Bruna; Taraballi, Francesca; Sandri, Monica; Van Eps, Jeffrey; Cabrera, Fernando J; Weiner, Bradley K; Tampieri, Anna; Tasciotti, Ennio

    2015-09-01

    Augmentation of regenerative osteogenesis represents a premier clinical need, as hundreds of thousands of patients are left with insufficient healing of bony defects related to a host of insults ranging from congenital abnormalities to traumatic injury to surgically-induced deficits. A synthetic material that closely mimics the composition and structure of the human osteogenic niche represents great potential to successfully address this high demand. In this study, a magnesium-doped hydroxyapatite/type I collagen scaffold was fabricated through a biologically-inspired mineralization process and designed to mimic human trabecular bone. The composition of the scaffold was fully characterized by XRD, FTIR, ICP and TGA, and compared to human bone. Also, the scaffold microstructure was evaluated by SEM, while its nano-structure and nano-mechanical properties were evaluated by AFM. Human bone marrow-derived mesenchymal stem cells were used to test the in vitro capability of the scaffold to promote osteogenic differentiation. The cell/scaffold constructs were cultured up to 7 days and the adhesion, organization and proliferation of the cells were evaluated. The ability of the scaffold to induce osteogenic differentiation of the cells was assessed over 3 weeks and the correlate gene expression for classic genes of osteogenesis was assessed. Finally, when tested in an ectopic model in rabbit, the scaffold produced a large volume of trabecular bone in only two weeks, that subsequently underwent maturation over time as expected, with increased mature cortical bone formation, supporting its ability to promote bone regeneration in clinically-relevant scenarios. Altogether, these results confirm a high level of structural mimicry by the scaffold to the composition and structure of human osteogenic niche that translated to faster and more efficient osteoinduction in vivo--features that suggest such a biomaterial may have great utility in future clinical applications where bone

  9. Minerals and vitamins in bone health: the potential value of dietary enhancement.

    PubMed

    Bonjour, Jean-Philippe; Guéguen, Léon; Palacios, Cristina; Shearer, Martin J; Weaver, Connie M

    2009-06-01

    Nutrition is important to bone health, and a number of minerals and vitamins have been identified as playing a potential role in the prevention of bone diseases, particularly osteoporosis. Despite this, there is currently no consensus on maximum levels to allow in food or as dietary supplements. The benefits of supplementation of populations at risk of osteoporosis with Ca and vitamin D are well established. Prolonged supplementation of Ca and vitamin D in elderly has been shown to prevent bone loss, and in some intervention studies to prevent fragility fractures. Although P is essential to bone health, the average intake is considered to be more than sufficient and supplementation could raise intake to adverse levels. The role of vitamin K in bone health is less well defined, though it may enhance the actions of Ca and vitamin D. Sr administered in pharmacological doses as the ranelate salt was shown to prevent fragility fractures in postmenopausal osteoporosis. However, there is no hard evidence that supplementation with Sr salts would be beneficial in the general population. Mg is a nutrient implicated in bone quality, but the benefit of supplementation via foodstuffs remains to be established. A consensus on dietary supplementation for bone health should balance the risks, for example, exposure of vulnerable populations to values close to maximal tolerated doses, against evidence for benefits from randomised clinical trials, such as those for Ca and vitamin D. Feedback from community studies should direct further investigations and help formulate a consensus on dietary supplementation for bone health.

  10. [Application status of rapid prototyping technology in artificial bone based on reverse engineering].

    PubMed

    Fang, Ao; Zheng, Min; Fan, Ding

    2015-02-01

    Artificial bone replacement has made an important contribution to safeguard human health and improve the quality of life. The application requirements of rapid prototyping technology based on reverse engineering in individualized artificial bone with individual differences are particularly urgent. This paper reviewed the current research and applications of rapid prototyping and reverse engineering in artificial bone. The research developments and the outlook of bone kinematics and dynamics simulation are also introduced.

  11. Heating or freezing bone. Effects on angiogenesis induction and growth potential in mice.

    PubMed

    Leunig, M; Yuan, F; Berk, D A; Gerweck, L E; Jain, R K

    1996-08-01

    We have characterized the effect of bone graft treatment by heating or freezing (with or without dimethyl sulfoxide (DMSO)). Tissue culture and dorsal skin-fold chambers in mice were used as sites to quantify the effect on angiogenesis, growth and calcification of neonatal femora. Fresh femora increased in both length and cartilage diameter (calcification in vivo only), but cryopreservation or heating abolished the increase in femoral dimensions. In vivo, femora of all experimental groups elicited an angiogenic response from the host tissue, which was most pronounced for fresh femora, weaker for DMSO-preserved frozen bone and poor for unprotected frozen bone and boiled femora. Freezing in the presence of a cryopreservative (DMSO) was found to preserve the angiogenic potential of frozen bone, whereas unprotected heating or freezing significantly impaired angiogenesis induction and growth potential.

  12. Application of high resolution pQCT analysis for the assessment of a bone lesion: a technical note.

    PubMed

    Rubinacci, A; Tresoldi, D; Villa, I; Rizzo, G; Gaudio, D; De Angelis, D; Gibelli, D; Cattaneo, C

    2015-01-01

    Peripheral quantitative computed tomography (pQCT) has found new fields of application in bone medicine, but none of them concerns the forensic practice. This study exposes the potential of pQCT applied to a penetrating lesion in a vertebral body. A pQCT scanner was used for the measurements (XCT Research SA+; Stratec Medizintechnik GmbH, Pforzheim, Germany). A more precise reconstruction of the path of the lesion within the trabecular bone was reached, with more details concerning the morphological characteristics of the lesion inside the vertebral body, and the elaboration of a 3D model was created, which allowed the operator to define the volume of the lack of tissues related to the lesion. The application of pQCT scan proved to be a potentially useful tool for the assessment of bone lesions, although further studies are needed in order to verify its applicability to forensic context.

  13. Reinforced Portland cement porous scaffolds for load-bearing bone tissue engineering applications.

    PubMed

    Higuita-Castro, Natalia; Gallego-Perez, Daniel; Pelaez-Vargas, Alejandro; García Quiroz, Felipe; Posada, Olga M; López, Luis E; Sarassa, Carlos A; Agudelo-Florez, Piedad; Monteiro, Fernando J; Litsky, Alan S; Hansford, Derek J

    2012-02-01

    Modified Portland cement porous scaffolds with suitable characteristics for load-bearing bone tissue engineering applications were manufactured by combining the particulate leaching and foaming methods. Non-crosslinked polydimethylsiloxane was evaluated as a potential reinforcing material. The scaffolds presented average porosities between 70 and 80% with mean pore sizes ranging from 300 μm up to 5.0 mm. Non-reinforced scaffolds presented compressive strengths and elastic modulus values of 2.6 and 245 MPa, respectively, whereas reinforced scaffolds exhibited 4.2 and 443 MPa, respectively, an increase of ∼62 and 80%. Portland cement scaffolds supported human osteoblast-like cell adhesion, spreading, and propagation (t = 1-28 days). Cell metabolism and alkaline phosphatase activity were found to be enhanced at longer culture intervals (t ≥ 14 days). These results suggest the possibility of obtaining strong and biocompatible scaffolds for bone repair applications from inexpensive, yet technologically advanced materials such as Portland cement.

  14. Potential medical applications of TAE

    NASA Technical Reports Server (NTRS)

    Fahy, J. Ben; Kaucic, Robert; Kim, Yongmin

    1986-01-01

    In cooperation with scientists in the University of Washington Medical School, a microcomputer-based image processing system for quantitative microscopy, called DMD1 (Digital Microdensitometer 1) was constructed. In order to make DMD1 transportable to different hosts and image processors, we have been investigating the possibility of rewriting the lower level portions of DMD1 software using Transportable Applications Executive (TAE) libraries and subsystems. If successful, we hope to produce a newer version of DMD1, called DMD2, running on an IBM PC/AT under the SCO XENIX System 5 operating system, using any of seven target image processors available in our laboratory. Following this implementation, copies of the system will be transferred to other laboratories with biomedical imaging applications. By integrating those applications into DMD2, we hope to eventually expand our system into a low-cost general purpose biomedical imaging workstation. This workstation will be useful not only as a self-contained instrument for clinical or research applications, but also as part of a large scale Digital Imaging Network and Picture Archiving and Communication System, (DIN/PACS). Widespread application of these TAE-based image processing and analysis systems should facilitate software exchange and scientific cooperation not only within the medical community, but between the medical and remote sensing communities as well.

  15. [Therapeutic potential of bone marrow stem cells in cerebral infarction].

    PubMed

    Sánchez-Cruz, Gilberto; Milián-Rodríguez, Lismary

    2015-05-16

    Introduccion. Las celulas madre constituyen una alternativa terapeutica que se encuentra en fase de experimentacion para el infarto cerebral. Objetivo. Mostrar la evidencia cientifica existente sobre el potencial terapeutico de las celulas madre de la medula osea en esta enfermedad. Desarrollo. El infarto cerebral representa el 80% de las enfermedades cerebrovasculares. La trombolisis constituye la unica terapia aprobada, pero, por su estrecha ventana terapeutica, solo se aplica a un bajo porcentaje de los pacientes. De manera alternativa, los tratamientos neurorrestauradores, como el de celulas madre, pueden aplicarse en periodos mas prolongados. Por esta razon se efectuo una busqueda bibliografica en PubMed con el empleo de las palabras clave 'stem cells', 'bone marrow derived mononuclear cells' y 'stroke'. Se encontraron evidencias de seguridad y eficacia de dichas celulas en diferentes momentos evolutivos del infarto cerebral. Se identificaron estudios que en clinica y preclinica las recolectaron por puncion medular y en sangre periferica, y las trasplantaron directamente en el area infartada o por via intravascular. El efecto terapeutico se relaciona con sus propiedades de plasticidad celular y liberacion de factores troficos. Conclusiones. El concentrado de celulas mononucleares autologas, obtenido en sangre periferica o por puncion de la medula osea, y trasplantado por via intravenosa, es una factible opcion metodologica que permitira rapidamente incrementar el numero de ensayos clinicos en diferentes etapas evolutivas del infarto cerebral. Esta terapia muestra seguridad y eficacia; sin embargo, deben ampliarse las evidencias que avalen su generalizacion en humanos.

  16. Moderate alcohol consumption and increased bone mineral density: potential ethanol and non-ethanol mechanisms.

    PubMed

    Jugdaohsingh, R; O'Connell, M A; Sripanyakorn, S; Powell, J J

    2006-08-01

    Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol-bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

  17. Biological Events in Periodontal Ligament and Alveolar Bone Associated with Application of Orthodontic Forces

    PubMed Central

    Feller, L.; Khammissa, R. A. G.; Schechter, I.; Thomadakis, G.; Fourie, J.; Lemmer, J.

    2015-01-01

    Orthodontic force-induced stresses cause dynamic alterations within the extracellular matrix and within the cytoskeleton of cells in the periodontal ligament and alveolar bone, mediating bone remodelling, ultimately enabling orthodontic tooth movement. In the periodontal ligament and alveolar bone, the mechanically induced tensile strains upregulate the expression of osteogenic genes resulting in bone formation, while mechanically induced compressive strains mediate predominantly catabolic tissue changes and bone resorption. In this review article we summarize some of the currently known biological events occurring in the periodontal ligament and in the alveolar bone in response to application of orthodontic forces and how these facilitate tooth movement. PMID:26421314

  18. Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases.

    PubMed

    Suzuki, Nobuo; Somei, Masanori; Seki, Azusa; Reiter, Russel J; Hattori, Atsuhiko

    2008-10-01

    Several reports indicate that melatonin is involved in the regulation of bone metabolism. To examine the direct effect of melatonin on osteoclasts and osteoblasts, we developed an in vitro assay using fish scales that contain osteoclasts, osteoblasts, and bone matrix, all of which are similar to those found in mammalian membrane bone. Using the assay, we demonstrated that melatonin suppressed osteoclastic and osteoblastic activities. These findings are in agreement with the reports from in vivo studies in mice and rats. In an attempt to develop molecules that increase bone mass, novel bromomelatonin derivatives were synthesized, and the effects of these chemicals on osteoclasts and osteoblasts using the scale assay were examined. As a result, novel bromomelatonin derivatives with the ability to possibly increase bone formation were identified. In scale osteoclasts, particularly, 1-benzyl-2,4,6-tribromomelatonin had a more potent activity than melatonin. In reference to osteoblasts, this agent (10(-9)-10(-6)M) significantly activated osteoblasts. The effect of 1-benzyl-2,4,6-tribromomelatonin on bone formation was confirmed in ovariectomized rats. Thus, the oral administration of 1-benzyl-2,4,6-tribromomelatonin augmented the total bone mineral density of the femoral metaphysis of ovariectomized rats. The stress-strain index of the diaphysis in 1-benzyl-2,4,6-tribromomelatonin-treated rats significantly increased in comparison with that in ovariectomized rats. In rats fed a low-calcium diet, the total bone mineral density of the femoral metaphysis significantly increased following the oral administration of 1-benzyl-2,4,6-tribromomelatonin. These studies identified a melatonin derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.

  19. Synchrotron imaging techniques for bone and cartilage tissue engineering: potential, current trends, and future directions.

    PubMed

    Olubamiji, Adeola Deborah; Izadifar, Zohreh; Chen, Daniel Xiongbiao

    2014-10-01

    Biomedical imaging is crucial to the success of bone/cartilage tissue engineering (TE) by providing detailed three-dimensional information on tissue-engineered scaffolds and associated bone/cartilage growth during the healing process. Synchrotron radiation (SR)-based biomedical imaging is an emerging technique for this purpose that has been drawing considerable recent attention. Due to the unique properties of synchrotron light, SR biomedical imaging can provide information that conventional X-ray imaging is not able to capture. SR biomedical imaging techniques notably differ from conventional imaging in both physics and implementation, thus varying with regard to both capability and popularity for biomedical imaging applications. In the earlier decade, synchrotron-based imaging was used in bone/cartilage TE to characterize bone/cartilage scaffolds and tissues as well as the varying degrees of success in reconstruction. However, several key issues should be addressed through research before SR biomedical imaging can be advanced to a noninvasive method for application to live animals and eventually to human patients. This review briefly presents recent developments in this area, focusing on different synchrotron-based biomedical imaging techniques and their advantages and limitations, as well as reported applications to bone and cartilage TE. Key issues and challenges are also identified and discussed along with recommendations for future research.

  20. Corals and Their Potential Applications to Integrative Medicine

    PubMed Central

    Cooper, Edwin L.; Hirabayashi, Kyle; Strychar, Kevin B.; Sammarco, Paul W.

    2014-01-01

    Over the last few years, we have pursued the use and exploitation of invertebrate immune systems, most notably their humoral products, to determine what effects their complex molecules might exert on humans, specifically their potential for therapeutic applications. This endeavor, called “bioprospecting,” is an emerging necessity for biomedical research. In order to treat the currently “untreatable,” or to discover more efficient treatment modalities, all options and potential sources must be exhausted so that we can provide the best care to patients, that is, proceed from forest and ocean ecosystems through the laboratory to the bedside. Here, we review current research findings that have yielded therapeutic benefits, particularly as derived from soft and hard corals. Several applications have already been demonstrated, including anti-inflammatory properties, anticancer properties, bone repair, and neurological benefits. PMID:24757491

  1. Increased bone formation in a rabbit long-bone defect model after single local and single systemic application of erythropoietin.

    PubMed

    Omlor, Georg W; Kleinschmidt, Kerstin; Gantz, Simone; Speicher, Anja; Guehring, Thorsten; Richter, Wiltrud

    2016-08-01

    Background and purpose - Delayed bone healing with non-union is a common problem. Further options to increase bone healing together with surgery are needed. We therefore evaluated a 1-dose single application of erythropoietin (EPO), applied either locally to the defect or systemically during surgery, in a critical-size rabbit long-bone defect. Material and methods - 19 New Zealand White rabbits received a 15-mm defect in the radius diaphysis. An absorbable gelatin sponge was soaked with saline (control group and systemic treatment group) or EPO (local treatment group) and implanted into the gap. The systemic treatment group received EPO subcutaneously. In vivo micro-CT analysis was performed 4, 8, and 12 weeks postoperatively. Vascularization was evaluated histologically. Results - Semiquantitative histomorphometric and radiological evaluation showed increased bone formation (2.3- to 2.5-fold) in both treatment groups after 12 weeks compared to the controls. Quantitative determination of bone volume and tissue volume showed superior bone healing after EPO treatment at all follow-up time points, with the highest values after 12 weeks in locally treated animals (3.0- to 3.4-fold). More vascularization was found in both EPO treatment groups. Interpretation - Initial single dosing with EPO was sufficient to increase bone healing substantially after 12 weeks of follow-up. Local application inside the defect was most effective, and it can be administered directly during surgery. Apart from effects on ossification, systemic and local EPO treatment leads to increased callus vascularization.

  2. Increased bone formation in a rabbit long-bone defect model after single local and single systemic application of erythropoietin

    PubMed Central

    Omlor, Georg W; Kleinschmidt, Kerstin; Gantz, Simone; Speicher, Anja; Guehring, Thorsten; Richter, Wiltrud

    2016-01-01

    Background and purpose Delayed bone healing with non-union is a common problem. Further options to increase bone healing together with surgery are needed. We therefore evaluated a 1-dose single application of erythropoietin (EPO), applied either locally to the defect or systemically during surgery, in a critical-size rabbit long-bone defect. Material and methods 19 New Zealand White rabbits received a 15-mm defect in the radius diaphysis. An absorbable gelatin sponge was soaked with saline (control group and systemic treatment group) or EPO (local treatment group) and implanted into the gap. The systemic treatment group received EPO subcutaneously. In vivo micro-CT analysis was performed 4, 8, and 12 weeks postoperatively. Vascularization was evaluated histologically. Results Semiquantitative histomorphometric and radiological evaluation showed increased bone formation (2.3- to 2.5-fold) in both treatment groups after 12 weeks compared to the controls. Quantitative determination of bone volume and tissue volume showed superior bone healing after EPO treatment at all follow-up time points, with the highest values after 12 weeks in locally treated animals (3.0- to 3.4-fold). More vascularization was found in both EPO treatment groups. Interpretation Initial single dosing with EPO was sufficient to increase bone healing substantially after 12 weeks of follow-up. Local application inside the defect was most effective, and it can be administered directly during surgery. Apart from effects on ossification, systemic and local EPO treatment leads to increased callus vascularization. PMID:27348783

  3. Processing and characterization of diatom nanoparticles and microparticles as potential source of silicon for bone tissue engineering.

    PubMed

    Le, Thi Duy Hanh; Bonani, Walter; Speranza, Giorgio; Sglavo, Vincenzo; Ceccato, Riccardo; Maniglio, Devid; Motta, Antonella; Migliaresi, Claudio

    2016-02-01

    Silicon plays an important role in bone formation and maintenance, improving osteoblast cell function and inducing mineralization. Often, bone deformation and long bone abnormalities have been associated with silica/silicon deficiency. Diatomite, a natural deposit of diatom skeleton, is a cheap and abundant source of biogenic silica. The aim of the present study is to validate the potential of diatom particles derived from diatom skeletons as silicon-donor materials for bone tissue engineering applications. Raw diatomite (RD) and calcined diatomite (CD) powders were purified by acid treatments, and diatom microparticles (MPs) and nanoparticles (NPs) were produced by fragmentation of purified diatoms under alkaline conditions. The influence of processing on the surface chemical composition of purified diatomites was evaluated by X-ray photoelectron spectroscopy (XPS). Diatoms NPs were also characterized in terms of morphology and size distribution by transmission electron microscopy (TEM) and Dynamic light scattering (DLS), while diatom MPs morphology was analyzed by scanning electron microscopy (SEM). Surface area and microporosity of the diatom particles were evaluated by nitrogen physisorption methods. Release of silicon ions from diatom-derived particles was demonstrated using inductively coupled plasma optical emission spectrometry (ICP/OES); furthermore, silicon release kinetic was found to be influenced by diatomite purification method and particle size. Diatom-derived microparticles (MPs) and nanoparticles (NPs) showed limited or no cytotoxic effect in vitro depending on the administration conditions.

  4. Potential applications of satellite navigation

    NASA Astrophysics Data System (ADS)

    Schaenzer, G.

    The applicability of Navstar GPS to civil air navigation is discussed. The accuracy of current air-navigation systems is reviewed; the basic principle and accuracy of GPS navigation are characterized; the relatively low cost of GPS receiving equipment is pointed out; and particular attention is given to hybrid systems combining GPS with inertial navigation. It is predicted that CAT III landings will be possible using such hybrid systems when the GPS satellites are fully deployed, even without access to the military GPS code. Techniques for GPS-based precision landings, reduced-noise landings, landings on parallel runways, control of taxiing maneuvers, and aircraft-based geodetic measurements are briefly described and illustrated with diagrams.

  5. Investigating the Potential of Amnion-Based Scaffolds as a Barrier Membrane for Guided Bone Regeneration.

    PubMed

    Li, Wuwei; Ma, Guowu; Brazile, Bryn; Li, Nan; Dai, Wei; Butler, J Ryan; Claude, Andrew A; Wertheim, Jason A; Liao, Jun; Wang, Bo

    2015-08-11

    Guided bone regeneration is a new concept of large bone defect therapy, which employs a barrier membrane to afford a protected room for osteogenesis and prevent the invasion of fibroblasts. In this study, we developed a novel barrier membrane made from lyophilized multilayered acellular human amnion membranes (AHAM). After decellularization, the AHAM preserved the structural and biomechanical integrity of the amnion extracellular matrix (ECM). The AHAM also showed minimal toxic effects when cocultured with mesenchymal stem cells (MSCs), as evidenced by high cell density, good cell viability, and efficient osteogenic differentiation after 21-day culturing. The effectiveness of the multilayered AHAM in guiding bone regeneration was evaluated using an in vivo rat tibia defect model. After 6 weeks of surgery, the multilayered AHAM showed great efficiency in acting as a shield to avoid the invasion of the fibrous tissues, stabilizing the bone grafts and inducing the massive bone growth. We hence concluded that the advantages of the lyophilized multilayered AHAM barrier membrane are as follows: preservation of the structural and mechanical properties of the amnion ECM, easiness for preparation and handling, flexibility in adjusting the thickness and mechanical properties to suit the application, and efficiency in inducing bone growth and avoiding fibrous tissues invasion.

  6. Biomechanical properties of an advanced new carbon/flax/epoxy composite material for bone plate applications.

    PubMed

    Bagheri, Zahra S; El Sawi, Ihab; Schemitsch, Emil H; Zdero, Rad; Bougherara, Habiba

    2013-04-01

    This work is part of an ongoing program to develop a new carbon fiber/flax/epoxy (CF/flax/epoxy) hybrid composite material for use as an orthopaedic long bone fracture plate, instead of a metal plate. The purpose of this study was to evaluate the mechanical properties of this new novel composite material. The composite material had a "sandwich structure", in which two thin sheets of CF/epoxy were attached to each outer surface of the flax/epoxy core, which resulted in a unique structure compared to other composite plates for bone plate applications. Mechanical properties were determined using tension, three-point bending, and Rockwell hardness tests. Also, scanning electron microscopy (SEM) was used to characterize the failure mechanism of specimens in tension and three-point bending tests. The results of mechanical tests revealed a considerably high ultimate strength in both tension (399.8MPa) and flexural loading (510.6MPa), with a higher elastic modulus in bending tests (57.4GPa) compared to tension tests (41.7GPa). The composite material experienced brittle catastrophic failure in both tension and bending tests. The SEM images, consistent with brittle failure, showed mostly fiber breakage and fiber pull-out at the fractured surfaces with perfect bonding at carbon fibers and flax plies. Compared to clinically-used orthopaedic metal plates, current CF/flax/epoxy results were closer to human cortical bone, making the material a potential candidate for use in long bone fracture fixation.

  7. Hydroxyapatite nanorod-reinforced biodegradable poly(L-lactic acid) composites for bone plate applications.

    PubMed

    Aydin, Erkin; Planell, Josep A; Hasirci, Vasif

    2011-11-01

    Novel PLLA composite fibers containing hydroxyapatite (HAp) nanorods with or without surface lactic acid grafting were produced by extrusion for use as reinforcements in PLLA-based bone plates. Fibers containing 0-50% (w/w) HAp nanorods, aligned parallel to fiber axis, were extruded. Lactic acid surface grafting of HAp nanorods (lacHAp) improved the tensile properties of composites fibers better than the non-grafted ones (nHAp). Best tensile modulus values of 2.59, 2.49, and 4.12 GPa were obtained for loadings (w/w) with 30% lacHAp, 10% nHAp, and 50% amorphous HAp nanoparticles, respectively. Bone plates reinforced with parallel rows of these composite fibers were molded by melt pressing. The best compressive properties for plates were obtained with nHAp reinforcement (1.31 GPa Young's Modulus, 110.3 MPa compressive strength). In vitro testing with osteoblasts showed good cellular attachment and spreading on composite fibers. In situ degradation tests revealed faster degradation rates with increasing HAp content. To our knowledge, this is the first study containing calcium phosphate-polymer nanocomposite fibers for reinforcement of a biodegradable bone plate or other such implants and this biomimetic design was concluded to have potential for production of polymer-based biodegradable bone plates even for load bearing applications.

  8. Development of bone-like zirconium oxide nanoceramic modified chitosan based porous nanocomposites for biomedical application.

    PubMed

    Bhowmick, Arundhati; Pramanik, Nilkamal; Jana, Piyali; Mitra, Tapas; Gnanamani, Arumugam; Das, Manas; Kundu, Patit Paban

    2017-02-01

    Here, zirconium oxide nanoparticles (ZrO2 NPs) were incorporated for the first time in organic-inorganic hybrid composites containing chitosan, poly(ethylene glycol) and nano-hydroxypatite (CS-PEG-HA) to develop bone-like nanocomposites for bone tissue engineering application. These nanocomposites were characterized by FT-IR, XRD, TEM combined with SAED. SEM images and porosity measurements revealed highly porous structure having pore size of less than 1μm to 10μm. Enhanced water absorption capacity and mechanical strengths were obtained compared to previously reported CS-PEG-HA composite after addition of 0.1-0.3wt% of ZrO2 NPs into these nanocomposites. The mechanical strengths and porosities were similar to that of human spongy bone. Strong antimicrobial effects against gram-negative and gram-positive bacterial strains were also observed. Along with getting low alkalinity pH (7.4) values, similar to the pH of human plasma, hemocompatibility and cytocompatibility with osteoblastic MG-63 cells were also established for these nanocomposites. Addition of 15wt% HA-ZrO2 (having 0.3wt% ZrO2 NPs) into CS-PEG (55:30wt%) composite resulted in greatest mechanical strength, porosity, antimicrobial property and cytocompatibility along with suitable water absorption capacity and compatibility with human pH and blood. Thus, this nanocomposite could serve as a potential candidate to be used for bone tissue engineering.

  9. Functionalized carbon nanotubes for potential medicinal applications.

    PubMed

    Zhang, Yi; Bai, Yuhong; Yan, Bing

    2010-06-01

    Functionalized carbon nanotubes display unique properties that enable a variety of medicinal applications, including the diagnosis and treatment of cancer, infectious diseases and central nervous system disorders, and applications in tissue engineering. These potential applications are particularly encouraged by their ability to penetrate biological membranes and relatively low toxicity. High aspect ratio, unique optical property and the likeness as small molecule make carbon nanotubes an unusual allotrope of element carbon. After functionalization, carbon nanotubes display potentials for a variety of medicinal applications, including the diagnosis and treatment of cancer, infectious diseases and central nervous system disorders, and applications in tissue engineering. These potential applications are particularly encouraged by their ability to penetrate biological membranes and relatively low toxicity.

  10. A potential reference point for assessment of condylar bone marrow of the temporomandibular joint on proton density weighted images.

    PubMed

    Yamamoto, Aya; Sano, Tsukasa; Otonari-Yamamoto, Mika; Nishikawa, Keiichi; Kwok, Edmund

    2008-10-01

    The purpose of this research was to determine a potential reference point for measurement of signal intensity of bone marrow of the condyle on proton density-weighted images (PDW) prior to analysis of bone marrow abnormality related to symptomatic osteoarthritis of the temporomandibular joint (TMJ). The study was based on 79 joints in 41 patients. The regions of interest (ROI) were placed over the bone marrow of the condyle and four other structures, It was hypothesized that a correlation between signal intensity of ROI over bone marrow and that of another structure would provide a potential reference point4or measurement of signal intensity of bone marrow. A significant positive linear correlation was found in the group for gray matter-1 and bone marrow. The correlation coefficient was 0.3 (Pearson correlation coefficient; p < 0.05). It was determined that gray matter is a potential reference point in evaluating the signal intensity of bone marrow in the mandibular condyle.

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

    PubMed

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

    2010-07-01

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

  12. Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

    PubMed Central

    King, Tristan J.; Shandala, Tetyana; Lee, Alice M.; Foster, Bruce K.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

    2015-01-01

    Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. PMID:26258775

  13. Aerospace Power Technology for Potential Terrestrial Applications

    NASA Technical Reports Server (NTRS)

    Lyons, Valerie J.

    2012-01-01

    Aerospace technology that is being developed for space and aeronautical applications has great potential for providing technical advances for terrestrial power systems. Some recent accomplishments arising from activities being pursued at the National Aeronautics and Space Administration (NASA) Centers is described in this paper. Possible terrestrial applications of the new aerospace technology are also discussed.

  14. Anabolic potential of bone mineral in human periosteal fibroblasts using steroid markers of healing.

    PubMed

    Suchak, A; Soory, M

    2013-05-01

    A deproteinized natural cancellous bone mineral (B) was studied in a cell culture model for its anabolic potential using two radiolabelled steroid substrates, 14C-testosterone (14C-T) and 14C-4-androstenedione (14C-4-A) independently; in the presence or absence of the anti-androgen finasteride (F) and minocycline (M). Culture medium was assayed for the biologically active metabolite 5 alpha-dihydrotestosterone (DHT) a marker of regenerative potential and wound healing. Confluent monolayer cultures of human periosteal fibroblasts were incubated in Eagle's minimum essential medium with each of the substrates 14C-T and 14C-4-A. Incubations were performed with previously established optimal concentrations of B5 (milligrams/ml), M25 (μg/ml) and F5 (μg/ml) alone and in combination (n=6) for 24h. The eluent was solvent extracted with ethyl acetate (2 ml x 2) and subjected to TLC in a benzene/acetone solvent system (4:1 v/v) for separation of metabolites; they were quantified using a radioisotope scanner. The yield of DHT was increased over controls in response to B and M with both substrates 14C-T and 14C-4-A by 1.7, 1.8-fold and 1.7, 1.6-fold respectively (n=6; p<0.001; one way ANOVA). Combined incubations of B and M resulted in similar yields. F inhibited DHT yields with both radiolabelled substrates by 2-3-fold (n=6; p<0.001) which was overcome by a combined incubation of F+B to values similar to those of controls (p<0.01). Documented pro-anabolic effects of minocycline were applicable as a standard for confirmation of responses to B. Significant increases in yields of DHT in response to B and M with both substrates indicate their anabolic potential in periosteal fibroblasts with implications for wound healing.

  15. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

    NASA Astrophysics Data System (ADS)

    Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

    2016-04-01

    The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has

  16. Collagen based barrier membranes for periodontal guided bone regeneration applications.

    PubMed

    Sheikh, Zeeshan; Qureshi, Javairia; Alshahrani, Abdullah M; Nassar, Heba; Ikeda, Yuichi; Glogauer, Michael; Ganss, Bernhard

    2017-01-01

    Certain cell populations within periodontal tissues possess the ability to induce regeneration, provided they have the opportunity to populate the wound or defect. Guided regeneration techniques have been investigated for regenerating periodontal tissues and such therapies usually utilize barrier membranes. Various natural and synthetic barrier membranes have been fabricated and tested to prevent epithelial and connective tissue cells from invading while allowing periodontal cells to selectively migrate into the defect. This paper focuses on the literature relevant to the use and potential of resorbable collagen membranes in GBR procedures, sites of periodontal and intrabony defects, in cases of socket and alveolar ridge preservation and at implant sites. The results of their use in GBR procedures has shown them to be effective and comparable with non-resorbable membranes with regards to clinical attachment gain, probing depth reduction and defect bone filling. They have also shown to prevent epithelial ingrowth into the defect space during the initial wound healing phase postsurgically. Collagen membranes have also been used for root coverage and GBR procedures and have shown good success rates comparable to subepithelial connective tissue grafts and expanded-polytetrafluoroethylene (e-PTFE) membranes. The future for periodontal tissue engineering is very exciting with the use of barrier membranes expected to continue playing a critical role. However, long-term clinical trials are required to further evaluate and confirm the efficacy of the available collagen barrier membranes for periodontal and bone regeneration use.

  17. Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential

    PubMed Central

    Cicione, Claudia; Muiños-López, Emma; Hermida-Gómez, Tamara; Fuentes-Boquete, Isaac; Díaz-Prado, Silvia; Blanco, Francisco J.

    2013-01-01

    Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions. Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS). Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures. Conclusions. In our experimental conditions, severe hypoxia affects the in vitro differentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed. PMID:24082888

  18. Bone-Forming Capacity and Biodistribution of Bone Marrow-Derived Stromal Cells Directly Loaded Into Scaffolds: A Novel and Easy Approach for Clinical Application of Bone Regeneration.

    PubMed

    Léotot, Julie; Lebouvier, Angélique; Hernigou, Philippe; Bierling, Philippe; Rouard, Hélène; Chevallier, Nathalie

    2015-01-01

    In the context of clinical applications of bone regeneration, cell seeding into scaffolds needs to be safe and easy. Moreover, cell density also plays a crucial role in the development of efficient bone tissue engineering constructs. The aim of this study was to develop and evaluate a simple and rapid cell seeding procedure on hydroxyapatite/β-tricalcium phosphate (HA/βTCP), as well as define optimal cell density and control the biodistribution of grafted cells. To this end, human bone marrow-derived stromal cells (hBMSCs) were seeded on HA/βTCP scaffolds, and we have compared bone formation using an ectopic model. Our results demonstrated a significantly higher bone-forming capacity of hBMSCs directly loaded on HA/βTCP during surgery compared to hBMSCs preseeded for 7 days in vitro on HA/βTCP before ectopic implantation. The extent of new bone formation increases with increasing hBMSC densities quantitatively, qualitatively, and in frequency. Also, this study showed that grafted hBMSCs remained confined to the implantation site and did not spread toward other tissues, such as liver, spleen, lungs, heart, and kidneys. In conclusion, direct cell loading into a scaffold during surgery is more efficient for bone regeneration, as well as quick and safe. Therefore direct cell loading is suitable for clinical requirements and cell production control, making it a promising approach for orthopedic applications. Moreover, our results have provided evidence that the formation of a mature bone organ containing hematopoietic islets needs a sufficiently high local density of grafted hBMSCs, which should guide the optimal dose of cells for clinical use.

  19. Reduction of Dietary Acid Load as a Potential Countermeasure for Bone Loss Associated with Spaceflight

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Watts, S. M.; Sams, C. F.; Whitson, P. A.; Smith, S. M.

    2006-01-01

    In several studies we tested the concepts that diet can alter acid-base balance and that reducing the dietary acid load has a positive effect on maintenance of bone. In study 1, (n = 11, 60-90 d bed rest), the renal acid load of the diet was estimated from its chemical composition, and was positively correlated with urinary markers of bone resorption (P less than 0.05); that is, the greater the acid load, the greater the excretion of bone resorption markers. In study 2, in males (n = 8, 30 d bed rest), an estimate of the ratio of nonvolatile acid precursors to base precursors in the diet was positively correlated (P less than 0.05) with markers of bone resorption. In study 3, for 28 d subjects received either a placebo (n = 6) or an essential amino acid supplement (n = 7) that included methionine, a known acid precursor. During bed rest (28 d), urinary calcium was greater than baseline levels in the supplemented group but not the control group (P less than 0.05), and in the supplemented group, urinary pH decreased (P less than 0.05). In study 4, less bone resorption occurred in space crew members who received potassium citrate (n = 6) during spaceflight of 4-6 months than in crew members who received placebo or were not in the study (n = 8) (P less than 0.05). Reducing acid load has the potential to mitigate increased bone resorption during spaceflight, and may serve as a bone loss countermeasure.

  20. In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease.

    PubMed

    Wang, Yan; Lin, Bo

    2013-07-01

    No anabolic drugs are currently approved to treat multiple myeloma (MM)-induced bone disease and the anti-MM agent bortezomib exhibits the anabolic effects in the clinic. In this study, we focus on investigating potential anabolic treatments of MM-induced bone disease using our previously proposed MM-bone model, with the goal for clarifying the underlying molecular/cellular mechanisms. Firstly, a variety of virtual drug treatments are explored by the parametric study to clarify the anabolic-related molecular/cellular mechanisms. The real drug (i.e., bortezomib) treatments are further examined by developing an integrated model with bortezomib to validate the clarified anabolic-related molecular/cellular mechanisms. The simulated responses to the bortezomib treatments that are validated by the clinical data are consistent with the simulated responses to the virtual drug treatments. Our study clarifies that the anabolic effects in the treatment of MM-induced bone disease are associated with promoting the differentiation of bone marrow stromal cells (BMSC) and inhibiting the apoptosis of active osteoblasts, while promoting the differentiation of osteoblast precursors is instead suggested to be associated with the anti-catabolic effects. Compared with the individual anabolic therapies, the anabolic therapies that promote the differentiation of BMSC in combination with the anti-MM/anti-catabolic therapies are found to induce a greater increase in the bone volume, while the anabolic therapies that inhibit the apoptosis of active osteoblasts in combination with the anti-MM/anti-catabolic therapies induce a lower increase in the bone volume. The simulations also suggest that the direct inhibition of bortezomib on the osteoclast activity is probably a redundant mechanism.

  1. Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.

    PubMed

    Criscitiello, Carmen; Viale, Giulia; Gelao, Lucia; Esposito, Angela; De Laurentiis, Michele; De Placido, Sabino; Santangelo, Michele; Goldhirsch, Aron; Curigliano, Giuseppe

    2015-02-01

    There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called "osteoimmunology". The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival.

  2. Application of synchrotron radiation computed microtomography for quantification of bone microstructure in human and rat bones

    SciTech Connect

    Parreiras Nogueira, Liebert; Barroso, Regina Cely; Pereira de Almeida, Andre; Braz, Delson; Almeida, Carlos Eduardo de; Borba de Andrade, Cherley; Tromba, Giuliana

    2012-05-17

    This work aims to evaluate histomorphometric quantification by synchrotron radiation computed microto-mography in bones of human and rat specimens. Bones specimens are classified as normal and pathological (for human samples) and irradiated and non-irradiated samples (for rat ones). Human bones are specimens which were affected by some injury, or not. Rat bones are specimens which were irradiated, simulating radiotherapy procedures, or not. Images were obtained on SYRMEP beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. The system generated 14 {mu}m tomographic images. The quantification of bone structures were performed directly by the 3D rendered images using a home-made software. Resolution yielded was excellent what facilitate quantification of bone microstructures.

  3. Application of synchrotron radiation computed microtomography for quantification of bone microstructure in human and rat bones

    NASA Astrophysics Data System (ADS)

    Nogueira, Liebert Parreiras; Barroso, Regina Cély; de Almeida, André Pereira; Braz, Delson; de Almeida, Carlos Eduardo; de Andrade, Cherley Borba; Tromba, Giuliana

    2012-05-01

    This work aims to evaluate histomorphometric quantification by synchrotron radiation computed microto-mography in bones of human and rat specimens. Bones specimens are classified as normal and pathological (for human samples) and irradiated and non-irradiated samples (for rat ones). Human bones are specimens which were affected by some injury, or not. Rat bones are specimens which were irradiated, simulating radiotherapy procedures, or not. Images were obtained on SYRMEP beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. The system generated 14 μm tomographic images. The quantification of bone structures were performed directly by the 3D rendered images using a home-made software. Resolution yielded was excellent what facilitate quantification of bone microstructures.

  4. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration.

    PubMed

    Kim, Tae-Hyun; Singh, Rajendra K; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

    2016-04-21

    The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ∼73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.

  5. Potential of mesenchymal stem cells by adenovirus-mediated erythropoietin gene therapy approaches for bone defect.

    PubMed

    Li, Chen; Ding, Jian; Jiang, Liming; Shi, Ce; Ni, Shilei; Jin, Han; Li, Daowei; Sun, Hongchen

    2014-11-01

    Regeneration of large bone defects is a common clinical problem. Recent studies have shown that mesenchymal stem cells (MSCs) have emerged as a promising alternative to traditional surgical techniques. However, it is still a key question how to enhance the osteogenic potential of MSCs for possible clinical trials. The aim of the present study was to investigate the effect of adenovirus-mediated erythropoietin (Ad-EPO) transfer on BMSCs, we performed extensive in vitro/in vivo assays in this study. Flow cytometry analysis and the result of MTT showed that EPO could promote BMSCs proliferation. QPCR data demonstrated that EPO increased expressions of Runx2, Sp7, and Col1 in osteoblast at various time points and also increased alkaline phosphatase activity and the calcium deposition. These results indicate that EPO can increase the differentiation of osteoblast. Importantly, in vivo assays clearly demonstrate that EPO can efficiently induce new bone formation in the bone defect model. Our results strongly suggest that EPO can affect osteoblast differentiation and play important roles in bone regeneration leading to an increase in bone formation.

  6. BMI and BMD: The Potential Interplay between Obesity and Bone Fragility

    PubMed Central

    Palermo, Andrea; Tuccinardi, Dario; Defeudis, Giuseppe; Watanabe, Mikiko; D’Onofrio, Luca; Lauria Pantano, Angelo; Napoli, Nicola; Pozzilli, Paolo; Manfrini, Silvia

    2016-01-01

    Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic. PMID:27240395

  7. Dialkyl bisphosphonate platinum(II) complex as a potential drug for metastatic bone tumor.

    PubMed

    Nakatake, Hidetoshi; Ekimoto, Hisao; Aso, Mariko; Ogawa, Atsushi; Yamaguchi, Asami; Suemune, Hiroshi

    2011-01-01

    Bisphosphonates have high affinity for hydroxyapatite (HA), which is abundantly present in bone. Also, platinum complexes are known that have a wide spectrum of antitumor activities. The conjugate of bisphosphonate and a platinum complex might have HA affinity and antitumor activity, and become a drug for metastatic bone tumor. In this study, the authors synthesized platinum complexes that had dialkyl bisphosphonic acid as a ligand, and evaluated the possibility of the synthesized complexes as a drug for metastatic bone tumor. The synthesized dialkyl bisphosphonate platinum(II) complex was characterized, and its stability in an aqueous solution was also confirmed. The synthesized platinum complex showed higher HA affinity than other platinum complexes such as cisplatin and carboplatin in an experiment of adsorption to HA. In vitro, the platinum complex showed tumor growth inhibitory effect stronger than or equal to cisplatin, which is the most commonly used antitumor agent. Moreover, the platinum complex showed a bone absorption inhibitory effect on the osteoclast. These results suggest potential of dialkyl bisphosphonate platinum(II) complexes as a drug for metastatic bone tumor.

  8. Myogenic Differentiation Potential of Mesenchymal Stem Cells Derived from Fetal Bovine Bone Marrow.

    PubMed

    Okamura, Lucas Hidenori; Cordero, Paloma; Palomino, Jaime; Parraguez, Victor Hugo; Torres, Cristian Gabriel; Peralta, Oscar Alejandro

    2017-03-07

    The myogenic potential of bovine fetal MSC (bfMSC) derived from bone marrow (BM) remains unknown; despite its potential application for the study of myogenesis and its implications for livestock production. In the present study, three protocols for in vitro myogenic differentiation of bfMSC based on the use of DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza), myoblast-secreted factor Galectin-1 (Gal-1), and myoblast culture medium SkGM-2 BulletKit were used. Plastic-adherent bfMSC were isolated from fetal BM collected from abattoir-derived fetuses. Post-thaw viability analyses detected 85.6% bfMSC negative for propidium iodine (PI). Levels of muscle regulatory factors (MRF) MYF5, MYF6, MYOD, and DES mRNA were higher (P < 0.05) in bfMSC cultured under 100 µM of 5-Aza compared to 1 and 10 µM. Treatment of bfMSC with 10 µM of 5-Aza resulted in down-regulation of MYOD mRNA (Days 7 to 21) and up-regulation of MYF6 (Day 7), MYF5, and DES mRNA (Day 21). Gal-1 and SkGM-2 BulletKit induced sequential down-regulation of early MRF (MYF5) and up-regulation of intermediate (MYOD) and late MRF (DES) mRNA. Moreover, DES and MYF5 were immunodetected in differentiated bfMSC. In conclusion, protocols evaluated in bfMSC induced progress into myogenic differentiation until certain extent evidenced by changes in MRF gene expression.

  9. Contribution of SATB2 to the stronger osteogenic potential of bone marrow stromal cells from craniofacial bones.

    PubMed

    Zhang, Ping; Men, Jie; Fu, Yu; Shan, Tengfei; Ye, Jinhai; Wu, Yunong; Tao, Zhenjiang; Liu, Laikui; Jiang, Hongbing

    2012-12-01

    Previous studies have shown that craniofacial bone marrow stromal cells (BMSCs) have a strong osteogenic potential. However, the mechanism by which BMSCs of various embryonic origins develop diverse osteogenic potentials remains unclear. To investigate the mechanisms regulating osteoblast differentiation in two different types of BMSCs, we compared the temporal and spatial mRNA and protein expression patterns of Satb2 and its downstream gene Hoxa2 by using real-time polymerase chain reaction, Western blotting and fluorescent immunostaining in mandible BMSCs (M-BMSCs) and tibia BMSCs (T-BMSCs) undergoing osteoblast differentiation. Higher levels of alkaline phosphatase, greater calcium accumulation and earlier expression of Runx2 were observed in osteogenic-induced M-BMSCs compared with T-BMSCs. Low levels of Satb2 were detected in both types of uninduced BMSCs but the majority of SATB2 was located in the nuclei of M-BMSCs. Notably, Satb2 was expressed earlier in M-BMSCs and Hoxa2, a downstream target of Satb2, was not expressed in uninduced M-BMSCs or during osteoblast differentiation, just as during embryonic mandible development. In contrast, Hoxa2 was reactivated in T-BMSCs during osteoblast differentiation. Based on these results, we conclude that SATB2 plays a different role during osteoblast differentiation of M-BMSCs and T-BMSCs. The earlier activation of Satb2 expression in M-BMSCs compared with T-BMSCs might explain the stronger osteogenic potential of M-BMSCs.

  10. SURGICAL TREATMENT FOR INFECTED LONG BONE DEFECTS AFTER LIMB-THREATENING TRAUMA: APPLICATION OF LOCKED PLATE AND AUTOGENOUS CANCELLOUS BONE GRAFT

    PubMed Central

    KAWAKAMI, RYOICHI; KONNO, SHIN-ICHI; EJIRI, SOICHI; HATASHITA, SATOSHI

    2015-01-01

    ABSTRACT Background: Treatment strategies for bone defects include free bone grafting, distraction osteogenesis, and vascularized bone grafting. Because bone defect morphology is often irregular, selecting treatment strategies may be difficult. With the Masquelet technique, a fracture site is bridged and fixed with a locking plate after treating deep infection with antibiotic-containing cement, and a free cancellous bone-graft is concomitantly placed into the defects. This procedure avoids excessive bone resection. Methods:We studied 6 patients who underwent surgical treatment for deep infection occurring after extremity trauma (2004 through 2009). Ages at surgery ranged from 29 to 59 years (largest age group: 30 s). Mean follow-up was 50.7 months (minimum/maximum: 36/72 months). One patient had complete amputation of the upper extremity, 3 open forearm fractures, 1 closed supracondylar femur fracture, and 1 open tibia fracture. In all patients, bone defects were filled with antibiotic-containing cement beads after infected site debridement. If bacterial culture of infected sites during curettage was positive, surgery was repeated to refill bone defects with antibiotic-containing cement beads. After confirmation of negative bacterial culture, osteosynthesis was performed, in which bone defects were bridged and fixed with locking plates. Concomitantly, crushed cancellous bone grafts harvested from the autogenous ilium was placed in the bone defects. Results: Time from bone grafting and plate fixation to bone union was at least 3 and at most 6 months, 4 months on average. Infection relapsed in one patient with methicillin-resistant Staphylococcus aureus, necessitating vascularized fibular grafting which achieved bone union. No patients showed implant loosening or breakage or infection relapse after the last surgery during follow-up. Conclusion: The advantage of cancellous bone grafting include applicability to relatively large bone defects, simple surgical procedure

  11. Application of K/Sr co-doped calcium polyphosphate bioceramic as scaffolds for bone substitutes.

    PubMed

    Xie, Huixu; Wang, Qianbin; Ye, Qingsong; Wan, Changxiu; Li, Longjiang

    2012-04-01

    Ion doping is one of the most important methods to modify the properties of bioceramics for better biodegrade abilities, biomechanical properties, and biocompatibilities. This paper presents a novel ion doping method applied in calcium polyphosphate (CPP)-based bioceramic scaffolds substituted by potassium and strontium ions (K/Sr) to form (K/Sr-CPP) scaffolds for bone tissue regeneration. The microstructure and crystallization of the scaffolds were detected by scanning electron microscopy and X-ray diffraction. Compressive strength and degradation tests were assessed to evaluate the mechanical and chemical stabilities of K/Sr-CPP in vitro. The cell biocompatibility was measured with respect to the cytotoxicity of the extractions of scaffolds. Muscle pouches and bone implantation were performed to evaluate the biodegradability and osteoconductivity of the scaffolds. The results indicated that the obtained K/Sr-CPP scaffolds had a single beta-CPP phase. The unit cell volume and average grain size increased but the crystallization decreased after the ions were doped into the CPP structure. The K/Sr-CPP scaffolds yielded a higher compressive strength and a better degradation property than the pure CPP scaffold. The MTT assay and in vivo results reveal that the K/Sr-CPP scaffolds exhibited a better cell biocompatibility and a tissue biocompatibility than CPP and hydroxyapatite scaffolds. This study proves the potential applications of K/Sr-CPP scaffolds in bone repair.

  12. Potential Clinical Applications for Spinal Functional MRI

    PubMed Central

    Kornelsen, Jennifer; Mackey, Sean

    2010-01-01

    Functional MRI (fMRI) of the spinal cord is a noninvasive technique for obtaining information regarding spinal cord neuronal function. This article provides a brief overview of recent developments in spinal cord fMRI and outlines potential applications, as well as the limitations that must be overcome, for using spinal fMRI in the clinic. This technique is currently used for research purposes, but significant potential exists for spinal fMRI to become an important clinical tool. PMID:17504642

  13. Fat Layer from Medullary Canal Reamer Aspirate for Potential Use as a Supplemental Osteoinductive Bone Graft Material.

    PubMed

    Sinclair, Sarina S Kay; Horton, C Olsen; Jeray, Kyle J; Tanner, Stephanie L; Burgl, Karen J L

    2015-01-01

    Mesenchymal stem cells (MSCs) are of therapeutic interest to clinicians and researchers, as they have been shown to augment the osteogenic properties of bone grafts. MSCs are known to be prevalent in bone marrow, but are still limited in numbers. Hence, additional sources of MSCs are beneficial to increasing grafting potential. Aspirate material collected using the Reamer/Irrigator/Aspirator (RIA) device (Synthes; Paoli, PA) during reaming of the femoral shaft consists of three main components: bone fragments, liquid flow-through, and a fat layer. Currently, only the bone and liquid layers have been examined for osteoinductive elements, and the bone fragments are exclusively used as autologous bone graft. In the present study, a method to promote cellular outgrowth, tapping proliferative capacity from the previously discarded fatty layer of RIA aspirate, is described. Proliferating cells were successfully isolated from the bone and fatty layers of a consenting patient and found to be viable after liquid nitrogen storage. The osteogenic differentiation potential of the cells isolated from the fat and bone layers was assessed. Cells from both layers of the aspirate expressed statistically significant levels (p < 0.05) of the bone cell marker alkaline phosphatase compared to the control cells, suggesting differentiation along the osteoblastic pathway. Results from this pilot study indicate that the traditionally discarded fatty element of RIA aspirate may be a source of MSCs with bone-forming capabilities and the described isolation technique is effective. Combining the aspirate fatty and bony elements may enhance the clinical success of the RIA autograft.

  14. A case for bone canaliculi as the anatomical site of strain generated potentials

    NASA Technical Reports Server (NTRS)

    Cowin, S. C.; Weinbaum, S.; Zeng, Y.

    1995-01-01

    We address the question of determining the anatomical site that is the source of the experimentally observed strain generated potentials (SGPs) in bone tissue. There are two candidates for the anatomical site that is the SGP source, the collagen-hydroxyapatite porosity and the larger size lacunar-canalicular porosity. In the past it has been argued, on the basis of experimental data and a reasonable model, that the site of the SGPs in bone is the collagen-hydroxyapatite porosity. The theoretically predicted pore radius necessary for the SGPs to reside in this porosity is 16 nm, which is somewhat larger than the pore radii estimated from gas adsorption data where the preponderance of the pores were estimated to be in the range 5-12.5 nm. However, this pore size is significantly larger than the 2 nm size of the small tracer, microperoxidase, which appears to be excluded from the mineralized matrix. In this work a similar model, but one in which the effects of fluid dynamic drag of the cell surface matrix in the bone canaliculi are included, is used to show that it is possible for the generation of SGPs to be associated with the larger size lacunar-canalicular porosity when the hydraulic drag and electrokinetic contribution of the bone fluid passage through the cell coat (glycocalyx) is considered. The consistency of the SGP data with this model is demonstrated. A general boundary condition is introduced to allow for current leakage at the bone surface. The results suggest that the current leakage is small for the in vitro studies in which the strain generated potentials have been measured.

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

    PubMed Central

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

    2016-01-01

    Background: Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. Methods: This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Results: Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Conclusion: Future studies to improve the application of nanomaterials for bone tissue engineering are needed. PMID:28217209

  16. Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing.

    PubMed

    Ying, Zhi-min; Lin, Tiao; Yan, Shi-gui

    2012-12-01

    Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successful anterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. Enhancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return to pre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B) healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis, stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-B healing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulate T-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities in the near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular and molecular levels, describe studies in animal models, and provide a future direction for research.

  17. Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing*

    PubMed Central

    Ying, Zhi-min; Lin, Tiao; Yan, Shi-gui

    2012-01-01

    Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successful anterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. Enhancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return to pre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B) healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis, stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-B healing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulate T-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities in the near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular and molecular levels, describe studies in animal models, and provide a future direction for research. PMID:23225850

  18. Wind erosion potential following application of biosolids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The application of biosolids to agricultural land has the potential to improve soil health and crop production. These benefits could also possibly reduce the threat of wind erosion in arid and semiarid regions. Therefore, we assessed the impact of biosolids on wind erosion of agricultural land at Li...

  19. How tough is bone? Application of elastic-plastic fracture mechanics to bone.

    PubMed

    Yan, Jiahau; Mecholsky, John J; Clifton, Kari B

    2007-02-01

    Bone, with a hierarchical structure that spans from the nano-scale to the macro-scale and a composite design composed of nano-sized mineral crystals embedded in an organic matrix, has been shown to have several toughening mechanisms that increases its toughness. These mechanisms can stop, slow, or deflect crack propagation and cause bone to have a moderate amount of apparent plastic deformation before fracture. In addition, bone contains a high volumetric percentage of organics and water that makes it behave nonlinearly before fracture. Many researchers used strength or critical stress intensity factor (fracture toughness) to characterize the mechanical property of bone. However, these parameters do not account for the energy spent in plastic deformation before bone fracture. To accurately describe the mechanical characteristics of bone, we applied elastic-plastic fracture mechanics to study bone's fracture toughness. The J integral, a parameter that estimates both the energies consumed in the elastic and plastic deformations, was used to quantify the total energy spent before bone fracture. Twenty cortical bone specimens were cut from the mid-diaphysis of bovine femurs. Ten of them were prepared to undergo transverse fracture and the other 10 were prepared to undergo longitudinal fracture. The specimens were prepared following the apparatus suggested in ASTM E1820 and tested in distilled water at 37 degrees C. The average J integral of the transverse-fractured specimens was found to be 6.6 kPa m, which is 187% greater than that of longitudinal-fractured specimens (2.3 kPa m). The energy spent in the plastic deformation of the longitudinal-fractured and transverse-fractured bovine specimens was found to be 3.6-4.1 times the energy spent in the elastic deformation. This study shows that the toughness of bone estimated using the J integral is much greater than the toughness measured using the critical stress intensity factor. We suggest that the J integral method is

  20. Potential teleoperator applications in manned aerospace systems

    NASA Technical Reports Server (NTRS)

    Johnsen, E. G.

    1973-01-01

    The trend of teleoperator development is toward digital computer controlled systems which utilize local sensor-computer-actuator loops to avoid obstacles and to sense manipulator grip-and-slip. The potential applications of advanced teleoperator technology to manned aerospace systems include long manipulator booms to be mounted on the shuttle. These can transfer cargo from the space shuttle and can acquire and retrieve objects in space. Free-flying teleoperators capable of acquiring, inspecting, repairing or refurbishing satellites in orbit are another space application. Another potential application of teleoperator technology is the concept of using an anthropomorphous teleoperator in lieu of man to control aircraft or spacecraft normally controlled by a human pilot.

  1. Bacteriocins: Recent Trends and Potential Applications.

    PubMed

    Bali, Vandana; Panesar, Parmjit S; Bera, Manab B; Kennedy, John F

    2016-01-01

    In the modern era, there is great need for food preservation in both developing and developed countries due to increasing demand for extending shelf life and prevention of spoilage of food material. With the emergence of new pathogens and ability of micro-organisms to undergo changes, exploration of new avenues for the food preservation has gained importance. Moreover, awareness among consumers regarding harmful effects of chemical preservatives has been increased. Globally, altogether there is increasing demand by consumers for chemical-free and minimal processed food products. Potential of bacteriocin and its application in reducing the microbiological spoilages and in the preservation of food is long been recognized. Bacteriocins are normally specific to closely related species without disrupting the growth of other microbial populations. A number of applications of bacteriocin have been reported for humans, live stock, aquaculture etc. This review is focused on recent trends and applications of bacteriocins in different areas in addition to their biopreservative potential.

  2. Towards application of one- and two-dimensional nanomaterials for reinforcement of polymeric nanocomposite bone grafts

    NASA Astrophysics Data System (ADS)

    Farrshid, Behzad

    One- and two-dimensional (1-D and 2-D) nanomaterials possess extraordinary physiochemical properties such as large surface area, excellent mechanical properties, high surface energy and good dispersivity in organic and biological solvents, therefore, they have been extensively used as reinforcing agents to improve the mechanical properties of polymeric scaffolds for bone tissue engineering applications. Carbon nanomaterials such as carbon nanotubes and graphene have been used as reinforcing agents for biodegradable polymeric scaffolds and composites, however, their short- and long-term in vitro cytotoxicity and in vivo biocompatibility is an area of extensive debate. In this study, we have systematically investigated the effects of addition of low concentrations (0.01-0.2 wt. %) of 1-D and 2-D carbon nanomaterials (graphene oxide nanoplatelets, graphene oxide nanoribbons and carbon nanotubes) and inorganic nanomaterials (boron nitride nanotubes, boron nitride nanoplatelers, tungsten disulfide nanotubes and molybdenum disulfide nanoplatelets) on the mechanical properties, cytocompatibility, and bioactivity of poly(propylene fumarate) (PPF) nanocomposites towards their potential applications as porous and nonporous implants for bone tissue engineering. Addition of nanomaterials in the PPF matrix improved the compressive and flexural mechanical properties of non-porous crosslinked PPF nanocomposites and porous PPF scaffolds. Our results suggest that in addition to high surface roughness and surface area of the nanomaterials, the presence of functional groups on the surface of nanomaterials leads to an increased nanomaterial-polymer interaction and a uniform dispersion of nanomaterials in polymer matrix which may be the key factors responsible for an improved mechanical reinforcement. The in vitro studies showed an excellent cytocompatibility for both carbon and inorganic nanomaterial reinforced PPF nanocomposites and scaffolds. Protein adsorption studies and in vitro

  3. 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.

  4. Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors

    PubMed Central

    Solakoglu, Oender; Maierhofer, Christine; Lahr, Georgia; Breit, Elisabeth; Scheunemann, Peter; Heumos, Isabella; Pichlmeier, Uwe; Schlimok, Günter; Oberneder, Ralph; Köllermann, Manfred W.; Köllermann, Jens; Speicher, Michael R.; Pantel, Klaus

    2002-01-01

    Bone marrow is a major homing site for circulating epithelial tumor cells. The present study was aimed to assess the proliferative capacity of occult metastatic cells in bone marrow of patients with operable solid tumors especially with regard to their clinical outcome. We obtained bone marrow aspirates from 153 patients with carcinomas of the prostate (n = 46), breast (n = 45), colon (n = 33), and kidney (n = 29). Most of the patients (87%) had primary disease with no clinical signs of overt metastases [tumor-node-metastasis (TNM)-stage UICC (Union Internationale Contre le Cancer) I-III]. After bone marrow was cultured for 21–102 days under special cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 124 patients (81%). The cultured epithelial cells harbored Ki-ras2 mutations and numerical chromosomal aberrations. The highest median number of expanded tumor cells was observed in prostate cancer (2,619 per flask). There was a significant positive correlation between the number of expanded tumor cells and the UICC-stage of the patients (P = 0.03) or the presence of overt metastases (P = 0.04). Moreover, a strong expansion of tumor cells was correlated to an increased rate of cancer-related deaths (P = 0.007) and a reduced survival of the patients (P = 0.006). In conclusion, the majority of cancer patients have viable tumor cells in their bone marrow at primary tumor diagnosis, and the proliferative potential of these cells determines the clinical outcome. PMID:11854519

  5. Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies

    PubMed Central

    Tawara, Ken; Oxford, Julia T; Jorcyk, Cheryl L

    2011-01-01

    Metastatic events to the bone occur frequently in numerous cancer types such as breast, prostate, lung, and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma. Accumulating evidence suggests that the inflammatory cytokine interleukin (IL)-6 is frequently upregulated and is implicated in the ability of cancer cells to metastasize to bone. IL-6 is able to activate various cell signaling cascades that include the STAT (signal transducer and activator of transcription) pathway, the PI3K (phosphatidylinositol-3 kinase) pathway, and the MAPK (mitogen-activated protein kinase) pathway. Activation of these pathways may explain the ability of IL-6 to mediate various aspects of normal and pathogenic bone remodeling, inflammation, cell survival, proliferation, and pro-tumorigenic effects. This review article will discuss the role of IL-6: 1) in bone metabolism, 2) in cancer metastasis to bone, 3) in cancer prognosis, and 4) as potential therapies for metastatic bone cancer. PMID:21625400

  6. Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

    NASA Astrophysics Data System (ADS)

    Ordikhani, F.; Simchi, A.

    2014-10-01

    Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

  7. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    PubMed

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p < 0.001) for the unweighted metric and not the weighted metric. The members of the bacterial communities were more similar within than between decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted).

  8. Hydroxyapatite-hybridized chitosan/chitin whisker bionanocomposite fibers for bone tissue engineering applications.

    PubMed

    Pangon, Autchara; Saesoo, Somsak; Saengkrit, Nattika; Ruktanonchai, Uracha; Intasanta, Varol

    2016-06-25

    Biomimetic nanofibrous scaffolds derived from natural biopolymers for bone tissue engineering applications require good mechanical and biological performances including biomineralization. The present work proposes the utility of chitin whisker (CTWK) to enhance mechanical properties of chitosan/poly(vinyl alcohol) (CS/PVA) nanofibers and to offer osteoblast cell growth with hydroxyapatite (HA) mineralization. By using diacid as a solvent, electrospun CS/PVA nanofibrous membranes containing CTWK can be easily obtained. The dimension stability of nanofibrous CS/PVA/CTWK bionanocomposite is further controlled by exposing to glutaraldehyde vapor. The nanofibrous membranes obtained allow mineralization of HA in concentrated simulated body fluid resulting in an improvement of Young's modulus and tensile strength. The CTWK combined with HA in bionanocomposite is a key to promote osteoblast cell adhesion and proliferation. The present work, for the first time, demonstrates the use of CTWKs for bionanocomposite fibers of chitosan and its hydroxyapatite biomineralization with the function in osteoblast cell culture. These hydroxyapatite-hybridized CS/PVA/CTWK bionanocomposite fibers (CS/PVA/CTWK-HA) offer a great potential for bone tissue engineering applications.

  9. Neuropeptide y and neuropeptide y y5 receptor interaction restores impaired growth potential of aging bone marrow stromal cells.

    PubMed

    Igura, Koichi; Haider, Husnain Kh; Ahmed, Rafeeq P H; Sheriff, Sulaiman; Ashraf, Muhammad

    2011-08-01

    Abstract improved growth characteristics of the aging bone marrow cells subsequent to neuropeptide Y (NPY)/neuropeptide Y Y5 receptor (NPY Y5R) ligand-receptor interaction. Bone marrow cells were isolated from neonatal (2-3 weeks), young (8-12 weeks), and old (24-28 months) rats on the basis of their preferential adherence to plastic surface. After culturing the cells at initial seeding density of 1×10(4) cells/cm(2), we found that the proliferation potential of bone marrow cells declined with age. Real-time polymerase chain reaction (PCR) and Western blotting showed that bone marrow cells in different age groups constitutively expressed NPY and NPY receptor subtypes (Y1R, Y2R, and Y5R). However, NPY and Y5R expression increased by more than 130-fold and decreased by 28-fold, respectively, in old bone marrow cells as compared to young bone marrow cells. NPY (10 nM) stimulated the proliferation of all bone marrow cells age groups, and their proliferation was blocked by Y5R antagonist. However, the pro-proliferative effect of NPY on old bone marrow cells was weaker than other cell groups due to lower Y5R expression. Y5R gene transfection of old bone marrow cells with subsequent NPY(3-36) (10 nM) treatment significantly increased proliferation of old bone marrow cells (>56%) as compared to green fluorescence protein-transfected control old bone marrow cells. Stimulation of old bone marrow cells by NPY treatment rejuvenated the growth characteristics of aging bone marrow cells as a result of Y5R overexpression.

  10. Hydroxyapatite reinforced with multi-walled carbon nanotubes and bovine serum albumin for bone substitute applications

    NASA Astrophysics Data System (ADS)

    Gholami, Fatemeh; Noor, Ahmad-Fauzi Mohd

    2016-12-01

    The similarity of the chemical composition of HA to the mineral phase of bone and its excellent biocompatibility meets the requirement of materials designed for bone substitute purpose. The application of HA in load bearing devices is limited by its poor mechanical properties. CNTs with outstanding stiffness, strength, combined with their small size and large interfacial area, suggest that they may have great potential as a reinforcing agent for HA. This work aims to develop the Hydroxyapatite/Multi-walled Carbon Nanotubes/Bovine Serum Albumin (HA/MWCNTs/BSA) composites with different types of MWCNTs including hydroxylated and carboxylated MWCNTs (MWCNTs-OH, MWCNTs-COOH), and evaluation of mechanical strength and in vitro cellular response of developed composites. HA powder was mixed with de-ionized water, 15 wt.% BSA, and 0.5 wt.% of different MWCNTs* (> 95%), MWCNTs (> 99.9%), MWCNTs-OH (> 99.9%), MWCNTs-COOH (> 99.9%) to produce composites. Among all developed composites, the HA/MWCNTs-COOH/BSA shows the highest compressive strength (29.57 MPa). The cytotoxic effect of HA/MWCNTs-COOH/BSA with different concentrations (6.25 to 200 µg/ml) was evaluated by MTT assay against normal human colon fibroblast (CCD-18Co cell line). At low concentration, all developed composites were found to be non-cytotoxic when treated to the human fibroblast cells and did not elicit cytotoxic effects on cell proliferation and the highest values of cell viability (283%) for the HA/MWCNTs-COOH/BSA composites obtained; whereas when the concentration was increased, the reduction in cell viability was observed. The novel composites showed favorable cytocompatibility with improved compressive strength which make it applicable to use in range of trabecular bone.

  11. Extremozymes: A Potential Source for Industrial Applications.

    PubMed

    Dumorné, Kelly; Córdova, David Camacho; Astorga-Eló, Marcia; Renganathan, Prabhaharan

    2017-01-20

    Extremophilic microorganisms have established a diversity of molecular strategies in order to survive in extreme conditions. Biocatalysts isolated by these organisms are termed extremozymes, possess extraordinary properties are salt allowance thermostability and cold adaptivity. Extremozymes are very resistant in extreme conditions due to their great solidity and they propose new opportunities for biocatalysis and biotransformations, also for the development of the economy and new line of research through their application. Thermophilic proteins, piezophilic proteins, acidophilic proteins and halophilic proteins have been studied during the last years. Amylases, proteases lipases pullulanases, cellulases, chitinases, xylanases, pectinases isomerases, esterases, dehydrogenases have great potential application for biotechnology such as agricultural, chemical, biomedical and biotechnological processes. The study of extremozymes and their main applications have emerged during the last years.

  12. A model of trabecular bone and an application to osteoporosis

    NASA Astrophysics Data System (ADS)

    Gunaratne, Gemunu H.; Mohanty, Kishore K.; Wimalawansa, Sunil J.

    2002-11-01

    Large bones consists of an outer compact shaft and an inner porous segment, known as the trabecular architecture (TA). The TA is the principal load carrier in bones from older adults, and the aim of therapeutic interventions is to preserve their strength. It is argued that forms for broad-based diagnostic tools for osteoporosis can be identified through an analysis of simple model systems. A model based on elastic networks is introduced, and shows that weak networks can only utilize a small fraction of themselves for stress transmission. This observation is used to argue that the ratio of linear response of a network to DC and AC strain can be used as a surrogate for bone strength. We discuss the possibility of using this measure to identify osteoporotic bone and to monitor the efficacy of therapy.

  13. Differential effects and glucocorticoid potentiation of bone morphogenetic protein action during rat osteoblast differentiation in vitro.

    PubMed

    Boden, S D; McCuaig, K; Hair, G; Racine, M; Titus, L; Wozney, J M; Nanes, M S

    1996-08-01

    Bone morphogenetic proteins (BMPs) induce cartilage and bone differentiation in vivo and promote osteoblast differentiation from calvarial and marrow stromal cell preparations. Functional differences between BMP-2, -4, and -6 are not well understood. Recent investigations find that these three closely related osteoinductive proteins may exert different effects in primary rat calvarial cell cultures, suggesting the possibility of unique functions in vivo. In this study, we use a fetal rat secondary calvarial cell culture system to examine the differential effects of BMP-2, -4, and -6 on early osteoblast differentiation. These cells do not spontaneously differentiate into osteoblasts, as do cells in primary calvarial cultures, but rather require exposure to a differentiation initiator such as glucocorticoid or BMP. We determined that BMP-6 is a 2- to 2.5-fold more potent inducer of osteoblast differentiation than BMP-2 or -4. BMP-6 induced the formation of more and larger bone nodules as well as increased osteocalcin secretion. The effects of all three of these BMPs were potentiated up to 10-fold by cotreatment or pretreatment with the glucocorticoid triamcinolone (Trm). The Trm effects were synergistic with those of BMP-2 or -4, suggesting that this glucocorticoid may increase the cell responsiveness to these BMPs. Finally, BMP-6 did not require either cotreatment or pretreatment with Trm to achieve greater amounts of osteoblast differentiation than seen with BMP-2 or BMP-4 treatment, suggesting that BMP-6 may act at an earlier stage of cell differentiation.

  14. Biomineralization of Natural Collagenous Nanofibrous Membranes and Their Potential Use in Bone Tissue Engineering

    PubMed Central

    Yang, Mingying; Zhou, Guanshan; Castano-Izquierdo, Harold; Zhu, Ye; Mao, Chuanbin

    2015-01-01

    Small intestinal submucosa (SIS) membranes as a decellularized tissue are known to be a natural nanofibrous biomaterial mainly made of type I collagen fibers and containing some growth factors (fibroblast growth factor 2 and transforming growth factor β) desired in tissue engineering. Here we show that the SIS membranes can promote the formation of bone mineral hydroxylapatite (HAP) crystals along the collagen fibers constituting the membranes from a HAP-supersaturated solution. The resultant biomineralized HAP-SIS scaffolds were found to promote the attachment, growth and osteogenic differentiation of mesenchymal stem cells (MSCs) in both basal and osteogenic media by the evaluation of osteogenic marker formation. More importantly, the HAP-SIS scaffolds could induce the osteogenic differentiation in the basal media without osteogenic supplements due to the presence of HAP crystals in the scaffolds. Histological characterization of the MSC-seeded scaffolds showed that HAP-SIS scaffolds are biocompatible and promote the formation of new tissue in vitro. The biomineralized SIS membranes mimic some aspects of natural bone in terms of the composition and nanostructures and can find potential use in bone tissue engineering. PMID:25883539

  15. Orthogonal cutting of cancellous bone with application to the harvesting of bone autograft.

    PubMed

    Malak, Sharif F F; Anderson, Iain A

    2008-07-01

    Autogenous bone graft harvesting results in cell death within the graft and trauma at the donor site. The latter can be mitigated by using minimally invasive tools and techniques, while cell morbidity may be reduced by improving cutter design and cutting parameters. We have performed orthogonal cutting experiments on bovine cancellous bone samples, to gain a basic understanding of the cutting mechanism and to determine design guidelines for tooling. Measurements were performed at cutting speeds from 11.2 to 5000 mm/min, with tool rake angles of 23 degrees, 45 degrees and 60 degrees, and depths of cut in the range of 0.1-3.0 mm. Horizontal and vertical cutting forces were measured, and the chip formation process video recorded. Continuous chip formation was observed for rake angles of 45 degrees and 60 degrees , and depths of cut greater than 0.8 mm. Chip formation for depths of cut greater than 1.0 mm was accompanied by bone marrow extruding out of the free surfaces and away from the rake face. Specific cutting energies decreased with increasing rake angle, increasing depth of cut and increasing cutting speed. Our orthogonal cutting experiments showed that a rake angle of 60 degrees and a depth of cut of 1mm, will avoid excessive fragmentation, keep specific cutting energy low and promote bone marrow extrusion, which may be beneficial for cell survival. We demonstrate how drill bit clearance angle and feed rate can be calculated facilitating a 1mm depth of cut.

  16. Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering

    PubMed Central

    Fernandes, Gabriela; Yang, Shuying

    2016-01-01

    Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors (GFs), it makes stem cells the ideal agents for bone regeneration. Furthermore, platelet-rich plasma (PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future. PMID:28018706

  17. 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

  18. Improvement of osteogenic potential of biphasic calcium phosphate bone substitute coated with synthetic cell binding peptide sequences

    PubMed Central

    Choi, Hyunmin; Park, Nho-Jae; Jamiyandorj, Otgonbold; Hong, Min-Ho; Oh, Seunghan; Park, Young-Bum

    2012-01-01

    Purpose The aim of this study was to evaluate the improvement of osteogenic potential of biphasic calcium phosphate (BCP) bone substitute coated with synthetic cell-binding peptide sequences in a standardized rabbit sinus model. Methods Standardized 6-mm diameter defects were created bilaterally on the maxillary sinus of ten male New Zealand white rabbits, receiving BCP bone substitute coated with synthetic cell binding peptide sequences on one side (experimental group) and BCP bone substitute without coating (control group) on the other side. Histologic and histomorphometric analysis of bone formation was carried out after a healing period of 4 or 8 weeks. Results Histological analysis revealed signs of new bone formation in both experimental groups (4- and 8-week healing groups) with a statistically significant increase in bone formation in the 4-week healing group compared to the control group. However, no statistically significant difference in bone formation was found between the 8-week healing group and the control group. Conclusions This study found that BCP bone substitute coated with synthetic cell-binding peptide sequences enhanced osteoinductive potential in a standardized rabbit sinus model and its effectiveness was greater in the 4-week healing group than in the 8-week healing group. PMID:23185697

  19. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

    PubMed

    Langdahl, Bente; Ferrari, Serge; Dempster, David W

    2016-12-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  20. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis

    PubMed Central

    Langdahl, Bente; Ferrari, Serge; Dempster, David W.

    2016-01-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20–30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  1. Osteogenesis and cytotoxicity of a new Carbon Fiber/Flax/Epoxy composite material for bone fracture plate applications.

    PubMed

    Bagheri, Zahra S; Giles, Erica; El Sawi, Ihab; Amleh, Asma; Schemitsch, Emil H; Zdero, Radovan; Bougherara, Habiba

    2015-01-01

    This study is part of an ongoing program to develop a new CF/Flax/Epoxy bone fracture plate to be used in orthopedic trauma applications. The purpose was to determine this new plate's in-vitro effects on the level of bone formation genes, as well as cell viability in comparison with a medical grade metal (i.e. stainless steel) commonly employed for fabrication of bone plates (positive control). Cytotoxicity and osteogenesis induced by wear debris of the material were assessed using Methyl Tetrazolium (MTT) assay and reverse transcription polymerase chain reaction (RT-PCR) for 3 osteogenesis specific gene markers, including bone morphogenetic proteins (BMP2), runt-related transcription factor 2 (Runx2) and Osterix. Moreover, the Flax/Epoxy and CF/Epoxy composites were examined separately for their wettability properties by water absorption and contact angle (CA) tests using the sessile drop technique. The MTT results for indirect and direct assays indicated that the CF/Flax/Epoxy composite material showed comparable cell viability with no cytotoxicity at all incubation times to that of the metal group (p≥0.05). Osteogenesis test results showed that the expression level of Runx2 marker induced by CF/Flax/Epoxy were significantly higher than those induced by metal after 48 h (p=0.57). Also, the Flax/Epoxy composite revealed a hydrophilic character (CA=68.07°±2.05°) and absorbed more water up to 17.2% compared to CF/Epoxy, which reached 1.25% due to its hydrophobic character (CA=93.22°±1.95°) (p<0.001). Therefore, the new CF/Flax/Epoxy may be a potential candidate for medical applications as a bone fracture plate, as it showed similar cell viability with no negative effect on gene expression levels responsible for bone formation compared to medical grade stainless steel.

  2. Molecular and cellular mechanisms of bone morphogenetic proteins and activins in the skin: potential benefits for wound healing.

    PubMed

    Moura, J; da Silva, L; Cruz, M T; Carvalho, E

    2013-09-01

    Bone morphogenetic proteins (BMPs) and activins are phylogenetically conserved proteins, belonging to the transforming growth factor-β superfamily, that signal through the phosphorylation of receptor-regulated Smad proteins, activating different cell responses. They are involved in various steps of skin morphogenesis and wound repair, as can be evidenced by the fact that their expression is increased in skin injuries. BMPs play not only a role in bone regeneration but are also involved in cartilage, tendon-like tissue and epithelial regeneration, maintain vascular integrity, capillary sprouting, proliferation/migration of endothelial cells and angiogenesis, promote neuron and dendrite formation, alter neuropeptide levels and are involved in immune response modulation, at least in animal models. On the other hand, activins are involved in wound repair through the regulation of skin and immune cell migration and differentiation, re-epithelialization and granulation tissue formation, and also promote the expression of collagens by fibroblasts and modulate scar formation. This review aims at enunciating the effects of BMPs and activins in the skin, namely in skin development, as well as in crucial phases of skin wound healing, such as inflammation, angiogenesis and repair, and will focus on the effects of these proteins on skin cells and their signaling pathways, exploring the potential therapeutic approach of the application of BMP-2, BMP-6 and activin A in chronic wounds, particularly diabetic foot ulcerations.

  3. The potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions.

    PubMed

    Gebert, Carsten; Brinkschmidt, Christian; Bielack, Stefan; Bernhardt, Thomas; Jürgens, Heribert; Böcker, Werner; Winkelmann, Winfried; Bürger, Horst; Gosheger, Georg

    2006-07-01

    Matrix-producing bone lesions consist of a wide variety of benign and malignant conditions. With respect to morphology, an overlap exists between benign and malignant bone tumors that causes difficulties in the final determination of the tumor. This study was conducted to show the potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions. Thirty benign bone tumors were evaluated by conventional comparative genomic hybridization. To test its diagnostic reliability, 5 additional cases were analyzed, all with differential diagnostic difficulties related to morphology and radiology. All were ultimately diagnosed as malignant sarcomas, and unbalanced alterations were detected. In contrast benign tumors or tumor-like lesions did not reveal any chromosomal alterations. Comparative genomic hybridization is a useful adjunct in the complicated differential diagnostic algorithms of matrix-producing bone tumors.

  4. Assessment of age and sex by means of DXA bone densitometry: application in forensic anthropology.

    PubMed

    Castillo, Rafael Fernández; Ruiz, Maria del Carmen López

    2011-06-15

    Today we are witnessing a genuine revolution in diagnostic imaging techniques. Dual X-ray absorptiometry (DEXA) quantifies bone mineral density (BMD) and bone mineral content (BMC). This technique has rarely been used in Forensic Anthropology, although its practical application has been demonstrated by various authors. In this article, we look into the conduct of bone mineral density in the femoral neck, the trochanter, the intertrochanter, the proximal femur and Ward's triangle, in relation to anthropometric age and sex parameters. The research was carried out on 70 persons - 38 men and 32 women - and the results obtained show significant correlations between bone mineral density measurements and anthropometric values. The research demonstrates bone mineral density to be a useful technique for sex and age data in forensic anthropology, particularly in the measurements observed in the Ward's triangle area.

  5. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    PubMed Central

    Asa'ad, Farah; Giannì, Aldo Bruno; Giannobile, William V.; Rasperini, Giulio

    2016-01-01

    To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on “3D-printed” ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration. PMID:27366149

  6. Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold.

    PubMed

    Moshaverinia, Alireza; Chen, Chider; Xu, Xingtian; Akiyama, Kentaro; Ansari, Sahar; Zadeh, Homayoun H; Shi, Songtao

    2014-02-01

    Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD- (arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

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

    NASA Astrophysics Data System (ADS)

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

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

  8. Investigation of immiscible systems and potential applications

    NASA Technical Reports Server (NTRS)

    Markworth, A. J.; Oldfield, W.; Duga, J.; Gelles, S. H.

    1975-01-01

    The droplet coalescence kinetics at 0 g and 1 g were considered for two systems which contained liquid droplets in a host liquid. One of these (Al-In) typified a system containing a liquid phase miscibility gap and the order (oil-water) a mixture of two essentially insoluble liquids. A number of coalescence mechanisms potentially prominent at low g in this system were analyzed and explanations are presented for the observed unusual stability of the emulsion. Ground base experiments were conducted on the coalescence of In droplets in and Al-In alloy during cooling through the miscibility gap at different cooling rates. These were in qualitative agreement with the computer simulation. Potential applications for systems with liquid phase miscibility gaps were explored. Possibilities included superconductors, electrical contact materials, superplastic materials, catalysts, magnetic materials, and others. The role of space processing in their production was also analyzed.

  9. Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications.

    PubMed

    Mir, Rafia; Karim, Sajjad; Kamal, Mohammad Amjad; Wilson, Cornelia M; Mirza, Zeenat

    2016-01-01

    Cone snails, also known as marine gastropods, from Conus genus produce in their venom a diverse range of small pharmacologically active structured peptides called conotoxins. The cone snail venoms are widely unexplored arsenal of toxins with therapeutic and pharmacological potential, making them a treasure trove of ligands and peptidic drug leads. Conotoxins are small disulfide bonded peptides, which act as remarkable selective inhibitors and modulators of ion channels (calcium, sodium, potassium), nicotinic acetylcholine receptors, noradrenaline transporters, N-methyl-D-aspartate receptors, and neurotensin receptors. They are highly potent and specific against several neuronal targets making them valuable as research tools, drug leads and even therapeutics. In this review, we discuss their gene superfamily classification, nomenclature, post-translational modification, structural framework, pharmacology and medical applications of the active conopeptides. We aim to give an overview of their structure and therapeutic potential. Understanding these aspects of conopeptides will help in designing more specific peptidic analogues.

  10. Potential aerospace applications of high temperature superconductors

    NASA Technical Reports Server (NTRS)

    Selim, Raouf

    1994-01-01

    The recent discovery of High Temperature Superconductors (HTS) with superconducting transition temperature, T(sub c), above the boiling point of liquid nitrogen has opened the door for using these materials in new and practical applications. These materials have zero resistance to electric current, have the capability of carrying large currents and as such have the potential to be used in high magnetic field applications. One of the space applications that can use superconductors is electromagnetic launch of payloads to low-earth-orbit. An electromagnetic gun-type launcher can be used in small payload systems that are launched at very high velocity, while sled-type magnetically levitated launcher can be used to launch larger payloads at smaller velocities. Both types of launchers are being studied by NASA and the aerospace industry. The use of superconductors will be essential in any of these types of launchers in order to produce the large magnetic fields required to obtain large thrust forces. Low Temperature Superconductor (LTS) technology is mature enough and can be easily integrated in such systems. As for the HTS, many leading companies are currently producing HTS coils and magnets that potentially can be mass-produced for these launchers. It seems that designing and building a small-scale electromagnetic launcher is the next logical step toward seriously considering this method for launching payloads into low-earth-orbit. A second potential application is the use of HTS to build sensitive portable devices for the use in Non Destructive Evaluation (NDE). Superconducting Quantum Interference Devices (SQUID's) are the most sensitive instruments for measuring changes in magnetic flux. By using HTS in SQUID's, one will be able to design a portable unit that uses liquid nitrogen or a cryocooler pump to explore the use of gradiometers or magnetometers to detect deep cracks or corrosion in structures. A third use is the replacement of Infra-Red (IR) sensor leads on

  11. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs

    PubMed Central

    Lee, Michelle H.; Goralczyk, Anna G.; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A.; Toh, Sue-Anne; Yassin, M. Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

    2016-01-01

    Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced ‘browning’ in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow. PMID:26883894

  12. Chondrogenic Potential of Peripheral Blood Derived Mesenchymal Stem Cells Seeded on Demineralized Cancellous Bone Scaffolds

    PubMed Central

    Wang, Shao-Jie; Jiang, Dong; Zhang, Zheng-Zheng; Huang, Ai-Bing; Qi, Yan-Song; Wang, Hai-Jun; Zhang, Ji-Ying; Yu, Jia-Kuo

    2016-01-01

    As a cell source with large quantity and easy access, peripheral blood mesenchymal stem cells (PBMSCs) were isolated and seeded in porcine demineralized cancellous bone (DCB) scaffolds, cultured in chondrogenic medium and evaluated for in vitro chondrogenesis. Bone marrow MSCs (BMMSCs) and articular cartilage chondrocytes (ACCs) underwent the same process as controls. The morphology, viability and proliferation of PBMSCs in DCB scaffolds were similar to those of BMMSCs and ACCs. PBMSCs and BMMSCs showed similar chondrogenesis potential with consistent production of COL 2 and SOX 9 protein and increased COL 2 and AGC mRNA expressions at week 3 but the COL 2 protein production was still less than that of ACCs. Minimal increase of hypertrophic markers was found in all groups. Relatively higher ALP and lower COL 10 mRNA expressions were found in both MSCs groups at week 3 than that in ACCs, whereas no significant difference of COL 1 and SOX 9 mRNA and MMP 13 protein was found among all groups. To conclude, PBMSCs shared similar proliferation and chondrogenic potential with BMMSCs in DCB scaffolds and could be an alternative to BMMSCs for cartilage tissue engineering. Further optimization of chondrogenesis system is needed regardless of the promising results. PMID:27821864

  13. [Study on the preparation and application of individual artificial bone with carbon/carbon composites].

    PubMed

    Ni, Xinye; Qian, Nong; Zhou, Dong; Miao, Yunliang; Xiong, Xinbo; Lin, Tao; Chen, Da; Zhao, Gongyin; Zhong, Ping

    2013-12-01

    The present paper is aimed to study the preparation and application of individual artificial bone of carbon/carbon composites. Using computer tomography images (CT), we acquired a three-dimensional image. Firstly, we described bone contour line outlined with manual and automatic method by the binary volume data. Secondly, we created 3D object surface information by marching cubes. Finally, we converted this information to non-uniform rational B-spine (NURBS) by using geomagic software. Individual artificial bone with carbon/carbon composite was prepared through the CNC Machining Center. We replaced the humeral head of the tested rabbit, and then observed the effects of implantation in neuroimaging and pathological section. Using this method, we found that the bone shape processed and bone shape replaced was consistent. After implantation, the implant and the surrounding bone tissue bound closely, and bone tissue grew well on the surface of the implant. It has laid a sound foundation of the preparation using this method for individual artificial bone of carbon/carbon composite material.

  14. The in situ mechanics of trabecular bone marrow: the potential for mechanobiological response.

    PubMed

    Metzger, Thomas A; Kreipke, Tyler C; Vaughan, Ted J; McNamara, Laoise M; Niebur, Glen L

    2015-01-01

    Bone adapts to habitual loading through mechanobiological signaling. Osteocytes are the primary mechanical sensors in bone, upregulating osteogenic factors and downregulating osteoinhibitors, and recruiting osteoclasts to resorb bone in response to microdamage accumulation. However, most of the cell populations of the bone marrow niche,which are intimately involved with bone remodeling as the source of bone osteoblast and osteoclast progenitors, are also mechanosensitive. We hypothesized that the deformation of trabecular bone would impart mechanical stress within the entrapped bone marrow consistent with mechanostimulation of the constituent cells. Detailed fluid-structure interaction models of porcine femoral trabecular bone and bone marrow were created using tetrahedral finite element meshes. The marrow was allowed to flow freely within the bone pores, while the bone was compressed to 2000 or 3000 microstrain at the apparent level.Marrow properties were parametrically varied from a constant 400 mPas to a power law rule exceeding 85 Pas. Deformation generated almost no shear stress or pressure in the marrow for the low viscosity fluid, but exceeded 5 Pa when the higher viscosity models were used. The shear stress was higher when the strain rate increased and in higher volume fraction bone. The results demonstrate that cells within the trabecular bone marrow could be mechanically stimulated by bone deformation, depending on deformation rate, bone porosity, and bone marrow properties. Since the marrow contains many mechanosensitive cells, changes in the stimulatory levels may explain the alterations in bone marrow morphology with aging and disease, which may in turn affect the trabecular bone mechanobiology and adaptation.

  15. Comparison of osteogenic potentials of BMP4 transduced stem cells from autologous bone marrow and fat tissue in a rabbit model of calvarial defects.

    PubMed

    Lin, Lin; Shen, Qi; Wei, Xuelei; Hou, Yu; Xue, Tao; Fu, Xin; Duan, Xiaoning; Yu, Changlong

    2009-07-01

    We compared bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) of adult rabbits under identical conditions in terms of their culture characteristics, proliferation capacity, osteogenic differentiation potentials induced by adenovirus-containing bone morphogenetic protein 4 (Ad-BMP4) in vitro, and capacity to repair calvarial defects in the rabbit model by autologous transplantation ex vivo. According to the results of growth curve, cell cycle, and telomerase activity analysis, ADSCs possess a higher proliferation potential. Both of the Ad-BMP4 transduced MSCs expressed BMP4 mRNA and protein and underwent osteogenic differentiation. Up-regulated mRNA expression of all osteogenic genes was observed in differentiated BMSCs and ADSCs, but with different patterns confirmed by real-time RT-PCR. Deposition of calcified extracellular matrix was significantly greater in differentiated ADSCs compared with differentiated BMSCs. X-ray and histological examination indicated significant bone regeneration in the calvarial defects transplanted with Ad-BMP4 transduced autologous MSCs compared to the control groups. There was no significant difference in new bone formation in Ad-BMP4 transduced MSCs based on quantitative digital analysis of histological sections. The use of ADSCs often resulted in the growth of fat tissue structures in the control groups, and the fat tissue structures were not seen with BMSC cells. Our data demonstrate that BMP4 can be potently osteoinductive in vivo, resulting in bone repair. ADSCs may be an attractive alternative to BMSCs for bone tissue engineering under appropriate stimuli. But the easy adipogenic differentiation needs to be considered when choosing adipose tissue for specific clinical application.

  16. The application of nanomaterials in controlled drug delivery for bone regeneration.

    PubMed

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part.

  17. Microdosimetry of astatine-211 using histological images: application to bone marrow.

    PubMed

    Akabani, G; Zalutsky, M R

    1997-12-01

    A method is presented for calculating the small-scale dosimetry of 211At in red bone marrow using chord-length distributions obtained from digitized histological images. This study used histological samples of bone marrow from beagle dogs to convey morphological information about cell conglomerations within bone marrow. Two 211At activity distributions were considered within the extracellular fluid and the surface of red bone marrow cells. Results confirmed the influence of cell conglomeration and activity distribution in determining the microdosimetry of red bone marrow. Average S* values of 1.6 x 10(-9) and 1.90 x 10(-9) Gy g Bq(-1) s(-1) were calculated for activity distributions located within the extracellular fluid and the surface of red bone marrow cells, respectively. The cumulated activity required to reduce survival probability to 0.37 also was calculated as a function of cell sensitivity for both activity distributions. The activity distribution on the cell surface resulted in a higher cell-killing efficiency, requiring a lower activity concentration of approximately 25% when compared with activity located in the extracellular fluid. Of relevance to potential clinical studies with 211At, the probability for zero hits for red bone marrow cells was > 10% for cumulated activities of less than 5.5 x 10(8) Bq s g(-1) in bone marrow.

  18. Comparison of the Osteogenic Potential of OsteoSelect Demineralized Bone Matrix Putty to NovaBone Calcium-Phosphosilicate Synthetic Putty in a Cranial Defect Model

    PubMed Central

    Schallenberger, Mark A.; Rossmeier, Kerri; Lovick, Helena M.; Meyer, Todd R.; Aberman, Harold M.; Juda, Gregory A.

    2014-01-01

    Abstract The purpose of this study was to compare the osteogenic potential of a synthetic and a demineralized bone matrix (DBM) putty using a cranial defect model in New Zealand white rabbits. Paired, bilateral critical-size defects (10 mm) were prepared in the frontal bones of 12 rabbits and filled with either OsteoSelect DBM Putty or NovaBone calcium-phosphosilicate putty. At days 43 and 91, 6 rabbits were killed and examined via semiquantitative histology and quantitative histomorphometry. Defects filled with the DBM putty were histologically associated with less inflammation and fibrous tissue in the defect and more new bone than the synthetic counterpart at both time points. Histomorphometric analysis revealed that the defects filled with DBM putty were associated with significantly more bone formation at day 43 (70.7% vs 40.7%, P = 0.043) and at day 91 (70.4% vs 39.9%, P = 0.0044). The amount of residual implant was similar for both test groups at each time point. PMID:24577306

  19. POTENTIAL THERMOELECTRIC APPLICATIONS IN DIESEL VEHICLES

    SciTech Connect

    Crane, D

    2003-08-24

    Novel thermodynamic cycles developed by BSST provide improvements by factors of approximately 2 in cooling, heating and power generation efficiency of solid-state thermoelectric systems. The currently available BSST technology is being evaluated in automotive development programs for important new applications. Thermoelectric materials are likely to become available that further increase performance by a comparable factor. These major advancements should allow the use of thermoelectric systems in new applications that have the prospect of contributing to emissions reduction, fuel economy, and improved user comfort. Potential applications of thermoelectrics in diesel vehicles are identified and discussed. As a case in point, the history and status of the Climate Controlled Seat (CCS) system from Amerigon, the parent of BSST, is presented. CCS is the most successful and highest production volume thermoelectric system in vehicles today. As a second example, the results of recent analyses on electric power generation from vehicle waste heat are discussed. Conclusions are drawn as to the practicality of waste power generation systems that incorporate BSST's thermodynamic cycle and advanced thermoelectric materials.

  20. Marine bioactives and potential application in sports.

    PubMed

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D'Orazio, Nicolantonio

    2014-04-30

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  1. Marine Bioactives and Potential Application in Sports

    PubMed Central

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D’Orazio, Nicolantonio

    2014-01-01

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports. PMID:24796298

  2. WISP1/CCN4: A Potential Target for Inhibiting Prostate Cancer Growth and Spread to Bone

    PubMed Central

    Sonn, Robert; Kilts, Tina M.; de Castro, Luis F.; Maeda, Azusa; Fisher, Larry W.; Robey, Pamela G.; Berendsen, Agnes D.; Li, Li; McCartney-Francis, Nancy; Brown, Aaron C.; Crawford, Nigel P. S.; Molinolo, Alfredo; Jain, Alka; Fedarko, Neal S.; Young, Marian F.

    2013-01-01

    Prostate cancer (PC) is a leading cause of death in men however the factors that regulate its progression and eventual metastasis to bone remain unclear. Here we show that WISP1/CCN4 expression in prostate cancer tissues was up-regulated in early stages of the disease and, further, that it correlated with increased circulating levels of WISP1 in the sera of patients at early stages of the disease. WISP1 was also elevated in the mouse prostate cancer model TRAMP in the hypoplastic diseased tissue that develops prior to advanced carcinoma formation. When the ability of anti-WISP1 antibodies to reduce the spread of PC3-Luc cells to distant sites was tested it showed that twice weekly injections of anti-WISP1 antibodies reduced the number and overall size of distant tumors developed after intracardiac (IC) injection of PC3-Luc cells in mice. The ability of antibodies against WISP1 to inhibit growth of PC3-Luc cancer cells in mice was also evaluated and showed that twice weekly injections of anti-WISP1 antibodies reduced local tumor growth when examined in xenografts. To better understand the mechanism of action, the migration of PC3-Luc cells through membranes with or without a Matrigel™ barrier showed the cells were attracted to WISP1, and that this attraction was inhibited by treatment with anti-WISP1 antibodies. We also show the expression of WISP1 at the bone-tumor interface and in the stroma of early grade cancers suggested WISP1 expression is well placed to play roles in both fostering growth of the cancer and its spread to bone. In summary, the up-regulation of WISP1 in the early stages of cancer development coupled with its ability to inhibit spread and growth of prostate cancer cells makes it both a potential target and an accessible diagnostic marker for prostate cancer. PMID:23977121

  3. Transdermal testosterone application: pharmacokinetics and effects on pubertal status, short-term growth, and bone turnover.

    PubMed

    Mayo, A; Macintyre, H; Wallace, A M; Ahmed, S F

    2004-02-01

    The aim of the study was to assess the effect of transdermal testosterone on free testosterone concentrations in saliva and on short-term growth and bone turnover in boys with growth or pubertal delay. A prospective, randomized, crossover study was conducted over 26 wk with 4 wk of run-in, 8 wk of treatment I (8 or 12 h), 4 wk of washout, 8 wk of treatment II (8 or 12 h), and 4 wk of final washout. The main outcome measures were salivary testosterone profiles during the different study periods; weekly change in lower leg length (LLL) as measured by knemometry, i.e. LLL velocity; absolute and percentage change in bone alkaline phosphatase (bALP) levels; and deoxypyridinoline cross-links measured in urine. Eight boys who took part in the study had a median age of 13.5 yr (range, 12.4-14.9 yr), testicular volume of 3 ml (range, 2-6 ml), height SD score of -2.4 (range, -1.44 to -3.35), and bone age delay of 2 yr (range, 1-3.2 yr). Median salivary testosterone during 8- and 12-h treatments [179 pg/ml (range, 7-3579 pg/ml) and 150 pg/ml (range, 12-3472 pg/ml) (not significant)] was significantly higher than during the run-in and washout blocks (P < 0.0001) [9 pg/ml (range, <7 to 122 pg/ml) and 13 pg/ml (range, <7 to 285 pg/ml) (not significant)]. LLL velocity in the treatment blocks (median, 0.64 mm/wk; range, 0.1-1.08 mm/wk) was significantly higher than during the run-in and washout periods (median, 0.48 mm/wk; range, -0.06 to 0.92 mm/wk) (P < 0.001). The main rise in bALP occurred during the first treatment block with a median percentage change in bALP of 44.2% (range, -4 to 87%) and a smaller percentage change in bALP at the end of the second treatment block of 9.8% (range, -4 to 55%). The increases in bALP were not significantly different between the 8- and 12-h treatment periods, and there was no significant decline during the washout periods. Overnight transdermal testosterone application, as Virormone (5 mg), may be a potentially acceptable method of induction of

  4. Curative potential of foremost mitogen applications.

    PubMed

    Wimer, Bruce M

    2003-12-01

    This paper is presented as a sequel to the Mitogen Information Summaries article, representing a condensation of salient features involved with facilitating the curative potential of the more important mitogen applications. Following is a resumé of the critical attributes of mitogen therapy relative to the management of malignant tumors: (1) An inherent capability to recognize and destroy mutated or damaged tissues without altering those that are normal; (2) The capacity to induce global immunostimulation by the nonspecific activation of CD4+/- and CD8+/- cells with balanced production of a variety of cytokines able to stimulate B cell, NK cell, and macrophage pathways, at the same time augmenting myeloproliferation; (3) The ability to afford protection and accelerated recovery from the immunosuppressive and myelosuppressive effects of tumors, infections, GvH reactions, and autoimmune states along with the surgery, irradiation, chemotherapeutic agents, antibiotics, and suppressive factors used in their management; (4) Berke's in vitro data from the lectin-dependent cellular cytotoxicity (LDCC) system showing that systemic administration of mitogens such as PHA-L4 should indeed prove destructive to virtually any type of malignancy, leaving normal tissues undamaged; and (5) The potential of these activities to reconstitute the immune competence so vital to lasting cures. The potential role of L4 immunotherapy for infections may be defined by the following criteria: those, including drug-resistant infections, not satisfactorily treatable otherwise; those in which a rapid response is essential; those that are subclinical, latent, recurrent, chronic, persistent, highly lethal, or opportunistic; those in patients with impaired immune responses; and most importantly, those that are not likely to be adversely affected by immunostimulation. Certain paths of administration such as the intralesional (for granulomas), intrapleural (for pleurisy, empyema), and intraperitoneal

  5. Epigenetic Pathways Regulating Bone Homeostasis: Potential Targeting for Intervention of Skeletal Disorders

    PubMed Central

    Gordon, Jonathan A. R.; Montecino, Martin A.; Aqeilan, Rami I.; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.

    2014-01-01

    Epigenetic regulation utilizes different mechanisms to convey heritable traits to progeny cells that are independent of DNA sequence, including DNA silencing, post-translational modifications of histone proteins and the post-transcriptional modulation of RNA transcript levels by non-coding RNAs. Although long non-coding RNAs have recently emerged as important regulators of gene imprinting, but their functions during osteogenesis are as yet unexplored. In contrast, microRNAs (miRNAs) are well characterized for their control of osteogenic and osteoclastic pathways; thus, further defining how gene regulatory networks essential for skeleton functions are coordinated and finely tuned through the activities of miRNAs. Roles of miRNAs are constantly expanding as new studies uncover associations with skeletal disorders. The distinct functions of epigenetic regulators and evidence for integrating their activities to control normal bone gene expression and bone disease will be presented. In addition, potential for using “signature microRNAs” to identify, manage and therapeutically treat osteosarcoma will be discussed in this review. PMID:25260661

  6. Epigenetic pathways regulating bone homeostasis: potential targeting for intervention of skeletal disorders.

    PubMed

    Gordon, Jonathan A R; Montecino, Martin A; Aqeilan, Rami I; Stein, Janet L; Stein, Gary S; Lian, Jane B

    2014-12-01

    Epigenetic regulation utilizes different mechanisms to convey heritable traits to progeny cells that are independent of DNA sequence, including DNA silencing, post-translational modifications of histone proteins, and the post-transcriptional modulation of RNA transcript levels by non-coding RNAs. Although long non-coding RNAs have recently emerged as important regulators of gene imprinting, their functions during osteogenesis are as yet unexplored. In contrast, microRNAs (miRNAs) are well characterized for their control of osteogenic and osteoclastic pathways; thus, further defining how gene regulatory networks essential for skeleton functions are coordinated and finely tuned through the activities of miRNAs. Roles of miRNAs are constantly expanding as new studies uncover associations with skeletal disorders. The distinct functions of epigenetic regulators and evidence for integrating their activities to control normal bone gene expression and bone disease will be presented. In addition, potential for using "signature miRNAs" to identify, manage, and therapeutically treat osteosarcoma will be discussed in this review.

  7. Preparation of collagen/hydroxyapatite/alendronate hybrid hydrogels as potential scaffolds for bone regeneration.

    PubMed

    Ma, Xin; He, Zhiwei; Han, Fengxuan; Zhong, Zhiyuan; Chen, Liang; Li, Bin

    2016-07-01

    Development of biomimetic scaffolds represents a promising direction in bone tissue engineering. In this study, we designed a two-step process to prepare a type of biomimetic hybrid hydrogels that were composed of collagen, hydroxyapatite (HAP) and alendronate (ALN), an anti-osteoporosis drug. First, water-soluble ALN-conjugated HAP (HAP-ALN) containing 4.0wt.% of ALN was synthesized by treating HAP particles with ALN. Hydrogels were then formed from HAP-ALN conjugate and collagen under physiological conditions using genipin (GNP) as the crosslinker. Depending on the ALN/collagen molar ratio and GNP concentration, the gelation time of hydrogels ranged from 5 to 37min. Notably, these hybrid hydrogels exhibited markedly improved mechanical property (storage modulus G'=38-187kPa), higher gel contents, and lower swelling ratios compared to the hydrogels prepared from collagen alone under similar conditions. Moreover, they showed tunable degradation behaviors against collagenase. The collagen/HAP-ALN hybrid hydrogels supported the adhesion and growth of murine MC3T3-E1 osteoblastic cells well. Such tough yet enzymatically degradable hybrid hydrogels hold potential as scaffolds for bone tissue engineering.

  8. Saccular function in otosclerosis patients: bone conducted-vestibular evoked myogenic potential analysis.

    PubMed

    Amali, Amin; Mahdi, Parvane; Karimi Yazdi, Alireza; Khorsandi Ashtiyani, Mohammad Taghi; Yazdani, Nasrin; Vakili, Varasteh; Pourbakht, Akram

    2014-01-01

    Vestibular involvements have long been observed in otosclerotic patients. Among vestibular structures saccule has the closest anatomical proximity to the sclerotic foci, so it is the most prone vestibular structure to be affected during the otosclerosis process. The aim of this study was to investigate the saccular function in patients suffering from otosclerosis, by means of Vestibular Evoked Myogenic Potential (VEMP). The material consisted of 30 otosclerosis patients and 20 control subjects. All participants underwent audiometric and VEMP testing. Analysis of tests results revealed that the mean values of Air-Conducted Pure Tone Average (AC-PTA) and Bone-Conducted Pure Tone Average (BC-PTA) in patients were 45.28 ± 15.57 and 19.68 ± 10.91, respectively and calculated 4 frequencies Air Bone Gap (ABG) was 25.64 ± 9.95. The VEMP response was absent in 14 (28.57%) otosclerotic ears. A statistically significant increase in latency of the p13 was found in the affected ears (P=0.004), differences in n23 latency did not reach a statistically significant level (P=0.112). Disparities in amplitude of p13-n23 in between two study groups was statistically meaningful (P=0.009), indicating that the patients with otosclerosis had lower amplitudes. This study tends to suggest that due to the direct biotoxic effect of the materials released from the otosclerosis foci on saccular receptors, there might be a possibility of vestibular dysfunction in otosclerotic patients.

  9. A facile magnesium-containing calcium carbonate biomaterial as potential bone graft.

    PubMed

    He, Fupo; Zhang, Jing; Tian, Xiumei; Wu, Shanghua; Chen, Xiaoming

    2015-12-01

    The calcium carbonate is the main composition of coral which has been widely used as bone graft in clinic. Herein, we readily prepared novel magnesium-containing calcium carbonate biomaterials (MCCs) under the low-temperature conditions based on the dissolution-recrystallization reaction between unstable amorphous calcium carbonate (ACC) and metastable vaterite-type calcium carbonate with water involved. The content of magnesium in MCCs was tailored by adjusting the proportion of ACC starting material that was prepared using magnesium as stabilizer. The phase composition of MCCs with various amounts of magnesium was composed of one, two or three kinds of calcium carbonates (calcite, aragonite, and/or magnesian calcite). The different MCCs differed in topography. The in vitro degradation of MCCs accelerated with increasing amount of introduced magnesium. The MCCs with a certain amount of magnesium not only acquired higher compressive strength, but also promoted in vitro cell proliferation and osteogenic differentiation. Taken together, the facile MCCs shed light on their potential as bone graft.

  10. Study of photoacoustic measurement of bone health based on clinically relevant models

    NASA Astrophysics Data System (ADS)

    Feng, Ting; Kozloff, Ken; Cao, Meng; Cheng, Qian; Yuan, Jie; Wang, Xueding

    2016-02-01

    Photoacoustic (PA) technique involving both ultrasound and light has been explored for potential application in the assessment of bone health. The optical and ultrasound penetration in bone have been studied. The feasibility of conducting 3D PA imaging of bone, and performing quantitative evaluation of bone microstructures by using photoacoustic spectrum analysis (PASA) has also been investigated. The findings from the experiments demonstrate that PA measurement could offer information of bone mineral density and bone microstructure, both relevant to bone health.

  11. Microfluidic desalination techniques and their potential applications.

    PubMed

    Roelofs, S H; van den Berg, A; Odijk, M

    2015-09-07

    In this review we discuss recent developments in the emerging research field of miniaturized desalination. Traditionally desalination is performed to convert salt water into potable water and research is focused on improving performance of large-scale desalination plants. Microfluidic desalination offers several new opportunities in comparison to macro-scale desalination, such as providing a platform to increase fundamental knowledge of ion transport on the nano- and microfluidic scale and new microfluidic sample preparation methods. This approach has also lead to the development of new desalination techniques, based on micro/nanofluidic ion-transport phenomena, which are potential candidates for up-scaling to (portable) drinking water devices. This review assesses microfluidic desalination techniques on their applications and is meant to contribute to further implementation of microfluidic desalination techniques in the lab-on-chip community.

  12. Engineering interaction between bone marrow derived endothelial cells and electrospun surfaces for artificial vascular graft applications.

    PubMed

    Ahmed, Furqan; Dutta, Naba K; Zannettino, Andrew; Vandyke, Kate; Choudhury, Namita Roy

    2014-04-14

    The aim of this investigation was to understand and engineer the interactions between endothelial cells and the electrospun (ES) polyvinylidene fluoride-co-hexafluoropropylene (PVDF-HFP) nanofiber surfaces and evaluate their potential for endothelialization. Elastomeric PVDF-HFP samples were electrospun to evaluate their potential use as small diameter artificial vascular graft scaffold (SDAVG) and compared with solvent cast (SC) PVDF-HFP films. We examined the consequences of fibrinogen adsorption onto the ES and SC samples for endothelialisation. Bone marrow derived endothelial cells (BMEC) of human origin were incubated with the test and control samples and their attachment, proliferation, and viability were examined. The nature of interaction of fibrinogen with SC and ES samples was investigated in detail using ELISA, XPS, and FTIR techniques. The pristine SC and ES PVDF-HFP samples displayed hydrophobic and ultrahydrophobic behavior and accordingly, exhibited minimal BMEC growth. Fibrinogen adsorbed SC samples did not significantly enhance endothelial cell binding or proliferation. In contrast, the fibrinogen adsorbed electrospun surfaces showed a clear ability to modulate endothelial cell behavior. This system also represents an ideal model system that enables us to understand the natural interaction between cells and their extracellular environment. The research reported shows potential of ES surfaces for artificial vascular graft applications.

  13. Application of labeling techniques to archival temporal bone sections.

    PubMed

    Tian, Q; Linthicum, F H; Keithley, E M

    1999-01-01

    Pathology of the human inner ear has traditionally been studied in celloidin-embedded, hematoxylin and eosin-stained sections of the temporal bone. Although the traditional histologic approach has yielded valuable information, it is now possible to extend these studies to include analysis of molecules using immunohistochemical and histochemical staining techniques. Fourteen antibodies and 6 lectins have been applied to 420 archival, celloidin-embedded human temporal bone sections. Tissues had been fixed in 10% formalin, embedded in celloidin, sectioned, and stored for as many as 40 years. The staining intensities varied among sections, so they were ranked from 'no label" to "dense label." To investigate the relationships between the extent of postmortem changes (PMCs), storage time, and staining intensity for each antibody, the sections were graded according to their PMCs, which ranged from good preservation of the temporal bone histologic structure to severe postmortem autolysis. Although statistical analysis indicated that both extent of PMCs and storage time in general decrease the staining intensity, both poorly fixed tissue and sections stored for a long time can yield good immunostaining results with some antibodies.

  14. Instrumentation for Investigating the Regenerative Potential of Bone-Tissue-Engineered Scaffolds

    DTIC Science & Technology

    2015-05-12

    hypothesized that PCL/HA and PLGA/HA scaffolds will mimic the nano -features of the natural extracellular matrix (ECM) and are expected to be effective...With the continual aging of the population in the United States, bone fractures and diseases such as osteoporosis, osteomalacia and osteitis deformans...Paget’s disease of bone) present a need for the development and perfection of bone regeneration methods [1]. While numerous bone fractures can be

  15. Improving Recovery from Catastrophic Bone Injuries: An Animal Model for Assessing the Bone Reparative Potential of Progenitor Cell Therapy

    DTIC Science & Technology

    2009-08-01

    Col3.6 population (the largest in number) that contain osterix and AP but only very low levels of BSP or other osteogenic markers. However as the 6... osterix -GFP reporter to this two color combination to further refine the osteogenic progenitor population. d. Different tissue sources of progenitor cell...microarray of the SMAA/Col3.6 population does not express osterix or AP. Figure 3: The temporal formations and subsequent loss of bone in the calvarial

  16. Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells

    SciTech Connect

    Montesano, Roberto Sarkoezi, Rita; Schramek, Herbert

    2008-09-12

    Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hitherto unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.

  17. Raloxifene: Mechanism of Action, Effects on Bone Tissue, and Applicability in Clinical Traumatology Practice

    PubMed Central

    Rey, Jose R. Caeiro; Cervino, Eduardo Vaquero; Rentero, Maria Luz; Crespo, Emilio Calvo; Álvaro, Angel Oteo; Casillas, Marta

    2009-01-01

    Raloxifene, a member of the class of selective estrogen receptor modulators (SERM), reproduces the beneficial effects of estrogens on the skeletal systems, without the negative effects estrogens on breast and endometrium. This is a review article summarizing its mechanism, effects on bone and its applicability in traumatology clinical practice. In postmenopausal osteoporosis, this drug has been proven to decrease accelerated bone turnover, increase bone mineral density (BMD), and to structurally recover bone, decreasing the risk of vertebral fractures and the risk of non-vertebral fractures in patients with previous, severe vertebral fractures. Moreover, raloxifene appears to lower the risk of invasive breast cancer. Raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis. We can therefore conclude that raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis, while reducing the risk of breast cancer when used at the indicated dose of 60 mg/day and with a low incidence of side effects. PMID:19516920

  18. Matrix-mediated retention of osteogenic differentiation potential by human adult bone marrow stromal cells during ex vivo expansion.

    PubMed

    Mauney, Joshua R; Kaplan, David L; Volloch, Vladimir

    2004-07-01

    During prolonged cultivation ex vivo, adult bone marrow stromal stem cells (BMSCs) undergo two probably interdependent processes, replicative aging and a decline in differentiation potential. Recently, our results with primary human fibroblasts indicated that growth on denatured collagen (DC) matrix results in the reduction of the rate of cellular aging. The present study has been undertaken to test whether the growth of human BMSCs under the same conditions would translate into preservation of cellular aging-attenuated functions, such as the ability to express HSP70 in response to stress as well as of osteogenic differentiation potential. We report here that growth of BMSCs on a DC matrix versus tissue culture polystyrene significantly reduced one of the main manifestations of cellular aging, the attenuation of the ability to express a major protective stress response component, HSP70, increased the proliferation capacity of ex vivo expanded BMSCs, reduced the rate of morphological changes, and resulted in a dramatic increase in the retention of the potential to express osteogenic-specific functions and markers upon treatment with osteogenic stimulants. BMSCs are a promising and increasingly important cell source for tissue engineering as well as cell and gene therapeutic strategies. For use of BMSCs in these applications, ex vivo expansion is necessary to obtain a sufficient, therapeutically useful, number of cells; however, this results in the loss of differentiation potential. This problem is especially acute in older patients where more extensive in vitro expansion of smaller number of stem/progenitor cells is needed. The finding that growth on certain biomaterials preserves aging-attenuated functions, enhances proliferation capacity, and maintains differentiation potential of BMSCs indicates a promising approach to address this problem.

  19. Influence of irradiation on the osteoinductive potential of demineralized bone matrix.

    PubMed

    Wientroub, S; Reddi, A H

    1988-04-01

    Samples of demineralized bone matrix (DBM) were exposed to graduated doses of radiation (1-15 Megarad) (Mrad) utilizing a linear accelerator and then implanted into the thoracic region of Long-Evans rats. Subcutaneous implantation of DBM into allogenic rats induces endochondral bone. In response to matrix implantation, a cascade of events ensues; mesenchymal cell proliferation on day 3 postimplantation, chondrogenesis on day 7, calcification of the cartilagenous matrix and chondrolysis on day 9, and osteogenesis on day 11 resulting in formation of an ossicle containing active hemopoietic tissue. Bone formation was assessed by measuring alkaline phosphatase activity, the rate of mineralization was determined by measuring 45Ca incorporation to bone mineral, and 40Ca content measured the extent of mineralization; acid phosphatase activity was used as a parameter for bone resorption. The dose of radiation (2.5 Mrad) currently used by bone banks for sterilization of bone tissue did not destroy the bone induction properties of DBM. Furthermore, radiation of 3-5 Mrad even enhanced bone induction, insofar as it produced more bone at the same interval of time than was obtained from unirradiated control samples. None of the radiation doses used in these experiments abolished bone induction, although the response induced by matrix irradiated with doses higher than 5 Mrad was delayed.

  20. Photoacoustic imaging: a potential new platform for assessment of bone health

    NASA Astrophysics Data System (ADS)

    Feng, Ting; Kozloff, Kenneth M.; Hsiao, Yi-Sing; Xu, Guan; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

    2015-02-01

    The ultimate goal of this work is to develop a novel photoacoustic (QPA) platform for highly-sensitive and quantitative assessment of bone health. First, the feasibility to perform 3D photoacoustic imaging (PAI) of bone was investigated. Then another two techniques, including thermal photoacoustic measurement (TPAM) and photoacoustic spectral analysis (PASA), both being able to achieve quantitative results were investigated for bone characterization. TPAM, by evaluating the dependence of photoacoustic signal amplitude on the sample temperature, is sensitive to the chemical constituents in tissue and holds promise for assessment of bone mineral density (BMD). PASA characterizes micron size physical features in tissue, and has shown feasibility for objective assessment of bone microarchitecture (BMA). This integrated QPA platform can assess both bone mass and microstructure simultaneously without involving invasive biopsy or ionizing radiation. Since QPA is non-ionizing, non-invasive, and has sufficient penetration in both soft tissue and bone, it has unique advantages for clinical translation.

  1. Potential spermatogenesis recovery with bone marrow mesenchymal stem cells in an azoospermic rat model.

    PubMed

    Zhang, Deying; Liu, Xing; Peng, Jinpu; He, Dawei; Lin, Tao; Zhu, Jing; Li, Xuliang; Zhang, Yuanyuan; Wei, Guanghui

    2014-07-24

    Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit) were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy.

  2. Fibrin gel-immobilized primary osteoblasts in calcium phosphate bone cement: in vivo evaluation with regard to application as injectable biological bone substitute.

    PubMed

    Kneser, U; Voogd, A; Ohnolz, J; Buettner, O; Stangenberg, L; Zhang, Y H; Stark, G B; Schaefer, D J

    2005-01-01

    Osteogenic injectable bone substitutes may be useful for many applications. We developed a novel injectable bone substitute based on osteoblast-fibrin glue suspension and calcium phosphate bone cement (BC). Human osteoblasts were isolated from trabecular bone samples and cultured under standard conditions. Osteoblasts were suspended in fibrinogen solution (FS). BC was cured with thrombin solution. 8 x 4 mm injectable bone discs were prepared using silicon molds and a custom-made applicator device. Discs containing BC, BC/FS, or BC/FS/osteoblasts were implanted subcutaneously into athymic nude mice. After 3, 9 and 24 weeks, specimens were explanted and subjected to morphologic and biomechanical evaluation. In vitro fibrin gel-embedded osteoblasts displayed a differentiated phenotype as evidenced by alkaline phosphatase, collagen type 1 and von Kossa stains. A proportion of osteoblasts appeared morphologically intact over a 3-day in vitro period following application into the BC. BC/FS and BC/FS/osteoblast discs were sparsely infiltrated with vascularized connective tissue. There was no bone formation in implants from all groups. However, positive von Kossa staining only in BC/FS/osteoblast groups suggests engraftment of at least some of the transplanted cells. Biomechanical evaluation demonstrated initial stability of the composites. Young's modulus and maximal load did not differ significantly in the BC/FS and BC/FS/osteoblast groups. The practicability of osteoblast-containing injectable bone could be demonstrated. The dense microstructure and the suboptimal initial vascularization of the composites may explain the lack of bone formation. Modifications with regard to enhanced osteoblast survival are mandatory for a possible application as injectable osteogenic bone replacement system.

  3. Carbon Nanofiber/Polycaprolactone/Mineralized Hydroxyapatite Nanofibrous Scaffolds for Potential Orthopedic Applications.

    PubMed

    Elangomannan, Shinyjoy; Louis, Kavitha; Dharmaraj, Bhagya Mathi; Kandasamy, Venkata Saravanan; Soundarapandian, Kannan; Gopi, Dhanaraj

    2017-02-22

    Hydroxyapatite (Ca10 (PO4)6(OH)2, HAP), a multimineral substituted calcium phosphate is one of the most substantial bone mineral component that has been widely used as bone replacement materials because of its bioactive and biocompatible properties. However, the use of HAP as bone implants is restricted due to its brittle nature and poor mechanical properties. To overcome this defect and to generate suitable bone implant material, HAP is combined with biodegradable polymer (polycaprolactone, PCL). To enhance the mechanical property of the composite, carbon nanofibers (CNF) is incorporated to the composite, which has long been considered for hard and soft tissue implant due to its exceptional mechanical and structural properties. It is well-known that nanofibrous scaffold are the most-prominent material for the bone reconstruction. We have developed a new remarkable CNF/PCL/mineralized hydroxyapatite (M-HAP) nanofibrous scaffolds on titanium (Ti). The as-developed coatings were characterized by various techniques. The results indicate the formation and homogeneous distribution of components in the nanofibrous scaffolds. Incorporation of CNF into the PCL/M-HAP composite significantly improves the adhesion strength and elastic modulus of the scaffolds. Furthermore, the responses of human osteosarcoma (HOS MG63) cells cultured onto the scaffolds demonstrate that the viability of cells were considerably high for CNF-incorporated PCL/M-HAP than for PCL/M-HAP. In vivo analysis show the presence of soft fibrous tissue growth without any significant inflammatory signs, which suggests that incorporated CNF did not counteract the favorable biological roles of HAP. For load-bearing applications, research in various bone models is needed to substantiate the clinical availability. Thus, from the obtained results, we suggest that CNF/PCL/M-HAP nanofibrous scaffolds can be considered as potential candidates for orthopedic applications.

  4. Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: potential utility for adoptive immunotherapy.

    PubMed

    Liu, Bing; Ohishi, Kohshi; Orito, Yuki; Nakamori, Yoshiki; Nishikawa, Hiroyoshi; Ino, Kazuko; Suzuki, Kei; Matsumoto, Takeshi; Masuya, Masahiro; Hamada, Hirofumi; Mineno, Junichi; Ono, Ryoichi; Nosaka, Tetsuya; Shiku, Hiroshi; Katayama, Naoyuki

    2013-04-01

    T cell precursors are an attractive target for adoptive immunotherapy. We examined the regulation of human early T lymphopoiesis by human bone marrow stromal cells to explore in vitro manipulation of human T cell precursors in a human-only coculture system. The generation of CD7(+)CD56(-)cyCD3(-) proT cells from human hematopoietic progenitors on telomerized human bone marrow stromal cells was enhanced by stem cell factor, flt3 ligand, and thrombopoietin, but these stimulatory effects were suppressed by interleukin 3. Expression of Notch ligands Delta-1 and -4 on stromal cells additively promoted T cell differentiation into the CD7(+)cyCD3(+) pre-T cell stage, while cell growth was strongly inhibited. By combining these coculture systems, we found that initial coculture with telomerized stromal cells in the presence of stem cell factor, flt3 ligand, and thrombopoietin, followed by coculture on Delta-1- and -4-coexpressing stromal cells led to a higher percentage and number of pre-T cells. Adoptive immunotherapy using peripheral blood T cells transduced with a tumor antigen-specific T cell receptor (TCR) is a promising strategy but has several limitations, such as the risk of forming a chimeric TCR with the endogenous TCR. We demonstrated that incubation of TCR-transduced hematopoietic progenitors with the combination of coculture systems gave rise to CD7(+)TCR(+)CD3(+)CD1a(-) T cell precursors that rapidly proliferated and differentiated under the culture condition to induce mature T cell differentiation. These data show the regulatory mechanism of early T lymphopoiesis on human stromal cells and the potential utility of engineered human stromal cells to manipulate early T cell development for clinical application.

  5. TRPC6 regulates cell cycle progression by modulating membrane potential in bone marrow stromal cells

    PubMed Central

    Ichikawa, Jun; Inoue, Ryuji

    2014-01-01

    Background and Purpose Ca2+ influx is important for cell cycle progression, but the mechanisms involved seem to vary. We investigated the potential roles of transient receptor potential (TRP) channels and store-operated Ca2+ entry (SOCE)-related molecules STIM (stromal interaction molecule)/Orai in the cell cycle progression of rat bone marrow stromal cells (BMSCs), a reliable therapeutic resource for regenerative medicine. Experimental Approach PCR and immunoblot analyses were used to examine mRNA and protein levels, fluorescence imaging and patch clamping for Ca2+ influx and membrane potential measurements, and flow cytometry for cell cycle analysis. Key Results Cell cycle synchronization of BMSCs revealed S phase-specific enhancement of TRPC1, STIM and Orai mRNA and protein expression. In contrast, TRPC6 expression decreased in the S phase and increased in the G1 phase. Resting membrane potential (RMP) of BMSCs was most negative and positive in the S and G1 phases, respectively, and was accompanied by an enhancement and attenuation of SOCE respectively. Chemically depolarizing/hyperpolarizing the membrane erased these differences in SOCE magnitude during the cell cycle. siRNA knockdown of TRPC6 produced a negative shift in RMP, increased SOCE and caused redistribution of BMSCs with increased populations in the S and G2/M phases and accumulation of cyclins A2 and B1. A low concentration of Gd3+ (1 μM) suppressed BMSC proliferation at its concentration to inhibit SOC channels relatively specifically. Conclusions and Implications TRPC6, by changing the membrane potential, plays a pivotal role in controlling the SOCE magnitude, which is critical for cell cycle progression of BMSCs. This finding provides a new therapeutic strategy for regulating BMSC proliferation. PMID:25041367

  6. Polymer-ceramic nanocomposites for applications in the bone surgery

    NASA Astrophysics Data System (ADS)

    Stodolak, E.; Gadomska, K.; Lacz, A.; Bogun, M.

    2009-01-01

    The subject of this work was preparation and investigation of properties of a nanocomposite material based on polymer matrix modified with nanometric silica particles (SiO2). The composite matrix consisted of resorbable P(L/DL)LA polymer with certified biocompatibility. Nanometric silica was introduced into the matrix by means of ultrasonic homogenisation and/or mechanical stirring. The silica was introduced directly e.g. as nanoparticles or inside calcium alginate fibres which contained 3 wt.% of amorphous SiO2. Proper dispersion of nano-filliers was confirmed by means of thermal analysis (TG/DTA, DSC). It was observed, that the presence of inorganic nanoparticles influenced several surface parameters of the nanocomposites i.e. hydrophility (a decrease of surface energy) and topography (both in micro- and nano-scale). Additionally, the nanocomposites exhibited enhanced mechanical properties (Young's modulus, tensile strength) compared to the pure polymer. The nanocomposites were bioactive materials (SBF/3 days/37oC). Biological tests (MTT test) showed a good viability of human osteoblasts (hFOB 1.19) in contact with the nanocomposites surface. Results of preliminary biological tests carried out with the use of mother cells extracted from human bone marrow showed that the nanocomposites may provide differenation of bone cells.

  7. When size matters: differences in demineralized bone matrix particles affect collagen structure, mesenchymal stem cell behavior, and osteogenic potential.

    PubMed

    Dozza, B; Lesci, I G; Duchi, S; Della Bella, E; Martini, L; Salamanna, F; Falconi, M; Cinotti, S; Fini, M; Lucarelli, E; Donati, D

    2017-04-01

    Demineralized bone matrix (DBM) is a natural, collagen-based, osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM cytocompatibility and osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1-2 mm), medium (M, 0.5-1 mm), and small (S, <0.5 mm). After demineralization, the chemical-physical analysis clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. DBM-M displayed a preferable trend in almost all biological characteristics tested, although all DBM particles revealed an optimal cytocompatibility. Subcutaneous implantation of DBM particles into immunocompromised mice resulted in bone induction only for DBM-M. When sheep MSC were seeded onto particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. In conclusion, the collagen alteration in DBM-M is likely the best condition to promote bone induction in vivo. Furthermore, the choice of 0.5-1 mm particles may enable to obtain more efficient and consistent results among different research groups in bone tissue-engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1019-1033, 2017.

  8. PUF proteins: Cellular functions and potential applications.

    PubMed

    Kiani, Seyed Jalal; Taheri, Tahereh; Rafati, Sima; Samimi-Rad, Katayoun

    2016-09-14

    RNA-binding proteins play critical roles in the regulation of gene expression. Among several families of RNA-binding proteins, PUF (Pumilio and FBF) proteins have been the subject of extensive investigations, as they can bind RNA in a sequence-specific manner and they are evolutionarily conserved among a wide range of organisms. The outstanding feature of these proteins is a highly conserved RNA-binding domain, which is known as the Pumilio-homology domain (PUM-HD) that mostly consists of eight tandem repeats. Each repeat recognizes an RNA base with a simple three-letter code that can be programmed in order to change the sequence-specificity of the protein. Using this tailored architecture, researchers have been able to change the specificity of the PUM-HD and target desired transcripts in the cell, even in subcellular compartments. The potential applications of this versatile tool in molecular cell biology seem unbounded and the use of these factors in pharmaceutics might be an interesting field of study in near future.

  9. Vehicle bridge interaction dynamics and potential applications

    NASA Astrophysics Data System (ADS)

    Yang, Y. B.; Lin, C. W.

    2005-06-01

    The dynamic interaction between a moving vehicle and the sustaining bridge is studied. By the method of modal superposition, closed-form solutions are obtained for the vertical responses of both the bridge and moving vehicle, assuming the vehicle/bridge mass ratio to be small. For both the bridge and vehicle responses, it is confirmed that rather accurate solutions can be obtained by considering only the first mode. The displacement, velocity, and acceleration of the bridge are governed at different extents by two sets of frequencies, i.e., the driving frequency of the vehicle and natural frequencies of the bridge. From the spectrum for the bridge displacement, the vehicle speeds can be shown to be associated with some low-frequency pikes. On the other hand, the vehicle responses are governed by five distinct frequencies that appear as driving frequencies, vehicle frequency, and bridge frequencies with shift. From the vehicle's acceleration spectrum, the first bridge frequency (with shift) is shown to have rather high visibility and can be easily identified. The effects of damping of the vehicle and bridge are evaluated in the numerical studies. Potential applications of the present results, as well as further researches required, are also indicated in the paper.

  10. Potential applications of insect symbionts in biotechnology.

    PubMed

    Berasategui, Aileen; Shukla, Shantanu; Salem, Hassan; Kaltenpoth, Martin

    2016-02-01

    Symbiotic interactions between insects and microorganisms are widespread in nature and are often the source of ecological innovations. In addition to supplementing their host with essential nutrients, microbial symbionts can produce enzymes that help degrade their food source as well as small molecules that defend against pathogens, parasites, and predators. As such, the study of insect ecology and symbiosis represents an important source of chemical compounds and enzymes with potential biotechnological value. In addition, the knowledge on insect symbiosis can provide novel avenues for the control of agricultural pest insects and vectors of human diseases, through targeted manipulation of the symbionts or the host-symbiont associations. Here, we discuss different insect-microbe interactions that can be exploited for insect pest and human disease control, as well as in human medicine and industrial processes. Our aim is to raise awareness that insect symbionts can be interesting sources of biotechnological applications and that knowledge on insect ecology can guide targeted efforts to discover microorganisms of applied value.

  11. Application potential of rechargeable lithium batteries

    SciTech Connect

    Hunger, H.F.; Bramhall, P.J.

    1983-10-01

    Rechargeable lithium cells with Cr /SUB 0.5/ V/sub 0/ /sub 5/S/sub 2/ and MoO/sub 3/ cathodes were investigated in the temperature range of -30/sup 0/C to +25/sup 0/C. The electrolyte was 1.5M LiAsF/sub 6/ in 2-methyl tetrahydrofuran with tetrahydrofuran (50:50 V percent). Current densities and capacities as a function of temperature, cathode utilization efficiencies versus cycle life, and shelf lives were determined. The state of charge could be related to open circuit voltages after partial discharge. The potential of the system for communication applications is discussed. Recent advances in rechargeable lithium batteries were mainly due to the discovery of stable, cyclic ether electrolyte solvents (1) and to the use of rechargeable cathode materials (2). The practical usefulness of rechargeable lithium cells with Cr /SUB 0.5/ V /SUB 0.5/ S/sub 2/ and MoO/sub 3/ cathodes was investigated in the temperature range of -30/sup 0/C to +25/sup 0/C. The electrolyte was mainly 1.5M LiAsF/sub 6/ in 2-methyl tetrahydrofuran with tetrahydrofuran (50:50 V percent). The two cathode materials were chosen because Cr /SUB 0.5/ V /SUB 0.5/ S/sub 2/ resembles TiS/sub 2/ in capacity and cycling behavior and MoO/sub 3/ is a low cost cathode material of interest.

  12. New Potential Pharmaceutical Applications of Hypericum Species.

    PubMed

    Marrelli, Mariangela; Statti, Giancarlo; Conforti, Filomena; Menichini, Francesco

    2016-01-01

    The genus Hypericum includes more than 450 species distributed in Europe, North America, North Africa and West Asia. These plants are widely used in folk medicine for the treatment of inflammation, bacterial and viral infections, burns and gastric disorders. The use for alleviating inflammation and promoting wound healing is well known for H. Perforatum L. (St. John's wort) and other species. Because of its pharmacological activity, H. perforatum L. is one of the most important species of this genus. This plant has been largely utilized for its efficacy in the treatment of mild to moderate depression. However, some other species have been utilized in traditional medicine and have been studied for their phytochemical composition and for their biological activities to date. Hypericum species contain biologically active secondary metabolites belonging to at least ten different classes, with prevalence of naphthodianthrones (hypericin and pseudohypericin), phloroglucinols (hyperforin), flavonoids (rutin, hyperoside, isoquercitrin, quercitrin, quercetin, amentoflavone) and phenylpropanoids (chlorogenic acid). However, great variations in contents have been reported for wild populations worldwide. The purpose of this review is to provide an overview of most recent studies about potential pharmaceutical applications of plants belonging to Hypericum genus. The most interesting isolated active principles and both in vitro and in vivo effects of Hypericum extracts are presented and discussed.

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

    PubMed

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

    2016-03-01

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

  14. Therapeutic application of mesenchymal stem cells in bone and joint diseases.

    PubMed

    Liu, Yi; Wu, Jianmei; Zhu, Youming; Han, Jinxiang

    2014-02-01

    Mesenchymal stem cells (MSCs), the non-hematopoietic progenitor cells, are multi-potent stem cells from a variety of tissues with the capability of self-renewal, proliferation, differentiation into multi-lineage cell types, as well as anti-inflammatory and immunomodulatory. These properties make MSCs an ideal source of cell therapy in bone and joint diseases. This review describes the advances of animal study and preliminary clinical application in the past few years, related to MSC-based cell therapy in the common bone and joint diseases, including osteoarthritis, rheumatoid arthritis, osteoporosis, osteonecrosis of the femoral head and osteogenesis imperfecta. It highlights the promising prospect of MSC in clinical application of bone and joint diseases.

  15. High Potential for Using DNA from Ancient Herring Bones to Inform Modern Fisheries Management and Conservation

    PubMed Central

    Speller, Camilla F.; Hauser, Lorenz; Lepofsky, Dana; Moore, Jason; Rodrigues, Antonia T.; Moss, Madonna L.; McKechnie, Iain; Yang, Dongya Y.

    2012-01-01

    Pacific herring (Clupea pallasi) are an abundant and important component of the coastal ecosystems for the west coast of North America. Current Canadian federal herring management assumes five regional herring populations in British Columbia with a high degree of exchange between units, and few distinct local populations within them. Indigenous traditional knowledge and historic sources, however, suggest that locally adapted, distinct regional herring populations may have been more prevalent in the past. Within the last century, the combined effects of commercial fishing and other anthropogenic factors have resulted in severe declines of herring populations, with contemporary populations potentially reflecting only the remnants of a previously more abundant and genetically diverse metapopulation. Through the analysis of 85 archaeological herring bones, this study attempted to reconstruct the genetic diversity and population structure of ancient herring populations using three different marker systems (mitochondrial DNA (mtDNA), microsatellites and SNPs). A high success rate (91%) of DNA recovery was obtained from the extremely small herring bone samples (often <10 mg). The ancient herring mtDNA revealed high haplotype diversity comparable to modern populations, although population discrimination was not possible due to the limited power of the mtDNA marker. Ancient microsatellite diversity was also similar to modern samples, but the data quality was compromised by large allele drop-out and stuttering. In contrast, SNPs were found to have low error rates with no evidence for deviations from Hardy-Weinberg equilibrium, and simulations indicated high power to detect genetic differentiation if loci under selection are used. This study demonstrates that SNPs may be the most effective and feasible approach to survey genetic population structure in ancient remains, and further efforts should be made to screen for high differentiation markers.This study provides the much

  16. Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency.

    PubMed

    Russell, Katie C; Lacey, Michelle R; Gilliam, Jennifer K; Tucker, H Alan; Phinney, Donald G; O'Connor, Kim C

    2011-11-01

    Human mesenchymal stem cells (MSCs) from bone marrow are a heterogeneous ensemble of progenitors and lineage-committed cells, with a broad range of regenerative properties. Ex vivo expansion to produce sufficient quantities of MSCs is essential for most therapeutic applications. The present study resolves the relationship between proliferation potential of MSCs and their potency. Clonal analysis generated single-cell derived colonies of MSCs that were classified according to their trilineage potential to exhibit adipo- (A), chondro- (C), and osteogenesis (O) as a measure of potency. Multipotent OAC clones were highly proliferative with colony-forming efficiencies that ranged from 35% to 90%; whereas, O clones formed colonies with an efficiency of 5% or less (P < 0.01). Similar trends were evident during ex vivo expansion: for example, the median specific growth rate was 0.8  day(-1) (20 h doubling time) for cultures inoculated with OAC clones and was 5-fold less for inocula of O clones (P < 0.01). OA and OC clones had similar proliferation potentials. More than 75% of cells in subconfluent cultures inoculated with O clones stained positive for senescence-associated β-galactosidase activity vs. less than 10% for OAC clones (P < 0.001). Apoptotic cells were in the minority for all potency groups. Preliminary data generated during clonal analysis suggest that osteogenic potential of MSCs to produce mineralized matrix is a function of potency, as well. These results are discussed in the context of the preparation of efficacious MSC therapies by ex vivo expansion.

  17. Hydrogel/bioactive glass composites for bone regeneration applications: synthesis and characterisation.

    PubMed

    Killion, John A; Kehoe, Sharon; Geever, Luke M; Devine, Declan M; Sheehan, Eoin; Boyd, Daniel; Higginbotham, Clement L

    2013-10-01

    Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications.

  18. Application of Ultrasonic Bone Curette in Endoscopic Endonasal Skull Base Surgery: Technical Note

    PubMed Central

    Rastelli, Milton M.; Pinheiro-Neto, Carlos D.; Fernandez-Miranda, Juan C.; Wang, Eric W.; Snyderman, Carl H.; Gardner, Paul A.

    2014-01-01

    Background Endoscopic endonasal surgery (EES) of the skull base often requires extensive bone work in proximity to critical neurovascular structures. Objective To demonstrate the application of an ultrasonic bone curette during EES. Methods Ten patients with skull base lesions underwent EES from September 2011 to April 2012 at the University of Pittsburgh Medical Center. Most of the bone work was done with high-speed drill and rongeurs. The ultrasonic curette was used to remove specific structures. Results All the patients were submitted to fully endoscopic endonasal procedures and had critical bony structures removed with the ultrasonic bone curette. Two patients with degenerative spine diseases underwent odontoid process removal. Five patients with clival and petroclival tumors underwent posterior clinoid removal. Two patients with anterior fossa tumors underwent crista galli removal. One patient underwent unilateral optic nerve decompression. No mechanical or heat injury resulted from the ultrasonic curette. The surrounding neurovascular structures and soft tissue were preserved in all cases. Conclusion In selected EES, the ultrasonic bone curette was successfully used to remove loose pieces of bone in narrow corridors, adjacent to neurovascular structures, and it has advantages to high-speed drills in these specific situations. PMID:24719795

  19. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    PubMed

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities.

  20. Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats.

    PubMed

    Salem, Ahmed M; Ahmed, Hanaa H; Atta, Hazem M; Ghazy, Mohamed A; Aglan, Hadeer A

    2014-12-01

    Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly, there is an urgent need to develop novel and effective medications for AD. Stem cell-based therapy is a promising approach to handling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of single intravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains and produced significant increases in the number of positive cells for choline acetyltransferase (ChAT) and survivin expression, as well as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus. Significant improvement in these biomarkers was similar to or better sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory properties.

  1. Matrix-mediated retention of adipogenic differentiation potential by human adult bone marrow-derived mesenchymal stem cells during ex vivo expansion.

    PubMed

    Mauney, Joshua R; Volloch, Vladimir; Kaplan, David L

    2005-11-01

    Recently, cell-based approaches utilizing adipogenic progenitor cells for fat tissue engineering have been developed and reported to have success in promoting in vivo adipogenesis and the repair of defect sites. For autologous applications, human bone marrow-derived mesenchymal stem cells (MSCs) have been suggested as a potential cell source for adipose tissue engineering applications due to their ability to be isolated and ex vivo expanded from adult bone marrow aspirates and their versatility for pluripotent differentiation into various mesenchymal lineages including adipogenic. Due to the relatively low frequency of MSCs present within bone marrow, extensive ex vivo expansion of these cells is necessary to obtain therapeutic cell populations for tissue engineering strategies. Currently, utilization of MSCs for adipose tissue engineering is limited due to the attenuation of their adipogenic differentiation potential following extensive ex vivo expansion on conventional tissue culture plastic (TCP) substrates. In the present study, the ability of a denatured collagen type I (DC) matrix to preserve MSC adipogenic potential during ex vivo expansion was examined. Adipocyte-related markers and functions were examined in vitro in response to adipogenic culture conditions for 21 days in comparison to early passage MSCs and late passage MSCs ex vivo expanded on TCP. The results demonstrated significant preservation of the ability of late passage MSCs ex vivo expanded on the DC matrix to express adipogenic markers (fatty acid-binding protein-4, lipoprotein lipase, acyl-CoA synthetase, adipsin, facilitative glucose transporter-4, and accumulation of lipids) similar to the early passage cells and in contrast to late passage MSCs expanded on TCP. The ability of the DC matrix to preserve adipocyte-related markers and functions of MSCs following extensive ex vivo expansion represents a novel culture technique to expand functional adipogenic progenitors for tissue engineering

  2. [Evidences of physical agents action on bone metabolism and their potential clinical use].

    PubMed

    Lirani, Ana Paula R; Lazaretti-Castro, Marise

    2005-12-01

    The action of physical agents such as low level laser therapy, low-intensity pulsed ultrasound and electrical and electromagnetic fields on bone have been often studied, showing that they are able to promote osteogenesis, accelerate fracture consolidation and augment bone mass. The use of these therapeutic modalities was first based on the finding that bone is a piezoelectric material, that means it can generate polarization when deformed, transforming mechanical energy into electric energy, and this has widen therapeutic possibilities to bony tissue. The present work aims to present evidences of physiologic effects and mechanisms of action of these physical agents on bone metabolism, based on articles published in international scientific literature.

  3. Two applications of potential vorticity thinking

    NASA Technical Reports Server (NTRS)

    Robinson, Walter A.

    1987-01-01

    The phenomena of dissipative destabilization of external Rossby waves and the acceleration of the zonal mean jet during baroclinic life cycles are described in terms of potential vorticity. The main principle of the potential temperature variations at rigid boundaries have the same effect on the interior flow as do sheets of potential vorticity located just within the boundaries. It is noted that the potential vorticity theory is useful for understanding the dynamical behavior of meterological phenomena.

  4. Bone morphogenetic protein

    SciTech Connect

    Xiao Yongtao; Xiang Lixin; Shao Jianzhong

    2007-10-26

    Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor-beta superfamily. It has been demonstrated that BMPs had been involved in the regulation of cell proliferation, survival, differentiation and apoptosis. However, their hallmark ability is that play a pivotal role in inducing bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. In this review, we mainly concentrate on BMP structure, function, molecular signaling and potential medical application.

  5. Quantification of bone mass gain in response to the application of biphasic bioceramics and platelet concentrate in critical-size bone defects.

    PubMed

    Lobo, Sonja Ellen; Wykrota, Francisco Henrique Lanna; Oliveira, Ana Carolina Marques Barbosa; Kerkis, Irina; Mahecha, Germán Bohorquez; Alves, Humberto José

    2009-05-01

    Biphasic bioceramics have been widely indicated for bone reconstruction; however, the real gain in bone mass due to the presence of such biomaterials has not been established yet nor the advantages of its association with platelet concentrate. This study aims at quantifying the volume of bone matrix, osteoblasts, osteocytes, blood vessels and adipose tissue after the application of a biphasic bioceramics composed of 65% hydroxyapatite and 35% beta-tricalcium phosphate. Critical-size bone defects were produced in rabbit femora and reconstructed with bioceramics only, with bioceramics combined with platelet concentrate, with platelet concentrate alone, and with no treatment (blood clot). The quantitative evaluation was performed on histological sections using histomorphometry. Our data provide original evidence that consolidates the indication of bioceramics for clinical bone loss reconstruction. The application of biphasic bioceramics alone led to major bone mass gain and was followed by its association with platelet concentrate. On the other hand, platelet concentrate can contribute to the augmentation and maintenance of the adipose tissue, representing a new field for future applications in plastic surgery.

  6. The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

    PubMed Central

    Mezentseva, Nadejda V.; Yang, Jinpu; Kaur, Keerat; Iaffaldano, Grazia; Rémond, Mathieu C.; Eisenberg, Carol A.

    2013-01-01

    Bone marrow (BM) has long been considered a potential stem cell source for cardiac repair due to its abundance and accessibility. Although previous investigations have generated cardiomyocytes from BM, yields have been low, and far less than produced from ES or induced pluripotent stem cells (iPSCs). Since differentiation of pluripotent cells is difficult to control, we investigated whether BM cardiac competency could be enhanced without making cells pluripotent. From screens of various molecules that have been shown to assist iPSC production or maintain the ES cell phenotype, we identified the G9a histone methyltransferase inhibitor BIX01294 as a potential reprogramming agent for converting BM cells to a cardiac-competent phenotype. BM cells exposed to BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and islet1, which are genes associated with embryonic cardiac progenitors. In contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and pluripotency gene expression by BM cells. Expression of cardiac-associated genes Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114, 76, 276, 46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11 when BM cells were pretreated with BIX01294. Immunofluorescent analysis demonstrated that BIX01294 exposure allowed for the subsequent display of various muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype and differentiation potential corresponded to an overall decrease in methylation of histone H3 at lysine9, which is the primary target of G9a histone methyltransferase. In summary, these data suggest that BIX01294 inhibition of chromatin methylation reprograms BM cells to a cardiac-competent progenitor phenotype. PMID:22994322

  7. The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells.

    PubMed

    Mezentseva, Nadejda V; Yang, Jinpu; Kaur, Keerat; Iaffaldano, Grazia; Rémond, Mathieu C; Eisenberg, Carol A; Eisenberg, Leonard M

    2013-02-15

    Bone marrow (BM) has long been considered a potential stem cell source for cardiac repair due to its abundance and accessibility. Although previous investigations have generated cardiomyocytes from BM, yields have been low, and far less than produced from ES or induced pluripotent stem cells (iPSCs). Since differentiation of pluripotent cells is difficult to control, we investigated whether BM cardiac competency could be enhanced without making cells pluripotent. From screens of various molecules that have been shown to assist iPSC production or maintain the ES cell phenotype, we identified the G9a histone methyltransferase inhibitor BIX01294 as a potential reprogramming agent for converting BM cells to a cardiac-competent phenotype. BM cells exposed to BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and islet1, which are genes associated with embryonic cardiac progenitors. In contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and pluripotency gene expression by BM cells. Expression of cardiac-associated genes Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114, 76, 276, 46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11 when BM cells were pretreated with BIX01294. Immunofluorescent analysis demonstrated that BIX01294 exposure allowed for the subsequent display of various muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype and differentiation potential corresponded to an overall decrease in methylation of histone H3 at lysine9, which is the primary target of G9a histone methyltransferase. In summary, these data suggest that BIX01294 inhibition of chromatin methylation reprograms BM cells to a cardiac-competent progenitor phenotype.

  8. Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model

    PubMed Central

    Zhang, Deying; Liu, Xing; Peng, Jinpu; He, Dawei; Lin, Tao; Zhu, Jing; Li, Xuliang; Zhang, Yuanyuan; Wei, Guanghui

    2014-01-01

    Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit) were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy. PMID:25062349

  9. Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

    PubMed Central

    Chen, Chider; Xu, Xingtian; Akiyama, Kentaro; Ansari, Sahar; Zadeh, Homayoun H.; Shi, Songtao

    2014-01-01

    Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD- (arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications. PMID:24070211

  10. Magnetic Nanocomposite Hydrogel for Potential Cartilage Tissue Engineering: Synthesis, Characterization, and Cytocompatibility with Bone Marrow Derived Mesenchymal Stem Cells.

    PubMed

    Zhang, Naiyin; Lock, Jaclyn; Sallee, Amy; Liu, Huinan

    2015-09-23

    Hydrogels possess high water content and closely mimic the microenvironment of extracellular matrix. In this study, we created a hybrid hydrogel containing type II collagen, hyaluronic acid (HA), and polyethylene glycol (PEG) and incorporated magnetic nanoparticles into the hybrid hydrogels of type II collagen-HA-PEG to produce a magnetic nanocomposite hydrogel (MagGel) for cartilage tissue engineering. The results showed that both the MagGel and hybrid gel (Gel) were successfully cross-linked and the MagGel responded to an external magnet while maintaining structural integrity. That is, the MagGel could travel to the tissue defect sites in physiological fluids under remote magnetic guidance. The adhesion density of bone marrow derived mesenchymal stem cells (BMSCs) on the MagGel group in vitro was similar to the control group and greater than the Gel group. The morphology of BMSCs was normal and consistent in all groups. We also found that BMSCs engulfed magnetic nanoparticles in culture and the presence of magnetic nanoparticles did not affect BMSC adhesion and morphology. We hypothesized that the ingested nanoparticles may be eventually broken down by lysosome and excreted through exocytosis; further studies are necessary to confirm this. This study reports a promising magnetic responsive nanocomposite hydrogel for potential cartilage tissue engineering applications, which should be further studied for its effects on cell functions when combined with electromagnetic stimulation.

  11. Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells

    SciTech Connect

    Tu Qisheng; Valverde, Paloma . E-mail: paloma.valverde@tufts.edu; Chen, Jake

    2006-03-24

    Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null mice osteoblast differentiation is impaired and bone formation is absent. In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non-differentiating medium did not affect expression of Runx2/Cbfa1, another key transcription factor of osteoblast differentiation, but induced an increase in the expression of other markers associated with the osteoblastic lineage including alkaline phosphatase, bone sialoprotein, osteocalcin, and osteopontin. Retroviral transduction of Osx in BMSC also increased their proliferation, alkaline phosphatase activity, and ability to form bone nodules. These events occurred without significant changes in the expression of {alpha}1(II) procollagen or lipoprotein lipase, which are markers of chondrogenic and adipogenic differentiation, respectively.

  12. Automated cortical bone segmentation for multirow-detector CT imaging with validation and application to human studies

    PubMed Central

    Li, Cheng; Jin, Dakai; Chen, Cheng; Letuchy, Elena M.; Janz, Kathleen F.; Burns, Trudy L.; Torner, James C; Levy, Steven M.; Saha, Punam K

    2015-01-01

    Purpose: Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow-detector CT (MD-CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal-to-noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD-CT imaging is presented and its performance and application are examined. Methods: The algorithm is completed in two major steps—(1) bone filling, alignment, and region-of-interest computation and (2) segmentation of cortical bone. After the first step, the following sequence of tasks is performed to accomplish cortical bone segmentation—(1) detection of marrow space and possible pores, (2) computation of cortical bone thickness, detection of recession points, and confirmation and filling of true pores, and (3) detection of endosteal boundary and delineation of cortical bone. Effective generalizations of several digital topologic and geometric techniques are introduced and a fully automated algorithm is presented for cortical bone segmentation. Results: An accuracy of 95.1% in terms of volume of agreement with manual outlining of cortical bone was observed in human MD-CT scans, while an accuracy of 88.5% was achieved when compared with manual outlining on postregistered high resolution micro-CT imaging. An intraclass correlation coefficient of 0.98 was obtained in cadaveric repeat scans. A pilot study was conducted to describe gender differences in cortical bone properties. This study involved 51 female and 46 male participants (age: 19–20 yr) from the Iowa Bone Development Study. Results from this pilot study suggest that, on average after adjustment for height

  13. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    SciTech Connect

    Saha, Sushmita; Kirkham, Jennifer; Wood, David; Curran, Stephen; Yang, Xuebin

    2010-10-22

    Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed

  14. Tea and bone health: Findings from human studies, potential mechanisms, and identification of knowledge gaps.

    PubMed

    Nash, Leslie A; Ward, Wendy E

    2017-05-24

    The population of the developed world is aging. With this aging population, strategies for prevention rather than treatment of chronic disease, such as osteoporosis, are essential for preserving quality of life and reducing health care costs. Tea is the second most consumed beverage in the world and is a rich source of flavonoids that may benefit bone health. There is strong evidence from human studies that habitual tea consumption is positively associated with higher BMD at multiple skeletal sites, while the association with fracture risk is less clear. Fracture studies demonstrate a reduction or no difference in fragility fracture with tea consumption. There are key questions that need to be answered in future studies to clarify if higher consumption of tea not only supports a healthy BMD, but also reduces the risk of fragility fracture. And if the latter relationship is shown to exist, studies to elucidate mechanisms can be designed and executed. This review discusses findings from epidemiological studies as well as potential mechanisms by which flavonoids in tea may mediate an effect, and identifies key knowledge gaps in this research area.

  15. Influence of age on rat bone-marrow mesenchymal stem cells potential.

    PubMed

    Fafián-Labora, J; Fernández-Pernas, P; Fuentes, I; De Toro, J; Oreiro, N; Sangiao-Alvarellos, S; Mateos, J; Arufe, M C

    2015-11-19

    Mesenchymal stem cells promising role in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age. Six age groups from bone marrow mesenchymal stem cells of Wistar rats were studied (newborn, infant, young, pre-pubertal, pubertal and adult). Quantitative proteomic assay was performance by iTRAQ using an 8-plex iTRAQ labeling and the proteins differentially expressed were grouped in pluripotency, proliferative and metabolism processes. Proliferation makers, CD117 and Ki67 were measure by flow cytometry assay. Real time polymerase chain reaction analysis of pluripotency markers Rex1, Oct4, Sox2 and Nanog were done. Biological differentiation was realized using specific mediums for 14 days to induce osteogenesis, adipogenesis or chondrogenesis and immunostain analysis of differentiated cell resulting were done. Enzimoimmunoassay analysis of several enzymes as L-lactate dehydrogenase and glucose-6-phosphate isomerase were also done to validate iTRAQ data. Taking together these results indicate for the first time that mesenchymal stem cells have significant differences in their proliferative, pluripotency and metabolism profiles and those differences are age depending.

  16. Bone-Targeted Acid-Sensitive Doxorubicin Conjugate Micelles as Potential Osteosarcoma Therapeutics

    PubMed Central

    2015-01-01

    Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic d-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data. PMID:25291150

  17. Influence of age on rat bone-marrow mesenchymal stem cells potential

    PubMed Central

    Fafián-Labora, J.; Fernández-Pernas, P.; Fuentes, I.; De Toro, J.; Oreiro, N.; Sangiao-Alvarellos, S.; Mateos, J.; Arufe, M.C.

    2015-01-01

    Mesenchymal stem cells promising role in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age. Six age groups from bone marrow mesenchymal stem cells of Wistar rats were studied (newborn, infant, young, pre-pubertal, pubertal and adult). Quantitative proteomic assay was performance by iTRAQ using an 8-plex iTRAQ labeling and the proteins differentially expressed were grouped in pluripotency, proliferative and metabolism processes. Proliferation makers, CD117 and Ki67 were measure by flow cytometry assay. Real time polymerase chain reaction analysis of pluripotency markers Rex1, Oct4, Sox2 and Nanog were done. Biological differentiation was realized using specific mediums for 14 days to induce osteogenesis, adipogenesis or chondrogenesis and immunostain analysis of differentiated cell resulting were done. Enzimoimmunoassay analysis of several enzymes as L-lactate dehydrogenase and glucose-6-phosphate isomerase were also done to validate iTRAQ data. Taking together these results indicate for the first time that mesenchymal stem cells have significant differences in their proliferative, pluripotency and metabolism profiles and those differences are age depending. PMID:26581954

  18. Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics.

    PubMed

    Low, Stewart A; Yang, Jiyuan; Kopeček, Jindřich

    2014-11-19

    Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic D-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data.

  19. Morphological features of the macerated cranial bones registered by the 3D vision system for potential use in forensic anthropology.

    PubMed

    Skrzat, Janusz; Sioma, Andrzej; Kozerska, Magdalena

    2013-01-01

    In this paper we present potential usage of the 3D vision system for registering features of the macerated cranial bones. Applied 3D vision system collects height profiles of the object surface and from that data builds a three-dimensional image of the surface. This method appeared to be accurate enough to capture anatomical details of the macerated bones. With the aid of the 3D vision system we generated images of the surface of the human calvaria which was used for testing the system. Performed reconstruction visualized the imprints of the dural vascular system, cranial sutures, and the three-layer structure of the cranial bones observed in the cross-section. We figure out that the 3D vision system may deliver data which can enhance estimation of sex from the osteological material.

  20. Fabrication, pore structure and compressive behavior of anisotropic porous titanium for human trabecular bone implant applications.

    PubMed

    Li, Fuping; Li, Jinshan; Xu, Guangsheng; Liu, Gejun; Kou, Hongchao; Zhou, Lian

    2015-06-01

    Porous titanium with average pore size of 100-650 μm and porosity of 30-70% was fabricated by diffusion bonding of titanium meshes. Pore structure was characterized by Micro-CT scan and SEM. Compressive behavior of porous titanium in the out-of-plane direction was studied. The effect of porosity and pore size on the compressive properties was also discussed based on the deformation mode. The results reveal that the fabrication process can control the porosity precisely. The average pore size of porous titanium can be tailored by adjusting the pore size of titanium meshes. The fabricated porous titanium possesses an anisotropic structure with square pores in the in-plane direction and elongated pores in the out-of-plane direction. The compressive Young's modulus and yield stress are in the range of 1-7.5 GPa and 10-110 MPa, respectively. The dominant compressive deformation mode is buckling of mesh wires, but some uncoordinated buckling is present in porous titanium with lower porosity. Relationship between compressive properties and porosity conforms well to the Gibson-Ashby model. The effect of pore size on compressive properties is fundamentally ascribed to the aspect ratio of titanium meshes. Porous titanium with 60-70% porosity has potential for trabecular bone implant applications.

  1. Nanohydroxyapatite incorporated electrospun polycaprolactone/polycaprolactone-polyethyleneglycol-polycaprolactone blend scaffold for bone tissue engineering applications.

    PubMed

    Remya, K R; Joseph, Jasmin; Mani, Susan; John, Annie; Varma, H K; Ramesh, P

    2013-09-01

    The present work is a comparative evaluation of physical and biological properties of electrospun biodegradable fibrous scaffolds based on polycaprolactone (PCL) and its blend with polycaprolactone-polyethyleneglycol-polycaprolactone (CEC) with and without nanohydroxyapatite (nHAP) particles. The fiber morphology, porosity, surface wettability, and mechanical properties of electrospun PCL were distinctly influenced by the presence of both copolymer CEC and nHAP. The degradation in hydrolytic media affected both morphological and mechanical properties of the scaffolds and the tensile strength decreased by 58% for PCL, 83% for PCL/CEC, 36% for PCL/nHAP and 75% for PCL/CEC/nHAP in 90 days of PBS ageing. MTT assay using mouse fibroblast L929 cells proved all the scaffolds to be non-cytotoxic. An overall enhanced performance was shown by PCL/CEC/nHAP scaffold in cell viability (LPH) and proliferation (Picogreen). Simultaneously, ELF assay of ALP activity (bone marker) confirmed the presence of osteogenic-induced Rabbit adipose-derived mesenchymal stem cells (ADMSCs) on all the scaffolds. In comparison, the results reveal the potential of the cytocompatible PCL/CEC/nHAP scaffold for the fabrication of living bony constructs for tissue engineering applications.

  2. Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells.

    PubMed

    Akela, Ashok; Nandi, Samit Kumar; Banerjee, Dibyajyoti; Das, Partha; Roy, Subhasis; Joardar, Siddhartha Narayan; Mandal, Mohan; Das, Pradip Kumar; Pradhan, Nisith Ranjan

    2012-10-01

    A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3). Wounds were observed for 30 days for granulation tissue formation, biochemical, histomorphological and histochemical evaluation. In this study, granulation tissue appeared significantly lesser in wounds of group 3 animals followed by group 2 and 1 animals. Neovascularisation, granulation tissue formation, denser, thicker and better arranged collagen fibres, reticulin fibres and elastin fibres formation was more in group 1 as compared with other groups. It was concluded that the application of bone marrow-derived nucleated cells into the wound margins resulted in early and significantly faster rate of complete healing as compared with buffy coat of autologous blood and autologous plasma (control). This approach may be beneficial in various surface wounds that heal at a slower rate and recommended for healing of various complicated wound in future.

  3. New approach to bone tissue engineering: simultaneous application of hydroxyapatite and bioactive glass coated on a poly(L-lactic acid) scaffold.

    PubMed

    Dinarvand, Peyman; Seyedjafari, Ehsan; Shafiee, Abbas; Jandaghi, Ali Babaei; Doostmohammadi, Ali; Fathi, Mohammad Hossein; Farhadian, Shirin; Soleimani, Masoud

    2011-11-01

    A combination of bioceramics and polymeric nanofibers holds promising potential for bone tissue engineering applications. In the present study, hydroxyapatite (HA), bioactive glass (BG), and tricalcium phosphate (TCP) particles were coated on the surface of electrospun poly(L-lactic acid) (PLLA) nanofibers, and the capacity of the PLLA, BG-PLLA, HA-PLLA, HA-BG-PLLA, and TCP-PLLA scaffolds for bone regeneration was investigated in rat critical-size defects using digital mammography, multislice spiral-computed tomography (MSCT) imaging, and histological analysis. Electrospun scaffolds exhibited a nanofibrous structure with a homogeneous distribution of bioceramics along the surface of PLLA nanofibers. A total of 8 weeks after implantation, no sign of complication or inflammation was observed at the site of the calvarial bone defect. On the basis of imaging analysis, a higher level of bone reconstruction was observed in the animals receiving HA-, BG-, and TCP-coated scaffolds compared to an untreated control group. In addition, simultaneous coating of HA and BG induced the highest regeneration among all groups. Histological staining confirmed these findings and also showed an efficient osseointegration in HA-BG-coated nanofibers. On the whole, it was demonstrated that nanofibrous structures could serve as an appropriate support to guide the healing process, and coating their surface with bioceramics enhanced bone reconstruction. These bioceramic-coated scaffolds can be used as new bone-graft substitutes capable of efficiently inducing osteoconduction and osseointegration in orthopedic fractures and defects.

  4. Strontium- and magnesium-enriched biomimetic β-TCP macrospheres with potential for bone tissue morphogenesis.

    PubMed

    Chou, J; Valenzuela, S M; Santos, J; Bishop, D; Milthorpe, B; Green, D W; Otsuka, M; Ben-Nissan, B

    2014-10-01

    During the last two decades, biogenic mineral ions have become important additives in treatments for bone regeneration and repair. Prominent among these is strontium, which is a potent suppressor of osteoclast bone resorption. Another is magnesium, which has a key influence in mineralization processes. The shells of benthic foraminiferans, hydrothermally converted into β-TCP, have been shown to effectively release a number of bone-promoting drugs at clinically relevant levels. In this study we characterized the effects of converted foraminiferan calcium dissolution and the concomitant release profile of intrinsic strontium and magnesium. We tested the effects of strontium- and magnesium-enriched macrospheres on human osteoblast (SaOS-2) and monocytoid (U937) cell lines, which can be induced to express equivalent phagocytic activities to osteoclasts. On dissolution in a biomimetic physiological solution, the macrospheres released biologically significant quantities of calcium and phosphate ions in the first 18 days. At 3 days, during which biogenic mineral ions are released, the number of U937 osteoclast-like monocyte cells decreased, while 4 days later the osteoblast cell number increased. These results show that strontium and magnesium naturally enriched macrospheres are capable of altering the metabolic activities of the cells regulating bone homeostasis. These unique macrospheres are natural origin bone void filler particles that resorb, and release physiologically significant levels of incorporated strontium, magnesium and calcium, which together make a uniquely multifunctional in situ remedy for bone regeneration and repair and the treatment of bone-wasting diseases.

  5. Enzymatically synthesized inorganic polymers as morphogenetically active bone scaffolds: application in regenerative medicine.

    PubMed

    Wang, Xiaohong; Schröder, Heinz C; Müller, Werner E G

    2014-01-01

    In recent years a paradigm shift in understanding of human bone formation has occurred that starts to change current concepts in tissue engineering of bone and cartilage. New discoveries revealed that fundamental steps in biomineralization are enzyme driven, not only during hydroxyapatite deposition, but also during initial bioseed formation, involving the transient deposition and subsequent transformation of calcium carbonate to calcium phosphate mineral. The principal enzymes mediating these reactions, carbonic anhydrase and alkaline phosphatase, open novel targets for pharmacological intervention of bone diseases like osteoporosis, by applying compounds acting as potential activators of these enzymes. It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.

  6. Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

    PubMed

    Chen, Guobao; Lv, Yonggang

    2015-01-01

    Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

  7. Potential of Raman spectroscopy for evaluation of bone quality in osteoporosis patients: results of a prospective study

    NASA Astrophysics Data System (ADS)

    Mandair, Gurjit S.; Esmonde-White, Francis W. L.; Akhter, Mohammed P.; Swift, Aaron M.; Kreider, Jaclynn; Goldstein, Steven A.; Recker, Robert R.; Morris, Michael D.

    2010-02-01

    As part of our ongoing assessment of bone tissue composition and structure, we report the first experimental protocols of a prospective study to investigate the potential of using Raman spectroscopy to diagnose and predict skeletal fragility in postmenopausal osteoporosis patients. This multi-center study will assess several potential spectroscopic and X-ray based diagnostic techniques. One hundred and twenty participants will be enrolled in this five year study and the investigators will be blinded to information concerning patient history and status. Iliac crest bone biopsy specimens are provided with no identifying information except a patient study number. Our team will use micro-computed tomography (micro-CT) to identify regions of interest in both cortical and cancellous bone from specimens delivered to us. Raman mapping will be performed using a line-focused 785 nm laser in order to obtain local and averaged values on several spectroscopic metrics of bone quality. These metrics include carbonate/phosphate and phosphate/matrix ratios. Results from an initial set of biopsies will be presented. Protocols for obtaining measurements are discussed, with emphasis on the challenges presented by the use of fixed and polymer embedded specimens. These protocols are illustrated will data from a biopsy specimen.

  8. Plasma focus: Present status and potential applications

    SciTech Connect

    Brzosko, J.S.; Nardi, V.; Powell, C.

    1997-12-01

    Initially, dense plasma focus (DPF) machines were constructed independently by Filippov in Moscow and Mather in Los Alamos at the end of the 1950s. Since then, more than 30 laboratories have carried vigorous DPF programs, oriented mainly toward the studies of physics of ion acceleration and trapping in the plasma focus environment. Applications of the DPF as intense neutron and X-ray sources have been recognized since its discovery but not implemented for various reasons. Recently, some groups (including AES) addressed the issue of DPF applications, and some of them are briefly discussed in this paper.

  9. Mesenchymal stem cells for bone repair and metabolic bone diseases.

    PubMed

    Undale, Anita H; Westendorf, Jennifer J; Yaszemski, Michael J; Khosla, Sundeep

    2009-10-01

    Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases.

  10. Mesenchymal Stem Cells for Bone Repair and Metabolic Bone Diseases

    PubMed Central

    Undale, Anita H.; Westendorf, Jennifer J.; Yaszemski, Michael J.; Khosla, Sundeep

    2009-01-01

    Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases. PMID:19797778

  11. Self bone graft and simultaneous application of implants in upper jawbone.

    PubMed

    Velasquez, P Vittorini; Falisi, G; Galli, M

    2009-10-01

    The implant supported rehabilitation of upper back sectors, sometimes, is conditioned to the pneumatization of the jawbone and so, reducing the possibility to apply the implants when the bone portion is inferior to 4 mm (important condition for the primary stability).The great rise of the jawbone and the simultaneous application of implants is, surely, the condition to have the best success guarantees compared to the only application of filling material.The surgical technologies used in the self bone grafts are various (Ilium crest, calvaria, fibula) and so also for implant applications.In this article we want to put in evidence a new technology in order to reduce at the minimum the invasive surgery of the removal and the patient morbidity.It has been executed a longitudinal study on 21 consecutive cases and illustrated by a clinical one; the success was of 94.5%. The advantages of this technique are: Functional and anatomical recovery of the jaw cavityImmediate application of implants with a thickness of remaining bone in fervor to 4 mm.Reduction of surgical timesReduced morbidity of the patientLocal an anesthesia.

  12. A tribological and biomimetic study of potential bone joint repair materials

    NASA Astrophysics Data System (ADS)

    Ribeiro, Rahul

    This research investigates materials for bone-joint failure repair using tribological and biomimicking approaches. The materials investigated represent three different repairing strategies. Refractory metals with and without treatment are candidates for total joint replacements due to their mechanical strength, high corrosion resistance and biocompatibility. A composite of biodegradable polytrimethylene carbonate, hydroxyl apatite, and nanotubes was investigated for application as a tissue engineering scaffold. Non-biodegradable polymer polyimide combined with various concentrations of nanotubes was investigated as a cartilage replacement material. A series of experimental approaches were used in this research. These include analysis of material surfaces and debris using high-resolution techniques and tribological experiments, as well as evaluation of nanomechanical properties. Specifically, the surface structure and wear mechanisms were investigated using a scanning electron microscope and an atomic force microscope. Debris morphology and structure was investigated using a transmission electron microscope. The debris composition was analyzed using an X-ray diffractometer. Nanoindentation was incorporated to investigate the surface nanomechanical properties. Polytrimythelene carbonate combined with hydroxyapatite and nanotubes exhibited a friction coefficient lower than UHMWPE. The nanoindentation response mimicked cartilage more closely than UHMWPE. A composite formed with PI and nanotubes showed a varying friction coefficient and varying nanoindentation response with variation in nanotube concentration. Low friction coefficients corresponded with low modulus values. A theory was proposed to explain this behavior based on surface interactions between nanotubes and between nanotubes and PI. A model was developed to simulate the modulus as a function of nanotube concentration. The boronized refractory metals exhibited brittleness and cracking. Higher friction

  13. Preclinical evidence of potential craniofacial adverse effect of zoledronic acid in pediatric patients with bone malignancies.

    PubMed

    Lézot, Frédéric; Chesneau, Julie; Battaglia, Séverine; Brion, Régis; Castaneda, Beatriz; Farges, Jean-Christophe; Heymann, Dominique; Rédini, Françoise

    2014-11-01

    High doses of zoledronic acid (ZOL), one of the most potent inhibitors of bone resorption, are currently evaluated in phase III clinical trials in Europe for the treatment of malignant pediatric primary bone tumors. The impact of such an intensive treatment on the craniofacial skeleton growth is a critical question in the context of patients with actively growing skeleton; in particular, in light of our previous studies evidencing that endochondral bone formation was transiently disturbed by high doses of ZOL. Two protocols adapted from pediatric treatments were developed for newborn mice (a total of 5 or 10 injections of ZOL 50μg/kg every two days). Their impact on skull bones and teeth growth was analyzed by X-rays, microCT and histology up to 3months after the last injection. ZOL administrations induced a transient delay of skull bone growth and an irreversible delay in incisor, first molar eruption and root elongation. Other teeth were affected, but most were erupted by 3months. Root histogenesis was severely impacted for all molars and massive odontogenic tumor-like structures were observed in all mandibular incisors. High doses of ZOL irreversibly disturbed teeth eruption and elongation, and delayed skull bone formation. These preclinical observations are essential for the follow-up of onco-pediatric patients treated with ZOL.

  14. Bone and skeletal muscle: Key players in mechanotransduction and potential overlapping mechanisms.

    PubMed

    Goodman, Craig A; Hornberger, Troy A; Robling, Alexander G

    2015-11-01

    The development and maintenance of skeletal muscle and bone mass is critical for movement, health and issues associated with the quality of life. Skeletal muscle and bone mass are regulated by a variety of factors that include changes in mechanical loading. Moreover, bone mass is, in large part, regulated by muscle-derived mechanical forces and thus by changes in muscle mass/strength. A thorough understanding of the cellular mechanism(s) responsible for mechanotransduction in bone and skeletal muscle is essential for the development of effective exercise and pharmaceutical strategies aimed at increasing, and/or preventing the loss of, mass in these tissues. Thus, in this review we will attempt to summarize the current evidence for the major molecular mechanisms involved in mechanotransduction in skeletal muscle and bone. By examining the differences and similarities in mechanotransduction between these two tissues, it is hoped that this review will stimulate new insights and ideas for future research and promote collaboration between bone and muscle biologists.(1).

  15. Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential

    PubMed Central

    Worthley, Daniel L.; Churchill, Michael; Compton, Jocelyn T.; Tailor, Yagnesh; Rao, Meenakshi; Si, Yiling; Levin, Daniel; Schwartz, Matthew G.; Uygur, Aysu; Hayakawa, Yoku; Gross, Stefanie; Renz, Bernhard W.; Setlik, Wanda; Martinez, Ashley N.; Chen, Xiaowei; Nizami, Saqib; Lee, Heon Goo; Kang, H. Paco; Caldwell, Jon-Michael; Asfaha, Samuel; Westphalen, C. Benedikt; Graham, Trevor; Jin, Guangchun; Nagar, Karan; Wang, Hongshan; Kheirbek, Mazen A.; Kolhe, Alka; Carpenter, Jared; Glaire, Mark; Nair, Abhinav; Renders, Simon; Manieri, Nicholas; Muthupalani, Sureshkumar; Fox, James G.; Reichert, Maximilian; Giraud, Andrew S.; Schwabe, Robert F.; Pradere, Jean-Phillipe; Walton, Katherine; Prakash, Ajay; Gumucio, Deborah; Rustgi, Anil K.; Stappenbeck, Thaddeus S.; Friedman, Richard A.; Gershon, Michael D.; Sims, Peter; Grikscheit, Tracy; Lee, Francis Y.; Karsenty, Gerard; Mukherjee, Siddhartha; Wang, Timothy C.

    2014-01-01

    The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs). PMID:25594183

  16. Bone and Skeletal Muscle: Key Players in Mechanotransduction and Potential Overlapping Mechanisms

    PubMed Central

    Goodman, Craig A.; Hornberger, Troy A.; Robling, Alexander G.

    2015-01-01

    The development and maintenance of skeletal muscle and bone mass is critical for movement, health and issues associated with the quality of life. Skeletal muscle and bone mass are regulated by a variety of factors that include changes in mechanical loading. Moreover, bone mass is, in large part, regulated by muscle-derived mechanical forces and thus by changes in muscle mass/strength. A thorough understanding of the cellular mechanism(s) responsible for mechanotransduction in bone and skeletal muscle is essential for the development of effective exercise and pharmaceutical strategies aimed at increasing, and/or preventing the loss of, mass in these tissues. Thus, in this review we will attempt to summarize the current evidence for the major molecular mechanisms involved in mechanotransduction in skeletal muscle and bone. By examining the differences and similarities in mechanotransduction between these two tissues, it is hoped that this review will stimulate new insights and ideas for future research and promote collaboration between bone and muscle biologists. PMID:26453495

  17. Sustained delivery of biomolecules from gelatin carriers for applications in bone regeneration.

    PubMed

    Song, Jiankang; Leeuwenburgh, Sander Cg

    2014-08-01

    Local delivery of therapeutic biomolecules to stimulate bone regeneration has matured considerably during the past decades, but control over the release of these biomolecules still remains a major challenge. To this end, suitable carriers that allow for tunable spatial and temporal delivery of biomolecules need to be developed. Gelatin is one of the most widely used natural polymers for the controlled and sustained delivery of biomolecules because of its biodegradability, biocompatibility, biosafety and cost-effectiveness. The current study reviews the applications of gelatin as carriers in form of bulk hydrogels, microspheres, nanospheres, colloidal gels and composites for the programmed delivery of commonly used biomolecules for applications in bone regeneration with a specific focus on the relationship between carrier properties and delivery characteristics.

  18. High frequency bone conduction auditory evoked potentials in the guinea pig: Assessing cochlear injury after ossicular chain manipulation.

    PubMed

    Bergin, M J; Bird, P A; Vlajkovic, S M; Thorne, P R

    2015-12-01

    Permanent high frequency (>4 kHz) sensorineural hearing loss following middle ear surgery occurs in up to 25% of patients. The aetiology of this loss is poorly understood and may involve transmission of supra-physiological forces down the ossicular chain to the cochlea. Investigating the mechanisms of this injury using animal models is challenging, as evaluating cochlear function with evoked potentials is confounded when ossicular manipulation disrupts the normal air conduction (AC) pathway. Bone conduction (BC) using clinical bone vibrators in small animals is limited by poor transducer output at high frequencies sensitive to trauma. The objectives of the present study were firstly to evaluate a novel high frequency bone conduction transducer with evoked auditory potentials in a guinea pig model, and secondly to use this model to investigate the impact of middle ear surgical manipulation on cochlear function. We modified a magnetostrictive device as a high frequency BC transducer and evaluated its performance by comparison with a calibrated AC transducer at frequencies up to 32 kHz using the auditory brainstem response (ABR), compound action potential (CAP) and summating potential (SP). To mimic a middle ear traumatising stimulus, a rotating bur was brought in to contact with the incudomalleal complex and the effect on evoked cochlear potentials was observed. BC-evoked potentials followed the same input-output function pattern as AC potentials for all ABR frequencies. Deterioration in CAP and SP thresholds was observed after ossicular manipulation. It is possible to use high frequency BC to evoke responses from the injury sensitive basal region of the cochlea and so not rely on AC with the potential confounder of conductive hearing loss. Ongoing research explores how these findings evolve over time, and ways in which injury may be reduced and the cochlea protected during middle ear surgery.

  19. Potential applications for halloysite nanotubes based drug delivery systems

    NASA Astrophysics Data System (ADS)

    Sun, Lin

    Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery. In this study, a drug delivery system was built based on halloysite via three different fabrication methods: physical adsorption, vacuum loading and layer-by-layer coating. Methotrexate was used as the model drug. Factors that may affect performance in both drug loading and release were tested. Results showed that methotrexate could be incorporated within the HNTs system and released in a sustained manner. Layer-by-layer coating showed a better potential than the other two methods in both MTX loading and release. Besides, lower pH could greatly improve MTX loading and release while the increased number of polyelectrolytes bilayers had a limited impact. Osteosarcoma is the most common primary bone malignancy in children and adolescents. Postoperative recurrence and metastasis has become one of the leading causes for patient death after surgical remove of the tumor mass. A strategy could be a sustained release of chemotherapeutics directly at the primary tumor sites where recurrence would mostly occur. Then, this HNTs based system was tested with osteosarcoma cells in vitro to show the potential of delivering chemotherapeutics in the treatment of osteosarcoma. Methotrexate was incorporated within HNTs with a layer-bylayer coating technique, and drug coated HNTs were filled into nylon-6 which is a common material for surgical sutures in industry. Results showed that (1) methotrexate

  20. Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine

    PubMed Central

    Li, Guanqun; Liu, Xujun; Du, Qian; Gao, Mei

    2015-01-01

    The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. PMID:26283705

  1. Spaceflight-relevant types of ionizing radiation and cortical bone: Potential LET effect?

    PubMed Central

    Lloyd, Shane A.J.; Bandstra, Eric R.; Travis, Neil D.; Nelson, Gregory A.; Bourland, J. Daniel; Pecaut, Michael J.; Gridley, Daila S.; Willey, Jeffrey S.; Bateman, Ted A.

    2008-01-01

    Extended exposure to microgravity conditions results in significant bone loss. Coupled with radiation exposure, this phenomenon may place astronauts at a greater risk for mission-critical fractures. In a previous study, we identified a profound and prolonged loss of trabecular bone (29−39%) in mice following exposure to an acute, 2 Gy dose of radiation simulating both solar and cosmic sources. However, because skeletal strength depends on trabecular and cortical bone, accurate assessment of strength requires analysis of both bone compartments. The objective of the present study was to examine various properties of cortical bone in mice following exposure to multiple types of spaceflight-relevant radiation. Nine-week old, female C57BL/6 mice were sacrificed 110 days after exposure to a single, whole body, 2 Gy dose of gamma, proton, carbon, or iron radiation. Femora were evaluated with biomechanical testing, microcomputed tomography, quantitative histomorphometry, percent mineral content, and micro-hardness analysis. Compared to non-irradiated controls, there were significant differences compared to carbon or iron radiation for only fracture force, medullary area and mineral content. A greater differential effect based on linear energy transfer (LET) level may be present: high-LET (carbon or iron) particle irradiation was associated with a decline in structural properties (maximum force, fracture force, medullary area, and cortical porosity) and mineral composition compared to low-LET radiation (gamma and proton). Bone loss following irradiation appears to be largely specific to trabecular bone and may indicate unique biological microenvironments and microdosimetry conditions. However, the limited time points examined and non-haversian skeletal structure of the mice employed highlight the need for further investigation. PMID:19122806

  2. Spaceflight-relevant types of ionizing radiation and cortical bone: Potential LET effect?

    NASA Astrophysics Data System (ADS)

    Lloyd, Shane A. J.; Bandstra, Eric R.; Travis, Neil D.; Nelson, Gregory A.; Bourland, J. Daniel; Pecaut, Michael J.; Gridley, Daila S.; Willey, Jeffrey S.; Bateman, Ted A.

    2008-12-01

    Extended exposure to microgravity conditions results in significant bone loss. Coupled with radiation exposure, this phenomenon may place astronauts at a greater risk for mission-critical fractures. In a previous study, we identified a profound and prolonged loss of trabecular bone (29-39%) in mice following exposure to an acute, 2 Gy dose of radiation simulating both solar and cosmic sources. However, because skeletal strength depends on trabecular and cortical bone, accurate assessment of strength requires analysis of both bone compartments. The objective of the present study was to examine various properties of cortical bone in mice following exposure to multiple types of spaceflight-relevant radiation. Nine-week old, female C57BL/6 mice were sacrificed 110 days after exposure to a single, whole body, 2 Gy dose of gamma, proton, carbon, or iron radiation. Femora were evaluated with biomechanical testing, microcomputed tomography, quantitative histomorphometry, percent mineral content, and micro-hardness analysis. Compared to non-irradiated controls, there were significant differences compared to carbon or iron radiation for only fracture force, medullary area and mineral content. A greater differential effect based on linear energy transfer (LET) level may be present: high-LET (carbon or iron) particle irradiation was associated with a decline in structural properties (maximum force, fracture force, medullary area, and cortical porosity) and mineral composition compared to low-LET radiation (gamma and proton). Bone loss following irradiation appears to be largely specific to trabecular bone and may indicate unique biological microenvironments and microdosimetry conditions. However, the limited time points examined and non-haversian skeletal structure of the mice employed highlight the need for further investigation.

  3. Investigation of the mechanical properties and failure modes of hybrid natural fiber composites for potential bone fracture fixation plates.

    PubMed

    Manteghi, Saeed; Mahboob, Zia; Fawaz, Zouheir; Bougherara, Habiba

    2017-01-01

    The purpose of this study is to investigate the mechanical feasibility of a hybrid Glass/Flax/Epoxy composite material for bone fracture fixation such as fracture plates. These hybrid composite plates have a sandwich structure in which the outer layers are made of Glass/Epoxy and the core from Flax/Epoxy. This configuration resulted in a unique structure compared to prior composites proposed for similar clinical applications. In order to evaluate the mechanical properties of this hybrid composite, uniaxial tension, compression, three-point bending and Rockwell Hardness tests were conducted. In addition, water absorption tests were performed to investigate the rate of water absorption for the specimens. This study confirms that the proposed hybrid composite plates are significantly more flexible axially compared to conventional metallic plates. Furthermore, they have considerably higher ultimate strength in tension, compression and flexion. Such high strength will ensure good stability of bone-implant construct at the fracture site, immobilize adjacent bone fragments and carry clinical-type forces experienced during daily normal activities. Moreover, this sandwich structure with stronger and stiffer face sheets and more flexible core can result in a higher stiffness and strength in bending compared to tension and compression. These qualities make the proposed hybrid composite an ideal candidate for the design of an optimized fracture fixation system with much closer mechanical properties to human cortical bone.

  4. Retinal image analysis: concepts, applications and potential.

    PubMed

    Patton, Niall; Aslam, Tariq M; MacGillivray, Thomas; Deary, Ian J; Dhillon, Baljean; Eikelboom, Robert H; Yogesan, Kanagasingam; Constable, Ian J

    2006-01-01

    As digital imaging and computing power increasingly develop, so too does the potential to use these technologies in ophthalmology. Image processing, analysis and computer vision techniques are increasing in prominence in all fields of medical science, and are especially pertinent to modern ophthalmology, as it is heavily dependent on visually oriented signs. The retinal microvasculature is unique in that it is the only part of the human circulation that can be directly visualised non-invasively in vivo, readily photographed and subject to digital image analysis. Exciting developments in image processing relevant to ophthalmology over the past 15 years includes the progress being made towards developing automated diagnostic systems for conditions, such as diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity. These diagnostic systems offer the potential to be used in large-scale screening programs, with the potential for significant resource savings, as well as being free from observer bias and fatigue. In addition, quantitative measurements of retinal vascular topography using digital image analysis from retinal photography have been used as research tools to better understand the relationship between the retinal microvasculature and cardiovascular disease. Furthermore, advances in electronic media transmission increase the relevance of using image processing in 'teleophthalmology' as an aid in clinical decision-making, with particular relevance to large rural-based communities. In this review, we outline the principles upon which retinal digital image analysis is based. We discuss current techniques used to automatically detect landmark features of the fundus, such as the optic disc, fovea and blood vessels. We review the use of image analysis in the automated diagnosis of pathology (with particular reference to diabetic retinopathy). We also review its role in defining and performing quantitative measurements of vascular topography

  5. Potential Applications of Biotechnology to Aerospace Materials.

    DTIC Science & Technology

    1986-11-01

    from low - grade ores and industrial wastes. Other organisms that have demonstrated ability to solu- bilize metals include heterotrophic bacteria, molds...cadmium, scandium, erbium, yttrium, and titanium. The potential advantage of biomining is the ability to concentrate metals from low - grade materials...organisms and/ or biological molecules to produce or aid in production of a commercial product. This is a broad definition of a relatively young

  6. Thermoluminescence: Potential Applications in Forensic Science

    NASA Technical Reports Server (NTRS)

    Ingham, J. D.; Lawson, D. D.

    1973-01-01

    In crime laboratories one of the most difficult operations is to determine unequivocally whether or not two samples of evidence of the same type were originally part of the same thing or were from the same source. It has been found that high temperature thermoluminescence (room temperature to 723 K) can be used for comparisons of this type, although work to date indicates that there is generally a finite probability for coincidental matching of glass or soil samples. Further work is required to determine and attempt to minimize these probabilities for different types of materials, and to define more clearly the scope of applicability of thermoluminescence to actual forensic situations.

  7. The application of cone-beam CT in the aging of bone calluses: a new perspective?

    PubMed

    Cappella, A; Amadasi, A; Gaudio, D; Gibelli, D; Borgonovo, S; Di Giancamillo, M; Cattaneo, C

    2013-11-01

    In the forensic and anthropological fields, the assessment of the age of a bone callus can be crucial for a correct analysis of injuries in the skeleton. To our knowledge, the studies which have focused on this topic are mainly clinical and still leave much to be desired for forensic purposes, particularly in looking for better methods for aging calluses in view of criminalistic applications. This study aims at evaluating the aid cone-beam CT can give in the investigation of the inner structure of fractures and calluses, thus acquiring a better knowledge of the process of bone remodeling. A total of 13 fractures (three without callus formation and ten with visible callus) of known age from cadavers were subjected to radiological investigations with digital radiography (DR) (conventional radiography) and cone-beam CT with the major aim of investigating the differences between DR and tomographic images when studying the inner and outer structures of bone healing. Results showed how with cone-beam CT the structure of the callus is clearly visible with higher specificity and definition and much more information on mineralization in different sections and planes. These results could lay the foundation for new perspectives on bone callus evaluation and aging with cone-beam CT, a user-friendly and skillful technique which in some instances can also be used extensively on the living (e.g., in cases of child abuse) with reduced exposition to radiation.

  8. Ceramic/metal biocidal nanocomposites for bone-related applications.

    PubMed

    Miranda, Miriam; Fernández, Adolfo; Lopez-Esteban, Sonia; Malpartida, Francisco; Moya, José S; Torrecillas, Ramón

    2012-07-01

    Hydroxyapatite/silver nanocomposites have been designed and synthesized as an engineering material for biomedical applications. The hydroxyapatite matrix was synthesized by a sol-gel method and, subsequently, the Ag nanoparticles were deposited by heterogeneous precipitation followed by two different reduction routes: thermal or chemical. Both sets were studied and compared and, in all cases, the metal nanoparticles appear perfectly isolated and attached to the surface of the hydroxyapatite. The average metal particle size is below 10 nm, allowing an important contact surface between silver and the microorganisms. The antimicrobial behavior against common bacteria showed a high effectiveness, well above the commercial level, as well as against yeast, in the case of the chemically reduced sample. Due to the nanocomposite microstructure, only a negligible portion of metal was released to the lixiviated liquid after the biocide tests, minimizing the risk of toxicity. These nanocomposites offer a solution to the infections on the surface of implants, one of the main problems in reaching a suitable level of osseointegration.

  9. TU-CD-BRA-11: Application of Bone Suppression Technique to Inspiratory/expiratory Chest Radiography

    SciTech Connect

    Tanaka, R; Sanada, S; Sakuta, K; Kawashima, H; Kishitani, Y

    2015-06-15

    with the bone suppression technique has potential for predicting local lung function on the basis of dynamic analysis of pulmonary markings. This work was partially supported by Nakatani Foundation, Grant-in-aid for Scientific Research (C) of Ministry of Education, Culture, Sports, Science and Technology, JAPAN (Grant number : 24601007), and Nakatani Foundation, Mitsubishi Foundation, and the he Mitani Foundation for Research and Development. Yasushi Kishitani is a staff of TOYO corporation.

  10. Potential clinical applications of quantum dots.

    PubMed

    Medintz, Igor L; Mattoussi, Hedi; Clapp, Aaron R

    2008-01-01

    The use of luminescent colloidal quantum dots in biological investigations has increased dramatically over the past several years due to their unique size-dependent optical properties and recent advances in biofunctionalization. In this review, we describe the methods for generating high-quality nanocrystals and report on current and potential uses of these versatile materials. Numerous examples are provided in several key areas including cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. We also explore toxicity issues surrounding these materials and speculate about the future uses of quantum dots in a clinical setting.

  11. Potentiation of osteoclastogenesis by adipogenic conversion of bone marrow-derived mesenchymal stem cells.

    PubMed

    Mori, Keisuke; Suzuki, Keiji; Hozumi, Akira; Goto, Hisataka; Tomita, Masato; Koseki, Hironobu; Yamashita, Shunichi; Osaki, Makoto

    2014-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) are the indispensable component of the bone marrow, being the common precursors for adipocytes and osteoblasts. We show here that adipogenic differentiation resulted in increase in the production of adipocyte markers, such as adiponectin,fatty-acid binding proteins (FABP4), peroxisome proliferator-activated receptor γ (PPARγ), as well as the receptor activator of nuclear-κB ligand (RANKL). Co-culture of osteoclast precursors (OCPs) with BMSCs-derived adipocytes significantly enhanced osteoclast differentiation with low-dose RANKL, whose levels alone could not promote osteoclastogenesis. These results demonstrate for the first time that adipogenic differentiation of BMSCs plays a pivotal role in maintaining bone homeostasis.

  12. Antarctic Yeasts: Biodiversity and Potential Applications

    NASA Astrophysics Data System (ADS)

    Shivaji, S.; Prasad, G. S.

    This review is an attempt in cataloguing the diversity of yeasts in Antarctica, highlight their biotechnological potential and understand the basis of adaptation to low temperature. As of now several psychrophilic and psychrotolerant yeasts from Antarctic soils and marine waters have been characterized with respect to their growth characteristics, ecological distribution and taxonomic significance. Interestingly most of these species belonged to basidiomycetous yeasts which as a group are known for their ability to circumvent and survive under stress conditions. Simultaneously their possible role as work horses in the biotechnological industry was recognized due to their ability to produce novel enzymes and biomolecules such as agents for the breakdown of xenobiotics, and novel pharmaceutical chemi cals. The high activity of psychrophilic enzymes at low and moderate temperatures offers potential economic benefits. As of now lipases from Pseudozyma antarctica have been extensively studied to understand their unique thermal stability at 90°C and also because of its use in the pharmaceutical, agriculture, food, cosmetics and chemical industry. A few of the other enzymes which have been studied include extracellular alpha-amylase and glucoamylase from the yeast Pseudozyma antarctica (Candida antarctica), an extra-cellular protease from Cryptococcus humicola, an aspartyl proteinase from Cryptococcus humicola, a novel extracellular subtilase from Leucosporidium antarcticum, and a xylanase from Cryptococcus adeliensis

  13. Algal Cell Factories: Approaches, Applications, and Potentials

    PubMed Central

    Fu, Weiqi; Chaiboonchoe, Amphun; Khraiwesh, Basel; Nelson, David R.; Al-Khairy, Dina; Mystikou, Alexandra; Alzahmi, Amnah; Salehi-Ashtiani, Kourosh

    2016-01-01

    With the advent of modern biotechnology, microorganisms from diverse lineages have been used to produce bio-based feedstocks and bioactive compounds. Many of these compounds are currently commodities of interest, in a variety of markets and their utility warrants investigation into improving their production through strain development. In this review, we address the issue of strain improvement in a group of organisms with strong potential to be productive “cell factories”: the photosynthetic microalgae. Microalgae are a diverse group of phytoplankton, involving polyphyletic lineage such as green algae and diatoms that are commonly used in the industry. The photosynthetic microalgae have been under intense investigation recently for their ability to produce commercial compounds using only light, CO2, and basic nutrients. However, their strain improvement is still a relatively recent area of work that is under development. Importantly, it is only through appropriate engineering methods that we may see the full biotechnological potential of microalgae come to fruition. Thus, in this review, we address past and present endeavors towards the aim of creating productive algal cell factories and describe possible advantageous future directions for the field. PMID:27983586

  14. Microwave processing of lunar materials: potential applications

    SciTech Connect

    Meek, T.T.; Cocks, F.H.; Vaniman, D.T.; Wright, R.A.

    1984-01-01

    The microwave processing of lunar materials holds promise for the production of either water, oxygen, primary metals, or ceramic materials. Extra high frequency microwave (EHF) at between 100 and 500 gigahertz have the potential for selective coupling to specific atomic species and a concomitant low energy requirement for the extraction of specific materials, such as oxygen, from lunar ores. The coupling of ultra high frequency (UHF) (e.g., 2.45 gigahertz) microwave frequencies to hydrogen-oxygen bonds might enable the preferential and low energy cost removal (as H/sub 2/O) of implanted protons from the sun or of adosrbed water which might be found in lunar dust in permanently shadowed polar areas. Microwave melting and selective phase melting of lunar materials could also be used either in the preparation of simplified ceramic geometries (e.g., bricks) with custom-tailored microstructures, or for the direct preparation of hermetic walls in underground structures. Speculatively, the preparation of photovoltaic devices based on lunar materials, especially ilmenite, may be a potential use of microwave processing on the moon. Preliminary experiments on UHF melting of terrestrial basalt, basalt/ilmenite and mixtures show that microwave processing is feasible.

  15. Algal Cell Factories: Approaches, Applications, and Potentials.

    PubMed

    Fu, Weiqi; Chaiboonchoe, Amphun; Khraiwesh, Basel; Nelson, David R; Al-Khairy, Dina; Mystikou, Alexandra; Alzahmi, Amnah; Salehi-Ashtiani, Kourosh

    2016-12-13

    With the advent of modern biotechnology, microorganisms from diverse lineages have been used to produce bio-based feedstocks and bioactive compounds. Many of these compounds are currently commodities of interest, in a variety of markets and their utility warrants investigation into improving their production through strain development. In this review, we address the issue of strain improvement in a group of organisms with strong potential to be productive "cell factories": the photosynthetic microalgae. Microalgae are a diverse group of phytoplankton, involving polyphyletic lineage such as green algae and diatoms that are commonly used in the industry. The photosynthetic microalgae have been under intense investigation recently for their ability to produce commercial compounds using only light, CO₂, and basic nutrients. However, their strain improvement is still a relatively recent area of work that is under development. Importantly, it is only through appropriate engineering methods that we may see the full biotechnological potential of microalgae come to fruition. Thus, in this review, we address past and present endeavors towards the aim of creating productive algal cell factories and describe possible advantageous future directions for the field.

  16. Bone marrow-derived mesenchymal stem cell plasticity and their application perspectives.

    PubMed

    Menabde, G; Gogilashvili, K; Kakabadze, Z; Berishvili, E

    2009-02-01

    The aim of this review is to summarize recent developments in research on the characteristics of bone marrow-derived mesenchymal stem cell plasticity. Stem cells are uncommitted entities capable of both self-renewal and differentiation into multiple cell lineages. In general, there are certain types of stem cell populations that are identified from embryonic and postnatal tissues. Embryonic stem cells are derived from mammalian blastocytes and theoretically have the ability to generate differentiated cell types arising from the three germ layers: mesoderm, ectoderm and endoderm. In contrast, postnatal stem cells are thought to be tissue specific, committed precursors capable of developing into a restricted number of cell lineages. Bone marrow stromal stem cells (BMSSCs), also known as mesenchymal stem cells, have been identified as a population of organized hierarchical postnatal stem cells with the potential to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, myoblasts and neural cells. Recently, studies on the plasticity of BMSSCs challenge the traditional dogma that the differentiation and commitment of postnatal stem cells are limited to cell populations resident in their local environment. Current boneregenerative techniques, such as autologous bone grafting, allografts and alloplastic materials, have limitations that hinder their use in a wider range of clinical conditions. Hence, the development of improved methods, such as BMSSC-mediated bone regeneration, is necessary for achieving future viable therapeutic alternatives.

  17. Polymer recycling: potential application of radiation technology

    NASA Astrophysics Data System (ADS)

    Burillo, Guillermina; Clough, Roger L.; Czvikovszky, Tibor; Guven, Olgun; Le Moel, Alain; Liu, Weiwei; Singh, Ajit; Yang, Jingtian; Zaharescu, Traian

    2002-04-01

    Management of solid waste is an important problem, which is becoming progressively worse as a byproduct of continuing economic growth and development. Polymeric materials (plastics and rubbers) comprise a steadily increasing proportion of the municipal and industrial waste going into landfill. Development of technologies for reducing polymeric waste, which are acceptable from the environmental standpoint, and which are cost-effective, has proven to be a difficult challenge due to complexities inherent in the reuse of polymers. Establishing optimal processes for the reuse/recycling of polymeric materials thus remains a worldwide challenge as we enter the new century. Due to the ability of ionizing radiation to alter the structure and properties of bulk polymeric materials, and the fact that it is applicable to essentially all polymer types, irradiation holds promise for impacting the polymer waste problem. The three main possibilities for use of radiation in this application are: (1) enhancing the mechanical properties and performance of recovered materials or material blends, principally through crosslinking, or through surface modification of different phases being combined; (2) treatment causing or enhancing the decomposition of polymers, particularly through chain scission, leading to recovery of either low molecular weight mixtures, or powders, for use as chemical feedstocks or additives; (3) production of advanced polymeric materials designed for environmental compatibility. This paper provides an overview of the polymer recycling problem, describes the major technological obstacles to the implementation of recycling technologies, and outlines some of the approaches being taken. A review of radiation-based recycling research is then provided, followed by a discussion of future directions where irradiation may be relevant to the problems currently inhibiting the widespread recycling of polymeric materials.

  18. In vitro models for the evaluation of angiogenic potential in bone engineering

    PubMed Central

    Cenni, Elisabetta; Perut, Francesca; Baldini, Nicola

    2011-01-01

    Blood vessels have a fundamental role both in skeletal homeostasis and in bone repair. Angiogenesis is also important for a successful bone engineering. Therefore, scaffolds should be tested for their ability to favour endothelial cell adhesion, proliferation and functions. The type of endothelial cell to use for in vitro assays should be carefully considered, because the properties of these cells may depend on their source. Morphological and functional relationships between endothelial cells and osteoblasts are evaluated with co-cultures, but this model should still be standardized, particularly for distinguishing the two cell types. Platelet-rich plasma and recombinant growth factors may be useful for stimulating angiogenesis. PMID:21042285

  19. Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia; Katkova, Olena

    Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3Н- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bonеs metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in

  20. Sequential Treatment with SDF-1 and BMP-2 Potentiates Bone Formation in Calvarial Defects.

    PubMed

    Hwang, Hee-Don; Lee, Jung-Tae; Koh, Jeong-Tae; Jung, Hong-Moon; Lee, Heon-Jin; Kwon, Tae-Geon

    2015-07-01

    Stromal cell-derived factor-1 (SDF-1) protein and its receptor, CXCR-4, play an important role in tissue repair and regeneration in various organs, including the bone. SDF-1 is indispensable for bone morphogenetic protein-2 (BMP-2)-induced osteogenic differentiation. However, SDF-1 is not needed after the osteogenic induction has been activated. Since the precise condition for the additive effects of combined DF-1 and BMP-2 in bone healing had not been fully investigated, we aimed to determine the optimal conditions for SDF-1- and BMP-2-mediated bone regeneration. We examined the in vitro osteoblastic differentiation and cell migration after sequential treatments with SDF-1 and BMP-2. Based on the in vitro additive effects of SDF-1 and BMP-2, the critical size defects of mice calvaria were treated with these cytokines in various sequences. Phosphate buffered saline (PBS)-, SDF-1-, or BMP-2-soaked collagen scaffolds were implanted into the calvarial defects (n=36). Periodic percutaneous injections of PBS or the cytokine SDF-1 and BMP-2 into the implanted scaffolds were performed on days 3 and 6, postoperatively. Six experimental groups were used according to the types and sequences of the cytokine treatments. After 28 days, the mice were euthanized and bone formation was evaluated with microcomputed tomography and histology. The molecular mechanism of the additive effect of SDF-1 and BMP-2 was evaluated by analyzing intracellular signal transduction through Smad and Erk phosphorylation. The in vitro experiments revealed that, among all the treatments, the treatment with BMP-2 after SDF-1 showed the strongest osteoblastic differentiation and enhanced cell migration. Similarly, in the animal model, the treatment with SDF-1 followed by BMP-2 treatment showed the highest degree of new bone regeneration than any other groups, including the one with continuous BMP-2 treatment. This new bone formation can be partially explained by the activation of Smad and Erk pathways

  1. A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype.

    PubMed

    Kato, Satoshi; Sangadala, Sreedhara; Tomita, Katsuro; Titus, Louisa; Boden, Scott D

    2011-03-01

    There is an urgent need to develop methods that lower costs of using recombinant human bone morphogenetic proteins (BMPs) to promote bone induction. In this study, we demonstrate the osteogenic effect of a low-molecular weight compound, SVAK-12, that potentiated the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. Here, we report a specific compound, SVAK-12, which was selected based on in silico screenings of small-molecule databases using the homology modeled interaction motif of Smurf1-WW2 domain. The enhancement of BMP-2 activity by SVAK-12 was characterized by evaluating a BMP-specific reporter activity and by monitoring the BMP-2-induced expression of mRNA for osteocalcin and alkaline phosphatase (ALP), which are widely accepted marker genes of osteoblast differentiation. Finally, we confirmed these results by also measuring the enhancement of BMP-2-induced activity of ALP. Smurf1 is an E3 ligase that targets osteogenic Smads for ubiquitin-mediated proteasomal degradation. Smurf1 is an interesting potential target to enhance bone formation based on the positive effects on bone of proteins that block Smurf1-binding to Smad targets or in Smurf1-/- knockout mice. Since Smads bind Smurf1 via its WW2 domain, we performed in silico screening to identify compounds that might interact with the Smurf1-WW2 domain. We recently reported the activity of a compound, SVAK-3. However, SVAK-3, while exhibiting BMP-potentiating activity, was not stable and thus warranted a new search for a more stable and efficacious compound among a selected group of candidates. In addition to being more stable, SVAK-12 exhibited a dose-dependent activity in inducing osteoblastic differentiation of myoblastic C2C12 cells even when multiple markers of the osteoblastic phenotype were parallelly monitored.

  2. A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype

    PubMed Central

    Kato, Satoshi; Tomita, Katsuro; Titus, Louisa; Boden, Scott D.

    2011-01-01

    There is an urgent need to develop methods that lower costs of using recombinant human bone morphogenetic proteins (BMPs) to promote bone induction. In this study, we demonstrate the osteogenic effect of a low-molecular weight compound, SVAK-12, that potentiated the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. Here, we report a specific compound, SVAK-12, which was selected based on in silico screenings of small-molecule databases using the homology modeled interaction motif of Smurf1-WW2 domain. The enhancement of BMP-2 activity by SVAK-12 was characterized by evaluating a BMP-specific reporter activity and by monitoring the BMP-2-induced expression of mRNA for osteocalcin and alkaline phosphatase (ALP), which are widely accepted marker genes of osteoblast differentiation. Finally, we confirmed these results by also measuring the enhancement of BMP-2-induced activity of ALP. Smurf1 is an E3 ligase that targets osteogenic Smads for ubiquitin-mediated proteasomal degradation. Smurf1 is an interesting potential target to enhance bone formation based on the positive effects on bone of proteins that block Smurf1-binding to Smad targets or in Smurf1−/− knockout mice. Since Smads bind Smurf1 via its WW2 domain, we performed in silico screening to identify compounds that might interact with the Smurf1-WW2 domain. We recently reported the activity of a compound, SVAK-3. However, SVAK-3, while exhibiting BMP-potentiating activity, was not stable and thus warranted a new search for a more stable and efficacious compound among a selected group of candidates. In addition to being more stable, SVAK-12 exhibited a dose-dependent activity in inducing osteoblastic differentiation of myoblastic C2C12 cells even when multiple markers of the osteoblastic phenotype were parallelly monitored. PMID:21110071

  3. Novel 3D Tissue Engineered Bone Model, Biomimetic Nanomaterials, and Cold Atmospheric Plasma Technique for Biomedical Applications

    NASA Astrophysics Data System (ADS)

    Wang, Mian

    This thesis research is consist of four chapters, including biomimetic three-dimensional tissue engineered nanostructured bone model for breast cancer bone metastasis study (Chapter one), cold atmospheric plasma for selectively ablating metastatic breast cancer (Chapter two), design of biomimetic and bioactive cold plasma modified nanostructured scaffolds for enhanced osteogenic differentiation of bone marrow derived mesenchymal stem cells (Chapter three), and enhanced osteoblast and mesenchymal stem cell functions on titanium with hydrothermally treated nanocrystalline hydroxyapatite/magnetically treated carbon nanotubes for orthopedic applications (Chapter four). All the thesis research is focused on nanomaterials and the use of cold plasma technique for various biomedical applications.

  4. [The potential of cone beam computed tomography of the temporal bones in the patients presenting with otosclerosis].

    PubMed

    Karpishchenko, S A; Zubareva, A A; Filimonov, V N; Shavgulidze, M A; Azovtseva, E A

    The objective of the present study was to analyze the potential of cone beam computed tomography of the temporal bones in the patients presenting with otosclerosis for the detection of surgically significant specific structural features of the labyrinth wall of the tympanic cavity. More than 400 tomograms of the temporal bones were obtained with the use of a cone beam tomographwere available for the investigation during the period from 2012 till 2016. The study was carried out in several steps, viz. the search for the optimal (for the given instrument) position of the patient, the experimental stage, the retrospective analysis of the tomograms and the comparison of the temporal bones of different types (pneumatic, mixed, and sclerotic) in individual patients, the comparison of the results of cone beam computed tomography (CBCT) with the intraoperative observations, and the modification of the algorithm for the analysis of temporal bone cone beam tomograms. The study included a total of 16 patients (15 women at the age from 32 to 56 years and one managed 58 years) presenting with the clinical diagnosis of otosclerosis. The results of the study were used to elaborate the algorithm for the analysis of cone beam tomograms of the temporal bones to be performed inthe stage by stage manner including the qualitative analysis of tomograms, evaluation of their quantitative parameters and additional characteristics to be taken into consideration when planning the surgical interventions on the labyrinth wall and the tympanic cavity as a preparation for the stapedoplastic treatment. The results of CBCT obtained in the present study were compared with the surgical observations. The diagnostic sensitivity and specificity of the method were estimated to be 100% and 83% respectively. It is concluded that cone beam computed tomography can be employed as a component of the diagnostic algorithm prior to the planning of surgical interventions onthe medial wall of the tympanic cavity

  5. Marine Origin Collagens and Its Potential Applications

    PubMed Central

    Silva, Tiago H.; Moreira-Silva, Joana; Marques, Ana L. P.; Domingues, Alberta; Bayon, Yves; Reis, Rui L.

    2014-01-01

    Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role, existing different types according with their specific organization in distinct tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches. Also, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are from bovine and porcine origin, but other ways are making their route, such as recombinant production, but also extraction from marine organisms like fish. Different organisms have been proposed and explored for collagen extraction, allowing the sustainable production of different types of collagens, with properties depending on the kind of organism (and their natural environment) and extraction methodology. Such variety of collagen properties has been further investigated in different ways to render a wide range of applications. The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation. PMID:25490254

  6. Periarticular osteopenia in adjuvant induced arthritis: role of interleukin-1 in decreased osteogenic and increased resorptive potential of bone marrow cells.

    PubMed Central

    Suzuki, Y; Tanihara, M; Ichikawa, Y; Osanai, A; Nakagawa, M; Ide, M; Mizushima, Y

    1995-01-01

    OBJECTIVE--To clarify the local osteogenic and bone resorptive potential of periarticular bone in adjuvant induced arthritis (AIA). METHODS--Formation of fibroblast colony forming units (FCFU; osteogenic precursor cells) and osteoclast-like cells in bone marrow culture was studied in AIA rats. Osteoclast-inducing activity in the AIA rat bone marrow was assayed by the addition of the marrow supernatant from rats with AIA to control cultures. Bone mineral density was determined by dual x ray absorptiometry. RESULTS--Marrow from AIA rats and that from animals receiving recombinant human interleukin-1 (IL-1) beta for seven days grew significantly fewer FCFU than control marrow. Formation of osteoclast-like cells was increased in bone marrow cultures from rats with AIA, especially when bone marrow cells were cultured in the presence of marrow supernatant. Formation of resorption lacunae on ivory slices was increased in the marrow cultures from rats with AIA, especially from the right (adjuvant inoculated) tibia. AIA rat marrow supernatant promoted osteoclast-like cell formation in control culture, and this was significantly suppressed by an anti-IL-1 antibody. Rats with AIA showed a significant decrease in the bone mineral density of the periarticular regions of the tibia and femur. CONCLUSION--An uncoupled state in bone resorption-formation linkage, possibly mediated through an increase of IL-1 in the bone marrow, may contribute to the development of periarticular osteopenia in inflammatory arthritis. Images PMID:7632091

  7. Potential effect of angiotensin II receptor blockade in adipose tissue and bone.

    PubMed

    Nakagami, Hironori; Osako, Mariana Kiomy; Morishita, Ryuichi

    2013-01-01

    Recent evidence demonstrated that dysregulation of adipocytokine functions seen in abdominal obesity may be involved in the pathogenesis of the metabolic syndrome. Angiotensinogen, the precursor of angiotensin (Ang) II, is produced primarily in the liver, and also in adipose tissue, where it is up-regulated during the development of obesity and involved in blood pressure regulation and adipose tissue growth. Blockade of renin-angiotensin system (RAS) attenuates weight gain and adiposity by enhanced energy expenditure, and the favorable metabolic effects of telmisartan have been related to its Ang II receptor blockade and action as a partial agonist of peroxisome proliferators activated receptor (PPAR)-γ. PPARγ plays an important role in regulating carbohydrate and lipid metabolism, and ligands for PPARγ can improve insulin sensitivity and reduce triglyceride levels. Similarly, bone metabolism is closely regulated by hormones and cytokines, which have effects on both bone resorption and deposition. It is known that the receptors of Ang II are expressed in culture osteoclasts and osteoblasts, and Ang II is postulated to be able to act upon the cells involved in bone metabolism. In in vitro system, Ang II induced the differentiation and activation of osteoclasts responsible for bone resorption. Importantly, it was demonstrated by the sub-analysis of a recent clinical study that the fracture risk was significantly reduced by the usage of angiotensin-converting enzyme inhibitors. To treat the subgroups of hypertensive patients with osteoporosis RAS can be considered a novel target.

  8. Differentiation potential and GFP labeling of sheep bone marrow-derived mesenchymal stem cells.

    PubMed

    Czernik, Marta; Fidanza, Antonella; Sardi, Martina; Galli, Cesare; Brunetti, Dario; Malatesta, Daniela; Della Salda, Leonardo; Matsukawa, Kazutsugu; Ptak, Grazyna E; Loi, Pasqualino

    2013-01-01

    Mesenchymal stem cells (MSCs) are an important cell population in the bone marrow microenvironment. MSCs have the capacity to differentiate in vitro into several mesenchymal tissues including bone, cartilage, fat, tendon, muscle, and marrow stroma. This study was designed to isolate, expand, and characterize the differentiation ability of sheep bone marrow-derived MSCs and to demonstrate the possibility to permanently express a reporter gene. Bone marrow was collected from the iliac crest and mononuclear cells were separated by density gradient centrifugation. Sheep MSCs cell lines were stable characterized as CD44+ and CD34- and then transfected with a green fluorescent protein (GFP) reporter gene. The GFP expression was maintained in about half (46.6%) of cloned blastocysts produced by nuclear transfer of GFP+ sheep MSCs, suggesting the possibility to establish multipotent embryonic cells' lines carrying the fluorescent tag for comparative studies on the differentiation capacity of adult stem cells (MSCs) versus embryonic stem cells. We found that sheep MSCs under appropriate culture conditions could be induced to differentiate into adipocytes, chondrocytes, and osteoblast lineages. Our results confirm the plasticity of sheep MSCs and establish the foundation for the development of a pre-clinical sheep model to test the efficiency and safety of cell replacement therapy.

  9. Denosumab-Treated Giant Cell Tumor of Bone Its Histologic Spectrum and Potential Diagnostic Pitfalls.

    PubMed

    Roitman, Pablo Daniel; Jauk, Federico; Farfalli, Germán Luis; Albergo, José Ignacio; Aponte-Tinao, Luis Alberto

    2017-02-21

    Giant cell tumor of bone (GCT) is a locally aggressive, rarely metastasizing primary bone neoplasm that occurs most frequently in the epiphysis of long bones of young adults. It is composed of round, oval or elongated mononuclear cells admixed with osteoclast-like giant cells that express receptor activator of nuclear factor- қB (RANK). The mononuclear stromal cells express RANK ligand (RANKL), a mediator of osteoclast activation. Denosumab, a monoclonal antibody that inhibits RANKL reducing tumor-associated bone lysis, has been used to treat selected cases of GCT. We reviewed the clinical records and histologic slides of 9 patients with GCT that had received denosumab therapy and were subsequently surgically treated. There were 5 males and 4 females, aged 20 to 66 (mean 36). Duration of treatment varied from 2,5 to 13months (mean 5,9). In all cases, different degrees of ossification, fibrosis, depletion of giant cells and proliferation of mononuclear cells were seen. With this combination of changes, denosumab-treated GCT may mimick other lesions such as fibrous dysplasia, juvenile ossifying fibroma, nonossifying fibroma and osteoblastoma. Less frequent but more relevant is the presence of cellular atypia or patterns of ossification that resemble an undifferentiated pleomorphic sarcoma, a conventional osteosarcoma or a low-grade central osteosarcoma. The presence of clinical and radiological response to denosumab along with the lack of high mitotic activity, atypical mitotic figures, extensive necrosis or a permeative pattern of growth, represent clues to achieve a correct diagnosis.

  10. Variations of oxygen and hydrogen isotope ratios in deer bones and their potential in paleoclimatology

    SciTech Connect

    Luz, B.; Schwarcz, H.P.; Cormie, A.B.

    1985-01-01

    Variations of deltaO-18 of bone phosphate (deltap) and deltaD of bone collagen of white tailed deer, were studied in samples with wide geographic distribution in North America. There is a linear relationship between deltaO-18 of local precipitation (deltaw) and deltap (deltap=0.54deltaw+21.53; r=0.81). Scatter about the regression line is related to estimation errors of deltaw and to changes in relative humidity. Low relative humidity results in highly O-18 enriched leaf water, which may lead to similar enrichment in bones of deer, that depend on leaves as a major source of food. Linear correlation between deltaD and deltap is high (r=0.93), suggesting that both variables depend on variations in isotopic composition of local environmental water. Samples from arid regions are highly enriched in O-18 and deviate from the regression line. This raises the possibility of estimating past changes in relative humidity by simultaneous analysis of deltap and deltaD in fossil bones.

  11. Characterisation of a new bioadhesive system based on polysaccharides with the potential to be used as bone glue.

    PubMed

    Hoffmann, Bettina; Volkmer, Elias; Kokott, Andreas; Augat, Peter; Ohnmacht, Michael; Sedlmayr, Nicole; Schieker, Matthias; Claes, Lutz; Mutschler, Wolf; Ziegler, Günter

    2009-10-01

    Although gluing bone is in theory a very attractive alternative to classical fracture treatment, this method is not yet clinically established due to the lack of an adhesive which would meet all the necessary requirements. We therefore developed a novel two-component bioadhesive system with the potential to be used as a bone adhesive based on biocompatible and degradable biopolymers (chitosan, oxidised dextran or starch). After mixing in water, the two components covalently cross-link by forming a Schiff's base. By the same mechanism, the glue binds to any other exposed amino group such as for example those exposed in fractured bone, even in the presence of water. Modified chitosan was synthesised from commercially available chitosan by deacetylation and was then reduced in molecular weight by heating in acid. The amount of free amino groups was analysed by IR. The molecular weight was determined by viscosimetry. Starch or dextran were oxidised with periodic acid to generate aldehyde groups, which were quantified by titration. l-Dopa was conjugated to oxidised dextran or starch in analogy to the gluing mechanism of mussels. Biomechanical studies revealed that the new glue is superior to fibrin glue, but has less adhesive strength than cyanoacrylates. In vitro cell testing demonstrated excellent biocompatibility, rendering this glue a potential candidate for clinical use.

  12. Assessing the potential of colony morphology for dissecting the CFU-F population from human bone marrow stromal cells.

    PubMed

    Gothard, D; Dawson, J I; Oreffo, R O C

    2013-05-01

    Mesenchymal stem cells (MSCs) provide an ideal cell source for bone tissue engineering strategies. However, bone marrow stromal cell (BMSC) populations that contain MSCs are highly heterogeneous expressing a wide variety of proliferative and differentiation potentials. Current MSC isolation methods employing magnetic-activated and fluorescent-activated cell sorting can be expensive and time consuming and, in the absence of specific MSC markers, fail to generate homogeneous populations. We have investigated the potential of various colony morphology descriptors to provide correlations with cell growth potential. Density-independent colony forming unit-fibroblastic (CFU-F) capacity is a MSC prerequisite and resultant colonies display an array of shapes and sizes that might be representative of cell function. Parent colonies were initially categorised according to their diameter and cell density and grouped before passage for the subsequent assessment of progeny colonies. Whereas significant morphological differences between distinct parent populations indicated a correlation with immunophenotype, enhanced CFU-F capacity was not observed when individual colonies were isolated according to these morphological parameters. Colony circularity, an alternative morphological measure, displayed a strong correlation with subsequent cell growth potential. The current study indicates the potential of morphological descriptors for predicting cell growth rate and suggests new directions for research into dissection of human BMSC CFU-F populations.

  13. [The application progress of human urine derived stem cells in bone tissue engineering].

    PubMed

    Gao, Peng; Jiang, Dapeng; Li, Zhaozhu

    2016-04-01

    The research of bone tissue engineering bases on three basic directions of seed cells, scaffold materials and growth information. Stem cells have been widely studied as seed cells. Human urine-derived stem cell (hUSC) is extracted from urine and described to be adhesion growth, cloning, expression of the majority of mesenchymal stem cell markers and peripheral cell markers, multi-potential and no tumor but stable karyotype with passaging many times. Some researches proposed that hUSC might be a new source of seed cells in tissue engineering because of their invasive and convenient obtention, stable culture and multiple differentiation potential.

  14. MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs

    PubMed Central

    Zhao, Qingguo; Gregory, Carl A.; Lee, Ryang Hwa; Reger, Roxanne L.; Qin, Lizheng; Hai, Bo; Park, Min Sung; Yoon, Nara; Clough, Bret; McNeill, Eoin; Prockop, Darwin J.; Liu, Fei

    2015-01-01

    Mesenchymal stem or stromal cells (MSCs) have many potential therapeutic applications including therapies for cancers and tissue damages caused by cancers or radical cancer treatments. However, tissue-derived MSCs such as bone marrow MSCs (BM-MSCs) may promote cancer progression and have considerable donor variations and limited expandability. These issues hinder the potential applications of MSCs, especially those in cancer patients. To circumvent these issues, we derived MSCs from transgene-free human induced pluripotent stem cells (iPSCs) efficiently with a modified protocol that eliminated the need of flow cytometric sorting. Our iPSC-derived MSCs were readily expandable, but still underwent senescence after prolonged culture and did not form teratomas. These iPSC-derived MSCs homed to cancers with efficiencies similar to BM-MSCs but were much less prone than BM-MSCs to promote the epithelial–mesenchymal transition, invasion, stemness, and growth of cancer cells. The observations were probably explained by the much lower expression of receptors for interleukin-1 and TGFβ, downstream protumor factors, and hyaluronan and its cofactor TSG6, which all contribute to the protumor effects of BM-MSCs. The data suggest that iPSC-derived MSCs prepared with the modified protocol are a safer and better alternative to BM-MSCs for therapeutic applications in cancer patients. The protocol is scalable and can be used to prepare the large number of cells required for “off-the-shelf” therapies and bioengineering applications. PMID:25548183

  15. Physicochemical Properties and Applications of Poly(lactic-co-glycolic acid) for Use in Bone Regeneration

    PubMed Central

    Félix Lanao, Rosa P.; Jonker, Anika M.; Wolke, Joop G.C.; Jansen, John A.; van Hest, Jan C.M.

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most often used synthetic polymer within the field of bone regeneration owing to its biocompatibility and biodegradability. As a consequence, a large number of medical devices comprising PLGA have been approved for clinical use in humans by the American Food and Drug Administration. As compared with the homopolymers of lactic acid poly(lactic acid) and poly(glycolic acid), the co-polymer PLGA is much more versatile with regard to the control over degradation rate. As a material for bone regeneration, the use of PLGA has been extensively studied for application and is included as either scaffolds, coatings, fibers, or micro- and nanospheres to meet various clinical requirements. PMID:23350707

  16. Physical and mechanical properties evaluation of Acropora palmata coralline species for bone substitution applications.

    PubMed

    Alvarez, K; Camero, S; Alarcón, M E; Rivas, A; González, G

    2002-05-01

    The search for ideal materials for bone substitution has been a challenge for many decades. Numerous natural and synthetic materials have been studied. For this application, exoskeletons of coral have been considered a good alternative given its tendency to resorption, biocompatibility and similarity to the mineral bone phase. Very few studies of these materials consider a detailed analysis of the structure-property relationship. The purpose of this work was to carry out the microstructural characterization of a coralline species named Acropora palmata and the determination of the mechanical and physico-chemical properties. Measurements of hardness, compressive strength, bulk density and apparent porosity were performed. From these results it was determined that this marine coral species could be an alternative xenograft due to its mechanical properties and osteoconductive nature.

  17. Potential application of Raman spectroscopy for determining burial duration of skeletal remains.

    PubMed

    McLaughlin, Gregory; Lednev, Igor K

    2011-11-01

    Raman spectroscopy was used to study trends in chemical composition of bones in a burial environment. A turkey bone was sectioned and buried for short intervals between 12 and 62 days. Buried sections were analyzed using Raman microspectroscopy with 785 nm excitation. The results indicate that chemical changes in bone due to soil bacteria are time-dependent. Spectroscopic trends within buried bone segments were correlated to burial duration. A preliminary model was constructed using peak integration of Raman bands. Data collected within buried bone segments fit very well in this model. The model constructed is sensitive to changes in bone composition in a scale of days. This study illustrates the great potential of Raman spectroscopy as a non-destructive method for estimating the burial duration of bone for forensic purposes.

  18. Evaluation of In Vivo Osteogenic Potential of Bone Morphogenetic Protein 2-Overexpressing Human Periodontal Ligament Stem Cells Combined with Biphasic Calcium Phosphate Block Scaffolds in a Critical-Size Bone Defect Model.

    PubMed

    Yi, TacGhee; Jun, Choong-Man; Kim, Su Jin; Yun, Jeong-Ho

    2016-03-01

    Human periodontal ligament stem cells (hPDLSCs) are considered potential cellular carriers for gene delivery in the field of tissue regeneration. This study tested the osseoregenerative potential of hPDLSCs transduced with replication-deficient recombinant adenovirus (rAd) containing the gene encoding bone morphogenetic protein-2 (BMP2; hPDLSCs/rAd-BMP2) in both in vivo and in vitro osteogenic environments. After the optimal condition for rAd-mediated transduction was determined, hPDLSCs were transduced to express BMP2. In vivo bone formation was evaluated in a critical-size rat calvarial bone defect model that more closely mimics the harsher in vivo milieu for bone regeneration than subcutaneous transplantation model. As support materials for bone regeneration, block-type biphasic calcium phosphate (BCP) scaffolds were combined with hPDLSCs and/or BMP2 and transplanted into critical-size bone defects in rats. Experimental groups were as follows: BCP scaffold control (group 1 [Gr1]), scaffold containing recombinant human BMP2 (rhBMP2; group 2 [Gr2]), scaffold loaded with normal hPDLSCs (group 3 [Gr3]), scaffold combined with both normal hPDLSCs and rhBMP2 (group 4 [Gr4]), and scaffold loaded with hPDLSCs transduced with rAd-BMP2 (hPDLSCs/rAd-BMP2; group 5 [Gr5]). Our data showed that new bone formation was highest in Gr2. Less mineralization was observed in Gr3, Gr4, and Gr5 in which hPDLSCs were transplanted. In vitro transwell assay demonstrated that hPDLSCs exert an inhibitory activity on BMP2-induced osteogenic differentiation. Our findings suggest that the in vivo bone regenerative potential of BMP2-overexpressing hPDLSCs could be compromised in a critical-size rat calvarial bone defect model. Thus, further investigations are required to elucidate the underlying mechanisms and to develop efficient techniques for improved tissue regeneration.

  19. Advances in the design of macroporous polymer scaffolds for potential applications in dentistry

    PubMed Central

    Braschler, Thomas M.; Renaud, Philippe

    2013-01-01

    A paradigm shift is taking place in medicine and dentistry from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous three-dimensional (3D) material hydrogels integrated with cells and bioactive factors to regenerate tissues such as dental bone and other oral tissues. Hydrogels have been established as a biomaterial of choice for many years, as they offer diverse properties that make them ideal in regenerative medicine, including dental applications. Being highly biocompatible and similar to native extracellular matrix, hydrogels have emerged as ideal candidates in the design of 3D scaffolds for tissue regeneration and drug delivery applications. However, precise control over hydrogel properties, such as porosity, pore size, and pore interconnectivity, remains a challenge. Traditional techniques for creating conventional crosslinked polymers have demonstrated limited success in the formation of hydrogels with large pore size, thus limiting cellular infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the case of bone) of tissue-engineered constructs. Emerging technologies have demonstrated the ability to control microarchitectural features in hydrogels such as the creation of large pore size, porosity, and pore interconnectivity, thus allowing the creation of engineered hydrogel scaffolds with a structure and function closely mimicking native tissues. In this review, we explore the various technologies available for the preparation of macroporous scaffolds and their potential applications. PMID:24455437

  20. Tantalum trabecular metal - addition of human skeletal cells to enhance bone implant interface strength and clinical application.

    PubMed

    Smith, J O; Sengers, B G; Aarvold, A; Tayton, E R; Dunlop, D G; Oreffo, R O C

    2014-04-01

    The osteo-regenerative properties of allograft have recently been enhanced by addition of autogenous human bone marrow stromal cells (HBMSCs). Limitations in the use of allograft have prompted the investigation of tantalum trabecular metal (TTM) as a potential alternative. TTM is already in widespread orthopaedic use, although in applications where there is poor initial stability, or when TTM is used in conjunction with bone grafting, initial implant loading may need to be limited. The aim of this study was to evaluate the osteo-regenerative potential of TTM with HBMSCs, in direct comparison to human allograft and autograft. HBMSCs were cultured on blocks of TTM, allograft or autograft in basal and osteogenic media. Molecular profiling, confocal and scanning electron microscopy (SEM) and biochemical assays were used to characterize cell adherence, proliferation and phenotype. Mechanical testing was used to define the tensile characteristics of the constructs. HBMSCs displayed adherence and proliferation throughout TTM, evidenced by immunocytochemistry and SEM, with significant cellular ingrowth and matrix production through TTM. In contrast to cells cultured with allograft, cell proliferation assays showed significantly higher activity with TTM (p < 0.001), although molecular profiling confirmed no significant difference in expression of osteogenic genes. In contrast to acellular constructs, mechanical testing of cell-TTM constructs showed enhanced tensile characteristics, which compared favourably to cell-allograft constructs. These studies demonstrated the ability of TTM to support HBMSC growth and osteogenic differentiation comparable to allograft. Thus, TTM represents an alternative to allograft for osteo-regenerative strategies, extending its clinical applications as a substitute for allograft.

  1. Potential Association of Posttraumatic Stress Disorder and Decreased Bone Mineral Density in Repatriated Prisoners of War

    DTIC Science & Technology

    2011-03-01

    the US. All rights reserved. MILITARY MEDICINE, 176, 3:270, 2011 270 MILITARY MEDICINE, Vol. 176, March 2011 INTRODUCTION Osteoporosis is defi ned...and susceptibility to fracture. 1 Male osteoporosis is a less well- recognized and studied condition compared to osteoporosis in women. It is known...that approximately 1–2 million men in the United States have osteoporosis and another 8–13 million have osteopenia or decreased bone mass. 2 One-third

  2. Actinide(IV) Deposits on Bone: Potential Role of the Osteopontin-Thorium Complex.

    PubMed

    Creff, Gaëlle; Safi, Samir; Roques, Jérôme; Michel, Hervé; Jeanson, Aurélie; Solari, Pier-Lorenzo; Basset, Christian; Simoni, Eric; Vidaud, Claude; Den Auwer, Christophe

    2016-01-04

    In case of a nuclear event, contamination (broad or limited) of the population or of specific workers might occur. In such a senario, the fate of actinide contaminants may be of first concern, in particular with regard to human target organs like the skeleton. To improve our understanding of the toxicological processes that might take place, a mechanistic approach is necessary. For instance, ∼50% of Pu(IV) is known from biokinetic data to accumulate in bone, but the underlining mechanisms are almost unknown. In this context, and to obtain a better description of the toxicological mechanisms associated with actinides(IV), we have undertaken the investigation, on a molecular scale, of the interaction of thorium(IV) with osteopontin (OPN) a hyperphosphorylated protein involved in bone turnover. Thorium is taken here as a simple model for actinide(IV) chemistry. In addition, we have selected a phosphorylated hexapeptide (His-pSer-Asp-Glu-pSer-Asp-Glu-Val) that is representative of the peptidic sequence involved in the bone interaction. For both the protein and the biomimetic peptide, we have determined the local environment of Th(IV) within the bioactinidic complex, combining isothermal titration calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, theoretical calculations with density functional theory, and extended X-ray absorption fine structure spectroscopy at the Th LIII edge. The results demonstrate a predominance of interaction of metal with the phosphate groups and confirmed the previous physiological studies that have highlighted a high affinity of Th(IV) for the bone matrix. Data are further compared with those of the uranyl case, representing the actinyl(V) and actinyl(VI) species. Last, our approach shows the importance of developing simplified systems [Th(IV)-peptide] that can serve as models for more biologically relevant systems.

  3. Microbial surfactants and their potential applications: an overview.

    PubMed

    Mukherjee, Ashis K; Das, Kishore

    2010-01-01

    Biosurfactant or microbial surfactants produced by microbes are structurally diverse and heterogeneous groups of surface-active amphipathic molecules. They are capable of reducing surface and interfacial tension and have a wide range of industrial and environmental applications. The present chapter reviews the biochemical properties of different classes of microbial surfactants and their potential application in different industrial sectors.

  4. Past applications and future potential of variable stability research helicopters

    NASA Technical Reports Server (NTRS)

    Hindson, W. S.

    1982-01-01

    The historical development of variable-stability research helicopters and some of their previous applications are presented as a guide for assessing their future potential. The features of three general-purpose rotary-wing flight research aircraft that provide complementary capabilities are described briefly, and a number of future applications are proposed.

  5. Potential applications of computational fluid dynamics to biofluid analysis

    NASA Technical Reports Server (NTRS)

    Kwak, D.; Chang, J. L. C.; Rogers, S. E.; Rosenfeld, M.; Kwak, D.

    1988-01-01

    Computational fluid dynamics was developed to the stage where it has become an indispensable part of aerospace research and design. In view of advances made in aerospace applications, the computational approach can be used for biofluid mechanics research. Several flow simulation methods developed for aerospace problems are briefly discussed for potential applications to biofluids, especially to blood flow analysis.

  6. A comparative study of zwitterionic ligands-mediated mineralization and the potential of mineralized zwitterionic matrices for bone tissue engineering

    PubMed Central

    Liu, Pingsheng; Emmons, Erin

    2014-01-01

    Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapaptite (HA)-mineralization of photo-crosslinked polymethacrylatehydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using the crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralizationthan the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24-h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering. PMID:25558374

  7. Theory of the induction of bone sarcoma by bone-seeking alpha emitters and its application to risk assessment

    SciTech Connect

    Petojan, I.M.

    1992-06-01

    This work discusses the theory of bone sarcoma induction by bone seeking alpha emitters, which is based strictly on biological considerations relative to the mechanism of radiation-induced carcinogenesis, identification of cells at risk and their location in bone, bone tissue renewal processes and bone cell kinetics with or without radiation exposure. The model is consistent with the data on bone sarcoma incidence human with incorporated long-lived isotopes Ra-226 + Ra-228. Extrapolation of these data to a low intake region of the basis of the developed theoretical approach suggests that the linear ICRP-UNSCEAR model overestimates carciogenic risk at low doses, possibly by a factor of 2-4. The model suggests a linear response of target cells to the initiation effects of alpha irradiation. The non-linear (linear-quadratic) initial part of dose-response curve for osteosarcoma induction is explained quantitatively by a model based on a promoter effect of regenerative hyperplasia resulting from invitation effects of alpha radiation. The maximum overestimation inherent to the model of the low-level risk due to the the dose-dependent promotion factor is estimated using bo{sup +1}/bo, where bo is a model parameter which is proportional to the normal division rate of osteogenic cells in vivo and which can be estimated within the framework of the model. The model provides confirming evidence that, for radiation protection purposes, endosteal cells may be considered the only group of cells at risk of sarcoma induction by low doses of bone-seeking alpha emitters, whereas the role of marrow stromal (osteogenic) cells as target cells is much more significant with increasing intakes, and can become dominating if intake is high enough.

  8. Distance between implants has a potential impact of crestal bone resorption

    PubMed Central

    Danza, Matteo; Zollino, Ilaria; Avantaggiato, Anna; Lucchese, Alessandra; Carinci, Francesco

    2011-01-01

    Objectives Around dental implants exists a “biologic width” of few millimeters that have to be preserved in order to not have adverse effect on soft and hard tissues around implant. Because the minimum distance between adjacent implants has not been determined yet, we therefore, decided to perform a retrospective study on a series of spiral family implants (SFIs) to verify the minimum inter-implants’ distance that has an impact on crestal bone resorption. Materials and Methods Fifty-nine implants were investigated with a mean follow-up of 14 months. Implant diameter was 3.75, 4.2, 5 and 6 mm in 11 (18.6%), 29 (49.2%), 17 (28.8%) and 2 (3.4%) SFIs. Implant length was shorter than 13 mm, equal to 13 mm and 16 mm in 23 (39%), 23 (39%) and 13 (22%) SFIs. Implants were inserted to replace 13 incisors (22%), 7 cuspids (11.9%), 30 premolars (50.8%) and 9 molars (15.3%). Twenty-seven fixtures were inserted in post-extractive sockets and the remaining 32 in healed bone; 36 (61%) were immediately loaded. In addition to the above mentioned implant-related factors, several host- and surgery-factors were investigated. Independent samples T-test, univariate and multivariate analysis were used to detect those variables associated with the clinical outcome. Results Data were evaluated with a two steps statistical analysis (i.e. univariate and multivariate) after having grouped implants in two series: those with an implant-implant distance less of 1.8 mm and those with an implant-implants distance greater than 1.8 mm. In univariate analysis, post-extractive implants and number of prosthetic units were statistically significant. In multivariate analysis, only post-extractive implants have a significant adverse effect on crestal bone resorption. Conclusions Adjacent implants inserted with a distance lower and higher than 1.8 mm have difference in crestal bone resorption but this difference is not statistically significant in a short period follow up. This could due to

  9. Increasing dietary phosphorus intake from food additives: potential for negative impact on bone health.

    PubMed

    Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

    2014-01-01

    It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health

  10. Donor-Matched Comparison of Chondrogenic Potential of Equine Bone Marrow- and Synovial Fluid-Derived Mesenchymal Stem Cells: Implications for Cartilage Tissue Regeneration

    PubMed Central

    Zayed, Mohammed; Caniglia, Christopher; Misk, Nabil; Dhar, Madhu S.

    2017-01-01

    Mesenchymal stem cells (MSCs) have been demonstrated to be useful for cartilage tissue regeneration. Bone marrow (BM) and synovial fluid (SF) are promising sources for MSCs to be used in cartilage regeneration. In order to improve the clinical outcomes, it is recommended that prior to clinical use, the cellular properties and, specifically, their chondrogenic potential must be investigated. The purpose of this study is to compare and better understand the in vitro chondrogenic potential of equine bone marrow-derived mesenchymal stem cells (BMMSCs) and synovial fluid-derived mesenchymal stem cells (SFMSCs) populated from the same equine donor. BM- and SF-derived MSCs cultures were generated from five equine donors, and the MSCs were evaluated in vitro for their morphology, proliferation, trilineage differentiation, and immunophenotyping. Differences in their chondrogenic potentials were further evaluated quantitatively using glycosaminoglycan (GAG) content and via immunofluorescence of chondrogenic differentiation protein markers, SRY-type HMG box9, Aggrecan, and collagen II. The BMMSCs and SFMSCs were similar in cellular morphology, viability, and immunophenotype, but, varied in their chondrogenic potential, and expression of the key chondrogenic proteins. The SFMSCs exhibited a significant increase in GAG content compared to the BMMSCs (P < 0.0001) in three donors, suggesting increased levels of chondrogenesis. The expression of the key chondrogenic proteins correlated positively with the GAG content, suggesting that the differentiation process is dependent on the expression of the target proteins in these three donors. Our findings suggest that even though SFMSCs were hypothesized to be more chondrogenic relative to BMMSCs, there was considerable donor-to-donor variation in the primary cultures of MSCs which can significantly affect their downstream application. PMID:28149840

  11. Enrichment of thermosensitive chitosan hydrogels with glycerol and alkaline phosphatase for bone tissue engineering applications.

    PubMed

    Douglas, Timothy E L; Krok-Borkowicz, Małgorzata; Macuda, Aleksandra; Pietryga, Krzysztof; Pamuła, Elżbieta

    2016-01-01

    Thermosensitive injectable chitosan hydrogels can be formed by neutralization of acidic chitosan solutions with sodium betaglycerophosphate (Na-β-GP) coupled with increasing temperature to body temperature. Such hydrogels have been considered for applications in bone regeneration. In this study, chitosan hydrogels were enriched with glycerol and the enzyme alkaline phosphatase (ALP) with a view to improving their suitability as materials for bone tissue engineering. Mineral formation was confirmed by infrared spectroscopy (FTIR) and increases in the mass fraction of the hydrogel not consisting of water. Incorporation of ALP in hydrogels followed by incubation in a solution containing calcium ions and glycerophosphate, a substrate for ALP, led to formation of calcium phosphate within the hydrogel. MG-63 osteoblast-like cells were cultivated in eluates from hydrogels containing ALP and without ALP at different dilutions and directly on the hydrogel samples. Hydrogels containing ALP exhibited superior cytocompatibility to ALP-free hydrogels. These results pave the way for the use of glycerol- and ALP-enriched hydrogels in bone regeneration.

  12. Development of thermosensitive hydrogels of chitosan, sodium and magnesium glycerophosphate for bone regeneration applications.

    PubMed

    Lisková, Jana; Bačaková, Lucie; Skwarczyńska, Agata L; Musial, Olga; Bliznuk, Vitaliy; De Schamphelaere, Karel; Modrzejewska, Zofia; Douglas, Timothy E L

    2015-04-09

    Thermosensitive injectable hydrogels based on chitosan neutralized with sodium beta-glycerophosphate (Na-β-GP) have been studied as biomaterials for drug delivery and tissue regeneration. Magnesium (Mg) has been reported to stimulate adhesion and proliferation of bone forming cells. With the aim of improving the suitability of the aforementioned chitosan hydrogels as materials for bone regeneration, Mg was incorporated by partial substitution of Na-β-GP with magnesium glycerophosphate (Mg-GP). Chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were also loaded with the enzyme alkaline phosphatase (ALP) which induces hydrogel mineralization. Hydrogels were characterized physicochemically with respect to mineralizability and gelation kinetics, and biologically with respect to cytocompatibility and cell adhesion. Substitution of Na-β-GP with Mg-GP did not negatively influence mineralizability. Cell biological testing showed that both chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were cytocompatible towards MG63 osteoblast-like cells. Hence, chitosan/Na-β-GP/Mg-GP hydrogels can be used as an alternative to chitosan/Na-β-GP hydrogels for bone regeneration applications. However the incorporation of Mg in the hydrogels during hydrogel formation did not bring any appreciable physicochemical or biological benefit.

  13. Development of multi-substituted hydroxyapatite nanopowders as biomedical materials for bone tissue engineering applications.

    PubMed

    Baba Ismail, Yanny M; Wimpenny, Ian; Bretcanu, Oana; Dalgarno, Kenneth; El Haj, Alicia J

    2017-02-15

    Ionic substitutions have been proposed as a tool to control the functional behavior of synthetic hydroxyapatite (HA), particularly for Bone Tissue Engineering (BTE) applications. The effect of simultaneous substitution of different levels of carbonate (CO3 ) and silicon (Si) ions in the HA lattice was investigated. Furthermore, human bone marrow-derived mesenchymal stem cells (hMSCs) were cultured on multi-substituted HA (SiCHA) to determine if biomimetic chemical compositions were osteoconductive. Of the four different compositions investigates, SiCHA-1 (0.58wt% Si) and SiCHA-2 (0.45wt% Si) showed missing bands for CO3 and Si using FTIR analysis, indicating competition for occupation of the phosphate site in the HA lattice. 500°C was considered the most favourable calcination temperature as: (i) the powders produced possessed a similar amount of CO3 (2-8wt%) and Si (<1.0wt%) as present in native bone; and (ii) there was a minimal loss of CO3 and Si from the HA structure to the surroundings during calcination. Higher Si content in SiCHA-1 led to lower cell viability and at most hindered proliferation, but no toxicity effect occurred. While, lower Si content in SiCHA-2 showed the highest ALP/DNA ratio after 21 days culture with hMSCs, indicating that the powder may stimulate osteogenic behaviour to a greater extent than other powders. This article is protected by copyright. All rights reserved.

  14. Development of Thermosensitive Hydrogels of Chitosan, Sodium and Magnesium Glycerophosphate for Bone Regeneration Applications

    PubMed Central

    Lisková, Jana; Bačaková, Lucie; Skwarczyńska, Agata L.; Musial, Olga; Bliznuk, Vitaliy; De Schamphelaere, Karel; Modrzejewska, Zofia; Douglas, Timothy E.L.

    2015-01-01

    Thermosensitive injectable hydrogels based on chitosan neutralized with sodium beta-glycerophosphate (Na-β-GP) have been studied as biomaterials for drug delivery and tissue regeneration. Magnesium (Mg) has been reported to stimulate adhesion and proliferation of bone forming cells. With the aim of improving the suitability of the aforementioned chitosan hydrogels as materials for bone regeneration, Mg was incorporated by partial substitution of Na-β-GP with magnesium glycerophosphate (Mg-GP). Chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were also loaded with the enzyme alkaline phosphatase (ALP) which induces hydrogel mineralization. Hydrogels were characterized physicochemically with respect to mineralizability and gelation kinetics, and biologically with respect to cytocompatibility and cell adhesion. Substitution of Na-β-GP with Mg-GP did not negatively influence mineralizability. Cell biological testing showed that both chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were cytocompatible towards MG63 osteoblast-like cells. Hence, chitosan/Na-β-GP/Mg-GP hydrogels can be used as an alternative to chitosan/Na-β-GP hydrogels for bone regeneration applications. However the incorporation of Mg in the hydrogels during hydrogel formation did not bring any appreciable physicochemical or biological benefit. PMID:25859630

  15. Preparation and biocompatibility evaluation of bioactive glass-forsterite nanocomposite powder for oral bone defects treatment applications.

    PubMed

    Saqaei, Mahboobe; Fathi, Mohammadhossein; Edris, Hossein; Mortazavi, Vajihesadat

    2015-11-01

    Bone defects which emerge around dental implants are often seen when implants are placed in areas with insufficient alveolar bone, in extraction sockets, or around failing implants. Bone regeneration in above-mentioned defects using of bone grafts or bone substitutes may cure the long-term prognoses of dental implants. Biocompatibility, bioactivity and osteogenic properties are key factors affecting the applications of a bone substitute. This study was aimed at preparation, characterization, biocompatibility and bioactivity evaluation of the bioactive glass-forsterite nanocomposite powder as a desired candidate for oral bone defect treatments. Nanocomposite powders containing 58S bioactive glass and different amounts of forsterite nanopowder were synthesized in situ by sol-gel technique. Characterization of the prepared nanocomposite powders and their cytotoxicity assessment was performed via MTT test. Bioactivity assessment was done by immersing the prepared powder in the simulated body fluid (SBF). Results showed that nanocomposite powders containing forsterite with crystallite size of 20-50nm were successfully fabricated by calcination at 600°C. The prepared bioactive glass-forsterite nanocomposite powders revealed high in vitro biocompatibility; besides, the nanocomposite containing 20wt.% forsterite showed a substantial increase in the cell viability compared with control groups. During immersion in SBF, the formation of apatite layer confirmed the bioactivity of bioactive glass-forsterite nanocomposite powders. According to the results, the fabricated nanocomposite powders can be introduced as a promising candidate for oral bone imperfection treatments and hard tissue mend.

  16. Applications of the direct photon absorption technique for measuring bone mineral content in vivo. Determination of body composition in vivo

    NASA Technical Reports Server (NTRS)

    Cameron, J. R.

    1972-01-01

    The bone mineral content, BMC, determined by monoenergetic photon absorption technique, of 29 different locations on the long bones and vertebral columns of 24 skeletons was measured. Compressive tests were made on bone from these locations in which the maximum load and maximum stress were measured. Also the ultimate strain, modulus of elasticity and energy absorbed to failure were determined for compact bone from the femoral diaphysis and cancellous bone from the eighth through eleventh thoracic vertebrae. Correlations and predictive relationships between these parameters were examined to investigate the applicability of using the BMC at sites normally measured in vivo, i.e. radius and ulna in estimating the BMC and/or strength of the spine or femoral neck. It was found that the BMC at sites on the same bone were highly correlated r = 0.95 or better; the BMC at sites on different bones were also highly interrelated, r = 0.85. The BMC at various sites on the long bones could be estimated to between 10 and 15 per cent from the BMC of sites on the radius or ulna.

  17. Origin matters: differences in embryonic tissue origin and Wnt signaling determine the osteogenic potential and healing capacity of frontal and parietal calvarial bones.

    PubMed

    Quarto, Natalina; Wan, Derrick C; Kwan, Matt D; Panetta, Nicholas J; Li, Shuli; Longaker, Michael T

    2010-07-01

    Calvarial bones arise from two embryonic tissues, namely, the neural crest and the mesoderm. In this study we have addressed the important question of whether disparate embryonic tissue origins impart variable osteogenic potential and regenerative capacity to calvarial bones, as well as what the underlying molecular mechanism(s). Thus, by performing in vitro and in vivo studies, we have investigated whether differences exist between neural crest-derived frontal and paraxial mesodermal-derived parietal bone. Of interest, our data indicate that calvarial bone osteoblasts of neural crest origin have superior potential for osteogenic differentiation. Furthermore, neural crest-derived frontal bone displays a superior capacity to undergo osseous healing compared with calvarial bone of paraxial mesoderm origin. Our study identified both in vitro and in vivo enhanced endogenous canonical Wnt signaling in frontal bone compared with parietal bone. In addition, we demonstrate that constitutive activation of canonical Wnt signaling in paraxial mesodermal-derived parietal osteoblasts mimics the osteogenic potential of frontal osteoblasts, whereas knockdown of canonical Wnt signaling dramatically impairs the greater osteogenic potential of neural crest-derived frontal osteoblasts. Moreover, fibroblast growth factor 2 (FGF-2) treatment induces phosphorylation of GSK-3beta and increases the nuclear levels of beta-catenin in osteoblasts, suggesting that enhanced activation of Wnt signaling might be mediated by FGF. Taken together, our data provide compelling evidence that indeed embryonic tissue origin makes a difference and that active canonical Wnt signaling plays a major role in contributing to the superior intrinsic osteogenic potential and tissue regeneration observed in neural crest-derived frontal bone.

  18. Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges.

    PubMed

    Mueller, S M; Glowacki, J

    2001-01-01

    Studies with human and animal culture systems indicate that a sub-population of bone marrow stromal cells has the potential to differentiate into osteoblasts. There are conflicting reports on the effects of age on human marrow-derived osteogenic cells. In this study, we used a three dimensional (3D) culture system and quantitative RT-PCR methods to test the hypothesis that the osteogenic potential of human bone marrow stromal cells decreases with age. Marrow was obtained from 39 men aged 37 to 86 years, during the course of total hip arthroplasty. Low-density mononuclear cells were seeded onto 3D collagen sponges and cultured for 3 weeks. Histological sections of sponges were stained for alkaline phosphatase activity and were scored as positive or negative. In the group < or = 50 years, 7 of 11 samples (63%) were positive, whereas only 5 of 19 (26%) of the samples in the group > or = 60 years were positive (p = 0.0504). As revealed by RT-PCR, there was no expression of alkaline phosphatase or collagen type I mRNA before culture, however there were strong signals after 3 weeks, an indication of osteoblast differentiation in vitro. We performed a quantitative, competitive RT-PCR assay with 8 samples (age range 38-80) and showed that the group < or = 50 years had 3-fold more mRNA for alkaline phosphatase than the group > or = 60 years (p = 0.021). There was a significant decrease with age (r = - 0.78, p = 0.028). These molecular and histoenzymatic data indicate that the osteogenic potential of human bone marrow cells decreases with age.

  19. Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential

    PubMed Central

    Chen, Yijia; Xu, Xiaomei; Tan, Zhen; Ye, Cui; Chen, Yangxi

    2012-01-01

    Introduction Aging people's bone regeneration potential is always impaired. Bone marrow stromal cells (MSCs) contain progenitors of osteoblasts. Donor age may affect MSCs’ proliferation and differentiation potential, but the genomic base is still unknown. Due to recent research's indication that a core circadian component, brain and muscle ARNT-like 1 protein (BMAL1), has a role in premature aging, we investigated the normal aging mechanism in mice with their MSCs and Bmal1 gene/protein level. Material and methods 1, 6 and 16 month old C57BL/6 mice were used and the bone marrow stromal cells were gained and cultured at early passage. Bmal1 gene and protein level were detected in these cells. Marrow stromal cells were also induced to differentiate to osteoblasts or adipocytes. Three groups of mice MSCs were compared on proliferation by flow cytometry, on cell senescence by SA-β-gal expression and after osteo-induction on osteogenic potential by the expression of osterix (Osx), alkaline phosphatase (ALP) and osteocalcin (OCN). Results Bmal1 gene and protein level as well as S-phase fraction of the cell cycle decreased in MSCs along with the aging process. At the same time, SA-β-gal+ levels increased, especially in the aged mice MSCs. When induced to be osteogenic, Osx gene expression and ALP activity declined in the mid-age and aged mice MSCs, while OCN protein secretion deteriorated in the aged mice MSCs. Conclusions These findings demonstrate that mouse MSCs changed with their proliferation and osteo-differentiation abilities at different aging stages, and that Bmal1 is related to the normal aging process in MSCs. PMID:22457671

  20. Clinical Applications of S53P4 Bioactive Glass in Bone Healing and Osteomyelitic Treatment: A Literature Review.

    PubMed

    van Gestel, N A P; Geurts, J; Hulsen, D J W; van Rietbergen, B; Hofmann, S; Arts, J J

    2015-01-01

    Nowadays, S53P4 bioactive glass is indicated as a bone graft substitute in various clinical applications. This review provides an overview of the current published clinical results on indications such as craniofacial procedures, grafting of benign bone tumour defects, instrumental spondylodesis, and the treatment of osteomyelitis. Given the reported results that are based on examinations, such as clinical examinations by the surgeons, radiographs, CT, and MRI images, S53P4 bioactive glass may be beneficial in the various reported applications. Especially in craniofacial reconstructions like mastoid obliteration and orbital floor reconstructions, in grafting bone tumour defects, and in the treatment of osteomyelitis very promising results are obtained. Randomized clinical trials need to be performed in order to determine whether bioactive glass would be able to replace the current golden standard of autologous bone usage or with the use of antibiotic containing PMMA beads (in the case of osteomyelitis).

  1. Clinical Applications of S53P4 Bioactive Glass in Bone Healing and Osteomyelitic Treatment: A Literature Review

    PubMed Central

    van Gestel, N. A. P.; Geurts, J.; Hulsen, D. J. W.; van Rietbergen, B.; Hofmann, S.; Arts, J. J.

    2015-01-01

    Nowadays, S53P4 bioactive glass is indicated as a bone graft substitute in various clinical applications. This review provides an overview of the current published clinical results on indications such as craniofacial procedures, grafting of benign bone tumour defects, instrumental spondylodesis, and the treatment of osteomyelitis. Given the reported results that are based on examinations, such as clinical examinations by the surgeons, radiographs, CT, and MRI images, S53P4 bioactive glass may be beneficial in the various reported applications. Especially in craniofacial reconstructions like mastoid obliteration and orbital floor reconstructions, in grafting bone tumour defects, and in the treatment of osteomyelitis very promising results are obtained. Randomized clinical trials need to be performed in order to determine whether bioactive glass would be able to replace the current golden standard of autologous bone usage or with the use of antibiotic containing PMMA beads (in the case of osteomyelitis). PMID:26504821

  2. Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration

    PubMed Central

    O'Valle, Francisco; Lanis, Alejandro; Dohan Ehrenfest, David M.; Wang, Hom-Lay; Galindo-Moreno, Pablo

    2015-01-01

    Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled) and case reports/series describing the clinical use of mesenchymal stem cells (MSCs) in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes. PMID:26064899

  3. Concise reviews: Characteristics and potential applications of human dental tissue-derived mesenchymal stem cells.

    PubMed

    Liu, Junjun; Yu, Fang; Sun, Yao; Jiang, Beizhan; Zhang, Wenjun; Yang, Jianhua; Xu, Guo-Tong; Liang, Aibin; Liu, Shangfeng

    2015-03-01

    Recently, numerous types of human dental tissue-derived mesenchymal stem cells (MSCs) have been isolated and characterized, including dental pulp stem cells, stem cells from exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle progenitor cells, alveolar bone-derived MSCs, stem cells from apical papilla, tooth germ progenitor cells, and gingival MSCs. All these MSC-like cells exhibit self-renewal, multilineage differentiation potential, and immunomodulatory properties. Several studies have demonstrated the potential advantages of dental stem cell-based approaches for regenerative treatments and immunotherapies. This review outlines the properties of various dental MSC-like populations and the progress toward their use in regenerative therapy. Several dental stem cell banks worldwide are also introduced, with a view toward future clinical application.

  4. Locust bean gum: Exploring its potential for biopharmaceutical applications.

    PubMed

    Dionísio, Marita; Grenha, Ana

    2012-07-01

    Polysaccharides have been finding, in the last decades, very interesting and useful applications in the biomedical and, specifically, in the biopharmaceutical field. Locust bean gum is a polysaccharide belonging to the group of galactomannans, being extracted from the seeds of the carob tree (Ceratonia siliqua). This polymer displays a number of appealing characteristics for biopharmaceutical applications, among which its high gelling capacity should be highlighted. In this review, we describe critical aspects of locust bean gum, contributing for its role in biopharmaceutical applications. Physicochemical properties, as well as strong and effective synergies with other biomaterials are described. The potential for in vivo biodegradation is explored and the specific biopharmaceutical applications are discussed.

  5. Beyond Osteogenesis: An in vitro Comparison of the Potentials of Six Bone Morphogenetic Proteins

    DTIC Science & Technology

    2013-10-01

    compared in terms of their ability to affect the release of stromal derived factor-1 ( SDF -1), vascular endothelial growth factor (VEGF), and basic...fibroblast growth factor (b-FGF) from human bone marrow stromal cells (hBMSCs). Gene expression of ALP, osteocalcin, SDF -1, VEGF, and b-FGF following...BMPs-6 and -9 produced the greatest osteogenic differentiation of C2C12 and hASCs as determined by ALP. The hBMSC secretion of SDF -1 was most

  6. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration.

    PubMed

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

  7. Evaluation of the potential of chitosan/β-1,3-glucan/hydroxyapatite material as a scaffold for living bone graft production in vitro by comparison of ADSC and BMDSC behaviour on its surface.

    PubMed

    Przekora, Agata; Vandrovcova, Marta; Travnickova, Martina; Pajorova, Julia; Molitor, Martin; Ginalska, Grazyna; Bacakova, Lucie

    2017-02-24

    The opinion regarding the origin of adult stem cells that should be used for living bone construct generation is strongly divided in the scientific community. In this study, the potential of chitosan/β-1,3-glucan/hydroxyapatite (chit/glu/HA) material as a scaffold for bone regeneration applications was evaluated by behaviour comparison of adult stem cells derived from both origins-adipose derived mesenchymal stem cell (ADSC) tissue and bone marrow derived mesenchymal stem cells (BMDSCs). In the case of ADSC isolation, low and high negative pressures were applied during a liposuction procedure in order to determine if negative pressure settings may have an impact on subsequent cell behaviour in vitro. The obtained results demonstrated that the chit/glu/HA material is a promising candidate to be used for living bone graft production in vitro as both ADSCs and BMDSCs revealed a satisfactory proliferation and differentiation ability on its surface. Nevertheless, BMDSCs would be a better choice of adult stem cells since they were better spread, more strongly attached and showed a more superior proliferation and differentiation ability than ADSCs when cultured on the chit/glu/HA scaffold. However, if BMDSCs cannot be isolated, ADSCs may be used for bone construct production but lipoaspirate should be collected under low negative pressure (-200 mm Hg), as high negative pressure (-700 mmHg) applied during liposuction surgery may retard subsequent ADSC proliferation and type I collagen production.

  8. Demineralized bone matrix as an osteoinductive biomaterial and in vitro predictors of its biological potential.

    PubMed

    Katz, Jordan M; Nataraj, Chandra; Jaw, Rebecca; Deigl, Elizabeth; Bursac, Predrag

    2009-04-01

    The osteoinductivity of demineralized bone matrix (DBM) varies from donor to donor as a result of varying levels of multiple growth factors, matrix integrity, and artifacts from material processing. Many in vitro assays are currently used for screening the osteoinductivity of DBM. The objectives of this study were to determine the correlation of specific growth factors and in vitro mitotic stimulation to in vivo ectopic bone formation capacity with a large number of DBM samples. Samples were assayed using ELISA methods for BMP-2/4 and TGF-beta1 (n = 304) and cell proliferation using SAOS-2 osteoblasts (n = 239). All samples were then implanted intramuscularly in the abdomen of nude rats. All in vitro assays showed significant variability for any particular level of ostoinductivity determined by in vivo model. A significant, but only very weak, positive correlation to in vivo results was found for TGF-beta1 (r(2) = 0.016), BMP 2/4 (r(2) = 0.065), and SAOS-2 cell proliferation (r(2) = 0.053). The results of this study amplify the notion that a multitude of factors and their relative interplay, rather than a single factor are likely to determine the potency of any particular lot of DBM.

  9. [Sawing and welding with ultrasonics. Experimental investigation to test the applicability of an apparatus for sawing and welding bone tissue with ultrasonics in orthopedics (author's transl)].

    PubMed

    Picht, U; Schumpe, G; Milachowski, K

    1977-02-01

    An experimental investigation of a procedure for sawing and welding of bone tissue with ultrasonics in the area of orthopedics was reported. The welding of bone with ultrasonic waves, bone meal and a plastic adhesive did not product satisfactory results in terms of stability and tissue reaction. The applicability of the ultrasonic saw is limited by the thickness of the bone on which the osteotomy is to be performed. We saw no advantages over against the oscillating saws which were available to us. In our opinion, an indication for the application of the ultrasonic apparatus could be the removal of inflammatory, tumerous or necrotic bone processes.

  10. Bone graft

    MedlinePlus

    Autograft - bone; Allograft - bone; Fracture - bone graft; Surgery - bone graft; Autologous bone graft ... Fuse joints to prevent movement Repair broken bones (fractures) that have bone loss Repair injured bone that ...

  11. Modeling and analysis of 3-D elongated shapes with applications to long bone morphometry

    SciTech Connect

    Burdin, V.; Roux, C.; Lefevre, C.; Stindel, E.

    1996-02-01

    This paper presents a geometric model to be used as a framework for the description and analysis of three-dimensional (3-D) elongated shapes. Elongated shapes can be decomposed into two different parts: a 3-D curve (the central axis) and a 3-D surface (the straight surface). The central axis is described in terms of curvature and torsion. A novel concept of torsion image is introduced which allows the user to study the torsion of some relevant 3-D structures such as the medulla of long bones, without computing the third derivative. The description of the straight surface is based on an ordered set of Fourier Descriptors (FD`s), each set representing a 2-D slice of the structure. These descriptors possess completeness, continuity, and stability properties, and some geometrical invariancies. A polar diagram is built which contains the anatomical information of the straight surface and can be used as a tool for the analysis and discrimination of 3-D structures. A technique for the reconstruction of the 3-D surface from the model`s two components is presented. Various applications to the analysis of long bone structures, such as the ulna and radius, are derived from the model, namely, data compression, comparison of 3-D shapes, segmentation into 3-D primitives, and torsion and curvature analysis. The relevance of the method to morphometry and to clinical applications is discussed.

  12. Growth and Potential Damage of Human Bone-Derived Cells Cultured on Fresh and Aged C60/Ti Films

    PubMed Central

    Kopova, Ivana; Lavrentiev, Vasily; Vacik, Jiri; Bacakova, Lucie

    2015-01-01

    Thin films of binary C60/Ti composites, with various concentrations of Ti ranging from ~ 25% to ~ 70%, were deposited on microscopic glass coverslips and were tested for their potential use in bone tissue engineering as substrates for the adhesion and growth of bone cells. The novelty of this approach lies in the combination of Ti atoms (i.e., widely used biocompatible material for the construction of stomatological and orthopedic implants) with atoms of fullerene C60, which can act as very efficient radical scavengers. However, fullerenes and their derivatives are able to generate harmful reactive oxygen species and to have cytotoxic effects. In order to stabilize C60 molecules and to prevent their possible cytotoxic effects, deposition in the compact form of Ti/C60 composites (with various Ti concentrations) was chosen. The reactivity of C60/Ti composites may change in time due to the physicochemical changes of molecules in an air atmosphere. In this study, we therefore tested the dependence between the age of C60/Ti films (from one week to one year) and the adhesion, morphology, proliferation, viability, metabolic activity and potential DNA damage to human osteosarcoma cells (lines MG-63 and U-2 OS). After 7 days of cultivation, we did not observe any negative influence of fresh or aged C60/Ti layers on cell behavior, including the DNA damage response. The presence of Ti atoms resulted in improved properties of the C60 layers, which became more suitable for cell cultivation. PMID:25875338

  13. Comparison of the osteogenic potential of mesenchymal stem cells from the bone marrow and adipose tissue of young dogs

    PubMed Central

    2014-01-01

    Background The aim of the present study was to compare the osteogenic potential of mesenchymal stem cells extracted from the bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) of young dogs. The following parameters were assessed: dimethyl thiazolyl diphenyl tetrazolium (MTT) conversion, alkaline phosphatase (ALP) activity, collagen and mineralised matrix synthesis, and the expressions of osterix, bone sialoprotein (BSP), and osteocalcin (OC). Results MTT conversion was greater in BM-MSCs compared to AD-MSCs after 14 and 21 days of differentiation; ALP activity was greater in differentiated AD-MSCs on day 7; collagen synthesis was greater in BM-MSCs on days 14 and 21; the percentage of mineralized area per field was greater in BM-MSCs compared to AD-MSCs; osterix expression was greater in BM-MSCs in days 14 and 21, and BSP and OC expression levels were greater in BM-MSCs at all the investigation time-points. Conclusions It was concluded that the osteogenic potential was greater in BM-MSCs than AD-MSCs when extracted from young dogs. PMID:25178540

  14. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials.

    PubMed

    Kawasaki, Haruhisa; Guan, Jianjun; Tamama, Kenichi

    2010-07-02

    Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study.

  15. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials

    SciTech Connect

    Kawasaki, Haruhisa; Guan, Jianjun; Tamama, Kenichi

    2010-07-02

    Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study.

  16. Impact of prophylactic CpG Oligodeoxynucleotide application on implant-associated Staphylococcus aureus bone infection.

    PubMed

    Sethi, Shneh; Thormann, Ulrich; Sommer, Ursula; Stötzel, Sabine; Mohamed, Walid; Schnettler, Reinhard; Domann, Eugen; Chakraborty, Trinad; Alt, Volker

    2015-09-01

    TLR-9 ligand CpG oligodeoxynucleotide type B (CpG ODN) induces a proinflammatory environment. We evaluated the effects of a preoperative CpG ODN application in an implant-associated Staphylococcus aureus bone infection model by monitoring bacterial loads and cytokine and chemokine levels. A total of 95 rats were used in four different groups: CpG ODN group (group 1; n=25), non-CpG-ODN group (group 2; n=25); saline pretreatment (group 3; n=25), and one uninfected group (group 4; n=20). A single dose of CpG-ODN was administered to the left tibialis anterior muscle 3days prior to surgery and the tibia midshaft was osteotomized, stabilized by an intramedullary implant and subsequently contaminated with 10(3) colony forming units (CFUs) of S. aureus in groups 1-3. The osteotomy gap in animals of group 4 was not contaminated with S. aureus and those animals did not receive any pretreatment. CpG ODN administration resulted in significant reduction of the bacterial load in tibia tissue homogenate and on the implant surface on day 1 post-infection compared to non-CpG-ODN pretreatment (p<0.05; p<0.05). Reductions in bacterial CFUs, compared to non-treated (saline) controls, were approximately 67% and 77% for bone tissue homogenates and implants. No bacteria were detected in uninfected rats. Early reduction of bacterial CFUs in the tibia was accompanied by increased levels of proinflammatory mediators MIP-2, IL-1β and RANTES in bone tissue milieu of the CpG ODN treated group compared to controls. At day 42 post-infection, bone marrow tissue of rats pretreated with CpG ODN had comparable high bacterial CFU numbers as the non-CpG ODN or saline treated groups. Microbiological analysis of implants removed from CpG ODN treated rats showed high bacterial growth densities on their surfaces which were not different from those observed in controls. In histology, all animals of groups 1-3 showed established infected non-unions. Additionally, inflammatory mediator profiles in bone

  17. Bacteriophages--potential for application in wastewater treatment processes.

    PubMed

    Withey, S; Cartmell, E; Avery, L M; Stephenson, T

    2005-03-01

    Bacteriophages are viruses that infect and lyse bacteria. Interest in the ability of phages to control bacterial populations has extended from medical applications into the fields of agriculture, aquaculture and the food industry. Here, the potential application of phage techniques in wastewater treatment systems to improve effluent and sludge emissions into the environment is discussed. Phage-mediated bacterial mortality has the potential to influence treatment performance by controlling the abundance of key functional groups. Phage treatments have the potential to control environmental wastewater process problems such as: foaming in activated sludge plants; sludge dewaterability and digestibility; pathogenic bacteria; and to reduce competition between nuisance bacteria and functionally important microbial populations. Successful application of phage therapy to wastewater treatment does though require a fuller understanding of wastewater microbial community dynamics and interactions. Strategies to counter host specificity and host cell resistance must also be developed, as should safety considerations regarding pathogen emergence through transduction.

  18. An experimental study on the application of radionuclide imaging in repair of the bone defect.

    PubMed

    Zhu, Weimin; Wang, Daping; Zhang, Xiaojun; Lu, Wei; Liu, Jianquan; Peng, Liangquan; Li, Hao; Han, Yun; Zeng, Yanjun

    2011-08-01

    The aim of our study was to validate the effect of radionuclide imaging in early monitoring of the bone's reconstruction, the animal model of bone defect was made on the rabbits repaired with HA artificial bone. The ability of bone defect repair was evaluated by using radionuclide bone imaging at 2, 4, 8 and 12 weeks postoperatively. The results indicate that the experimental group stimulated more bone formation than that of the control group. The differences of the bone reconstruction ability were statistically significant (p<0.05). The nano-HA artificial has good bone conduction, and it can be used for the treatment of bone defects. Radionuclide imaging may be an effective and first choice method for the early monitoring of the bone's reconstruction.

  19. A study of stress-free living bone and its application to space flight

    NASA Technical Reports Server (NTRS)

    Leblanc, A.; Spira, M.

    1983-01-01

    Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

  20. In vitro and in vivo degradation evaluation of novel iron-bioceramic composites for bone implant applications.

    PubMed

    Ulum, M F; Arafat, A; Noviana, D; Yusop, A H; Nasution, A K; Abdul Kadir, M R; Hermawan, H

    2014-03-01

    Biodegradable metals such as magnesium, iron and their alloys have been known as potential materials for temporary medical implants. However, most of the studies on biodegradable metals have been focusing on optimizing their mechanical properties and degradation behavior with no emphasis on improving their bioactivity behavior. We therefore investigated the possibility of improving iron biodegradation rate and bioactivity by incorporating various bioactive bioceramics. The iron-based bioceramic (hydroxyapatite, tricalcium phosphate and biphasic calcium phosphate) composites were prepared by mechanical mixing and sintering process. Degradation studies indicated that the addition of bioceramics lowered the corrosion potential of the composites and slightly increased their corrosion rate compared to that of pure iron. In vitro cytotoxicity results showed an increase of cellular activity when rat smooth muscle cells interacted with the degrading composites compared to pure iron. X-ray radiogram analysis showed a consistent degradation progress with that found in vivo and positive tissue response up to 70 days implantation in sheep animal model. Therefore, the iron-based bioceramic composites have the potential to be used for biodegradable bone implant applications.

  1. Effect of hyaluronic acid in bone formation and its applications in dentistry.

    PubMed

    Zhao, Ningbo; Wang, Xin; Qin, Lei; Zhai, Min; Yuan, Jing; Chen, Ji; Li, Dehua

    2016-06-01

    Hyaluronic acid (HA), the simplest glycosaminoglycan, participates in several important biological procedures, including mediation of cellular signaling, regulation of cell adhesion and proliferation, and manipulation of cell differentiation. The effect of HA on cell proliferation and differentiation depends on its molecular weight (MW) and concentration. Moreover, the properties of high viscosity, elasticity, highly negative charge, biocompatibility, biodegradability, and nonimmunogenicity make HA attractive in tissue engineering and disease treatment. This review comprises an overview of the effect of HA on cell proliferation and differentiation in vitro, the role of HA in bone regeneration in vivo, and the clinical applications of HA in dentistry, focusing on the mechanism underlining the effect of MW and concentration of HA on cell proliferation and osteogenic differentiation. It is expected that practical progress of HA both in laboratory-based experiments and clinical applications will be achieved in the next few years. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1560-1569, 2016.

  2. Reduction of bone resorption by the application of fibrin glue in the reconstruction of the alveolar cleft.

    PubMed

    Segura-Castillo, José L; Aguirre-Camacho, Humberto; González-Ojeda, Alejandro; Michel-Perez, Jorge

    2005-01-01

    A major complication in 30% to 75% of cases of surgical treatment of alveolar cleft is resorption of the bone graft. A treatment alternative is the application of fibrin glue, which has the capacity to favor the integration of the graft. The main objective of the study was to evaluate if the use of the fibrin glue reduces bone resorption when it is applied locally. The authors designed a randomized clinical trial. Patients were divided into two groups: group 1, fibrin glue; and group 2, control. Pre- and postoperative graft volume, bone density, bone quality (Lekholm and Zarb, and Norton and Gamble classifications), and postoperative complications were evaluated. The follow-up for all patients was 3 months after discharge. Twenty-seven patients were surgically treated, 13 in group 1 and 14 in group 2. Group 1 had increased graft volume compared with group 2 (64.32 cm v 21.70 cm; P < 0.0001). Bone density was higher in group 1 than in group 2 (396.57 v 245.68; P > 0.076). Bone quality was type 1, 2 and 3 and 4 in group 1. Resorption in group 2 was 62.26%; in group 1, it was 29.72% (P > 0.081). The observed complications were infection and dehiscence of sutures (P > 0.537). The authors conclude that the fibrin glue significantly diminishes bone resorption, allowing improved graft integration and quality.

  3. Thermophilic and alkaliphilic Actinobacteria: biology and potential applications.

    PubMed

    Shivlata, L; Satyanarayana, Tulasi

    2015-01-01

    Microbes belonging to the phylum Actinobacteria are prolific sources of antibiotics, clinically useful bioactive compounds and industrially important enzymes. The focus of the current review is on the diversity and potential applications of thermophilic and alkaliphilic actinobacteria, which are highly diverse in their taxonomy and morphology with a variety of adaptations for surviving and thriving in hostile environments. The specific metabolic pathways in these actinobacteria are activated for elaborating pharmaceutically, agriculturally, and biotechnologically relevant biomolecules/bioactive compounds, which find multifarious applications.

  4. Survey of advanced nuclear technologies for potential applications of sonoprocessing.

    PubMed

    Rubio, Floren; Blandford, Edward D; Bond, Leonard J

    2016-09-01

    Ultrasonics has been used in many industrial applications for both sensing at low power and processing at higher power. Generally, the high power applications fall within the categories of liquid stream degassing, impurity separation, and sonochemical enhancement of chemical processes. Examples of such industrial applications include metal production, food processing, chemical production, and pharmaceutical production. There are many nuclear process streams that have similar physical and chemical processes to those applications listed above. These nuclear processes could potentially benefit from the use of high-power ultrasonics. There are also potential benefits to applying these techniques in advanced nuclear fuel cycle processes, and these benefits have not been fully investigated. Currently the dominant use of ultrasonic technology in the nuclear industry has been using low power ultrasonics for non-destructive testing/evaluation (NDT/NDE), where it is primarily used for inspections and for characterizing material degradation. Because there has been very little consideration given to how sonoprocessing can potentially improve efficiency and add value to important process streams throughout the nuclear fuel cycle, there are numerous opportunities for improvement in current and future nuclear technologies. In this paper, the relevant fundamental theory underlying sonoprocessing is highlighted, and some potential applications to advanced nuclear technologies throughout the nuclear fuel cycle are discussed.

  5. Adipogenic potentials of mesenchymal stem cells from human bone marrow, umbilical cord and adipose tissue are different.

    PubMed

    Chi, Ying; Han, Zhi-Bo; Xu, Fang-Yun; Wang, You-Wei; Feng, Xiao-Ming; Chen, Fang; Ma, Feng-Xia; Du, Wen-Jing; Han, Zhong-Chao

    2014-06-01

    Mesenchymal stem cells (MSCs) could be obtained from many sources, and there are differences between them. This study was purposed to compare and analyze the basic biological characteristics of umbilical cord, adipose tissue-and bone marrow-derived MSC (UC-MSCs, AD-MSCs and BM-MSCs). The MSCs were isolated from umbilical cord, adipose tissue and bone marrow were cultured; the morphology of UC-MSCs, AD-MSCs and BM-MSCs was observed by using microscopy; the immunophenotype, differentiation potential and expression of peroxisome proliferation-activated receptor-γ (PPAR-γ) mRNA were detected by using flow cytometry, differentiation test (von kossais and 0:1 red O staining) and quantitative fluorescent PCR, respectively. The results showed that the UC-MSCs, AD-MSCs and BM-MSCs displayed similar morphology under confocal microscope after being stained with rhodamine phalloidin and DAPL. The immunophenotypes of these three originated cells conform to coincide with identification criterion for MSCs, and showed similar expression level. During adipogenic induction the adipogenic potential of these MSCs was different, AD-MSCs exhibited the highest adipogenic potential, UC-MSCs displayed the lowest, while potential of BM-MSCs get between; however, the osteogenic differentiation potential of UC-MSCs, AD-MSCs and BM-MSCs was similar. The PCR detection showed that the expression level of PPAR-γ mRNA was the highest in AD-MSCs and the lowest in UC-MSCs, while expression level in BM-MSCs get between, these results were identical with the adipogenic potential, suggest that the difference of adipogenic potential in 3 kinds of MSCs was associated with basic expression level of PPAR-γ mRNA. It is concluded that UC-MSCs, AD-MSCs and BM-MSCs exhibit similar morphology, the immunophenotypes of these MSCs coincide with identification criterion for MSCs, the osteogenic potential of these MSCs is similar, while the adipogenic potential and the expression level of PPAR-γ mRNA are

  6. Erythropoietin is involved in the angiogenic potential of bone marrow macrophages in multiple myeloma.

    PubMed

    De Luisi, Annunziata; Binetti, Laura; Ria, Roberto; Ruggieri, Simona; Berardi, Simona; Catacchio, Ivana; Racanelli, Vito; Pavone, Vincenzo; Rossini, Bernardo; Vacca, Angelo; Ribatti, Domenico

    2013-10-01

    Erythropoietin (Epo) is the crucial cytokine regulator of red blood cell production, and recombinant human erythropoietin (rHuEpo) is widely used in clinical practice for the treatment of anemia, primarily in kidney disease and in cancer. Increasing evidence suggests several biological roles for Epo and its receptor, Epo-R, unrelated to erythropoiesis, including angiogenesis. Epo-R has been found expressed in various non-haematopoietic cells and tissues, and in cancer cells. Here, we detected the expression of Epo-R in bone marrow-derived macrophages (BMMAs) from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) patients and assessed whether Epo/Epo-R axis plays a role in MM macrophage-mediated angiogenesis. We found that Epo-R is over-expressed in BMMAs from MM patients with active disease compared to MGUS patients. The treatment of BMMAs with rHuEpo significantly increased the expression and secretion of key pro-angiogenic mediators, such as vascular endothelial growth factor, hepatocyte growth factor and monocyte chemotactic protein (MCP-1/CCL-2), through activation of JAK2/STAT5 and PI3 K/Akt pathways. In addition, the conditioned media harvested from rHuEpo-treated BMMAs enhanced bone marrow-derived endothelial cell migration and capillary morphogenesis in vitro, and induced angiogenesis in the chorioallantoic membrane of chick embryos in vivo. Furthermore, we found an increase in the circulating levels of several pro-angiogenic cytokines in serum of MM patients with anemia under treatment with Epo. Our findings highlight the direct effect of rHuEpo on macrophage-mediated production of pro-angiogenic factors, suggesting that Epo/Epo-R pathway may be involved in the regulation of angiogenic response occurring in MM.

  7. The Role of Semaphorin 3A in Bone Remodeling

    PubMed Central

    Li, Zhenxia; Hao, Jin; Duan, Xin; Wu, Nan; Zhou, Zongke; Yang, Fan; Li, Juan; Zhao, Zhihe; Huang, Shishu

    2017-01-01

    Bone remodeling occurs at the bone surface throughout adult life and associates bony quantity and quality. This process is a balance between the osteoblastic bone formation and osteoclastic bone resorption, which cross-talks together. Semaphorin 3A is a membrane-associated secreted protein and regarded as a diffusible axonal chemorepellent, which has been identified in the involvement of bone resorption and formation synchronously. However, the role of Semaphorin 3A in bone homeostasis and diseases remains elusive, in particular the association to osteoblasts and osteoclasts. In this review article, we summarize recent progress of Semaphorin 3A in the bone mass, homeostasis, and diseases and discuss the novel application of nerve-based bone regeneration. This will facilitate the understanding of Semaphorin 3A in skeletal biology and shed new light on the modulation and potential treatment in the bone disorders. PMID:28293171

  8. Impact and risk factors of post-stroke bone fracture.

    PubMed

    Huo, Kang; Hashim, Syed I; Yong, Kimberley L Y; Su, Hua; Qu, Qiu-Min

    2016-02-20

    Bone fracture occurs in stroke patients at different times during the recovery phase, prolonging recovery time and increasing medical costs. In this review, we discuss the potential risk factors for post-stroke bone fracture and preventive methods. Most post-stroke bone fractures occur in the lower extremities, indicating fragile bones are a risk factor. Motor changes, including posture, mobility, and balance post-stroke contribute to bone loss and thus increase risk of bone fracture. Bone mineral density is a useful indicator for bone resorption, useful to identify patients at risk of post-stroke bone fracture. Calcium supplementation was previously regarded as a useful treatment during physical rehabilitation. However, recent data suggests calcium supplementation has a negative impact on atherosclerotic conditions. Vitamin D intake may prevent osteoporosis and fractures in patients with stroke. Although drugs such as teriparatide show some benefits in preventing osteoporosis, additional clinical trials are needed to determine the most effective conditions for post-stroke applications.

  9. Laser wakefield accelerator based light sources: potential applications and requirements

    SciTech Connect

    Albert, F.; Thomas, A. G.; Mangles, S. P.D.; Banerjee, S.; Corde, S.; Flacco, A.; Litos, M.; Neely, D.; Viera, J.; Najmudin, Z.; Bingham, R.; Joshi, C.; Katsouleas, T.

    2015-01-15

    In this article we review the prospects of laser wakefield accelerators as next generation light sources for applications. This work arose as a result of discussions held at the 2013 Laser Plasma Accelerators Workshop. X-ray phase contrast imaging, X-ray absorption spectroscopy, and nuclear resonance fluorescence are highlighted as potential applications for laser-plasma based light sources. We discuss ongoing and future efforts to improve the properties of radiation from plasma betatron emission and Compton scattering using laser wakefield accelerators for these specific applications.

  10. Differential response of bone and kidney to ACEI in db/db mice: A potential effect of captopril on accelerating bone loss.

    PubMed

    Zhang, Yan; Li, Xiao-Li; Sha, Nan-Nan; Shu, Bing; Zhao, Yong-Jian; Wang, Xin-Luan; Xiao, Hui-Hui; Shi, Qi; Wong, Man-Sau; Wang, Yong-Jun

    2017-04-01

    The components of renin-angiotensin system (RAS) are expressed in the kidney and bone. Kidney disease and bone injury are common complications associated with diabetes. This study aimed to investigate the effects of an angiotensin-converting enzyme inhibitor, captopril, on the kidney and bone of db/db mice. The db/db mice were orally administered by gavage with captopril for 8weeks with db/+ mice as the non-diabetic control. Serum and urine biochemistries were determined by standard colorimetric methods or ELISA. Histological measurements were performed on the kidney by periodic acid-schiff staining and on the tibial proximal metaphysis by safranin O and masson-trichrome staining. Trabecular bone mass and bone quality were analyzed by microcomputed tomography. Quantitative polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. Captopril significantly improved albuminuria and glomerulosclerosis in db/db mice, and these effects might be attributed to the down-regulation of angiotensin II expression and the expression of its down-stream profibrotic factors in the kidney, like connective tissue growth factor and vascular endothelial growth factor. Urinary excretion of calcium and phosphorus markedly increased in db/db mice in response to captopril. Treatment with captopril induced a decrease in bone mineral density and deterioration of trabecular bone at proximal metaphysis of tibia in db/db mice, as shown in the histological and reconstructed 3-dimensional images. Even though captopril effectively reversed the diabetes-induced changes in calcium-binding protein 28-k and vitamin D receptor expression in the kidney as well as the expression of RAS components and bradykinin receptor-2 in bone tissue, treatment with captopril increased the osteoclast-covered bone surface, reduced the osteoblast-covered bone surface, down-regulated the expression of type 1 collagen and transcription factor runt-related transcription

  11. Study of a new bone-targeting titanium implant-bone interface.

    PubMed

    Liu, Xiangning; Zhang, Ye; Li, Shaobing; Wang, Yayu; Sun, Ting; Li, Zejian; Cai, Lizhao; Wang, Xiaogang; Zhou, Lei; Lai, Renfa

    New strategies involving bone-targeting titanium (Ti) implant-bone interface are required to enhance bone regeneration and osseointegration for orthopedic and dental implants, especially in osteoporotic subjects. In this study, a new dual-controlled, local, bone-targeting delivery system was successfully constructed by loading tetracycline-grafted simvastatin (SV)-loaded polymeric micelles in titania nanotube (TNT) arrays, and a bone-targeting Ti implant-bone interface was also successfully constructed by implanting the delivery system in vivo. The biological effects were evaluated both in vitro and in vivo. The results showed that Ti surfaces with TNT-bone-targeting micelles could promote cytoskeletal spreading, early adhesion, alkaline phosphatase activity, and extracellular osteocalcin concentrations of rat osteoblasts, with concomitant enhanced protein expression of bone morphogenetic protein (BMP)-2. A single-wall bone-defect implant model was established in normal and ovariectomized rats as postmenopausal osteoporosis models. Microcomputed tomography imaging and BMP-2 expression in vivo demonstrated that the implant with a TNT-targeting micelle surface was able to promote bone regeneration and osseointegration in both animal models. Therefore, beneficial biological effects were demonstrated both in vitro and in vivo, which indicated that the bone-targeting effects of micelles greatly enhance the bioavailability of SV on the implant-bone interface, and the provision of SV-loaded targeting micelles alone exhibits the potential for extensive application in improving local bone regeneration and osseointegration, especially in osteoporotic subjects.

  12. Study of a new bone-targeting titanium implant–bone interface

    PubMed Central

    Liu, Xiangning; Zhang, Ye; Li, Shaobing; Wang, Yayu; Sun, Ting; Li, Zejian; Cai, Lizhao; Wang, Xiaogang; Zhou, Lei; Lai, Renfa

    2016-01-01

    New strategies involving bone-targeting titanium (Ti) implant–bone interface are required to enhance bone regeneration and osseointegration for orthopedic and dental implants, especially in osteoporotic subjects. In this study, a new dual-controlled, local, bone-targeting delivery system was successfully constructed by loading tetracycline-grafted simvastatin (SV)-loaded polymeric micelles in titania nanotube (TNT) arrays, and a bone-targeting Ti implant–bone interface was also successfully constructed by implanting the delivery system in vivo. The biological effects were evaluated both in vitro and in vivo. The results showed that Ti surfaces with TNT–bone-targeting micelles could promote cytoskeletal spreading, early adhesion, alkaline phosphatase activity, and extracellular osteocalcin concentrations of rat osteoblasts, with concomitant enhanced protein expression of bone morphogenetic protein (BMP)-2. A single-wall bone-defect implant model was established in normal and ovariectomized rats as postmenopausal osteoporosis models. Microcomputed tomography imaging and BMP-2 expression in vivo demonstrated that the implant with a TNT-targeting micelle surface was able to promote bone regeneration and osseointegration in both animal models. Therefore, beneficial biological effects were demonstrated both in vitro and in vivo, which indicated that the bone-targeting effects of micelles greatly enhance the bioavailability of SV on the implant–bone interface, and the provision of SV-loaded targeting micelles alone exhibits the potential for extensive application in improving local bone regeneration and osseointegration, especially in osteoporotic subjects. PMID:27932879

  13. Local gentamicin application does not interfere with bone healing in a rat model.

    PubMed

    Fassbender, M; Minkwitz, S; Kronbach, Z; Strobel, C; Kadow-Romacker, A; Schmidmaier, G; Wildemann, B

    2013-08-01

    For the prophylaxis and treatment of bony infections antibiotics are locally used. Since several decades antibiotics mixed with bone cement (methylmethacrylate) are successfully used in prosthetic surgery and a gentamicin coated tibial nail is approved in Europe for fracture stabilization. The goal of the present study was to investigate if gentamicin, locally applied from a polymeric coating of intramedullary nails, might interfere with the bone healing process. Female Sprague Dawley rats (n = 72) were used and the tibiae were intramedullary stabilized with Kirschner-wires (k-wires) after osteotomy. This model was established earlier and shows a delayed healing with a prolonged inflammatory reaction. The open approach is clinically more relevant compared to a closed one because it mimics the clinically critical case of an open fracture, which has a higher risk of infection. The k-wire was either coated with the polymer poly(d,l-lactide) (control group) or with 10% gentamicin incorporated into the polymer (gentamicin group). In vivo μCT analyses were performed at days 10, 28, 42, and 84 after osteotomy. Mechanical torsional testing and histological evaluation were done at the days of sacrifice: 28, 42, and 84. The μCT analyses revealed an increase in tissue mineral density (TMD) over the healing period in both groups. In the control group, the torsional stiffness and maximum load did not reach the values of the intact contralateral side at any time point. At day 84 the gentamicin treated tibiae, however, showed significantly better maximum load compared to the control group. The histology showed no bony bridging in the control, whereas in 2 of 5 calluses of the gentamicin group mineralized bridging occurred. Significantly more mineralized tissue was measured in the gentamicin group. This study shows that the local gentamicin application does not negatively interfere with the long term healing process. Local infection prophylaxis is effective without negative

  14. Age-related alterations in mesenchymal stem cells related to shift in differentiation from osteogenic to adipogenic potential: implication to age-associated bone diseases and defects.

    PubMed

    Kim, MiJung; Kim, ChanWha; Choi, Yu Suk; Kim, MinHwan; Park, ChanJeoung; Suh, Yousin

    2012-05-01

    Mesenchymal stem cells (MSC) have attracted considerable attention in the fields of cell and gene therapy due to their intrinsic ability to differentiate into multiple lineages. The various therapeutic applications involving MSC require initial expansion and/or differentiation in vitro prior to clinical use. However, serial passages of MSC in culture lead to decreased differentiation potential and stem cell characteristics, eventually inducing cellular aging which will limit the success of cell-based therapeutic interventions. Here we review the age-related changes that occur in MSC with a special focus on the shift of differentiation potential from osteogenic to adipogenic lineage during the MSC aging processes and how aging causes this preferential shift by oxidative stress and/or energy metabolism defect. Oxidative stress-related signals and some microRNAs affect the differentiation potential shift of MSC by directly targeting key regulatory factors such as Runx-2 or PPAR-γ, and energy metabolism pathway is involved as well. All information described here including transcription factors, microRNAs and FoxOs could be used towards development of treatment regimens for age-related bone diseases and related defects based on mutually exclusive lineage fate determination of MSC.

  15. Potential applications of electron emission membranes in medicine

    NASA Astrophysics Data System (ADS)

    Bilevych, Yevgen; Brunner, Stefan E.; Chan, Hong Wah; Charbon, Edoardo; van der Graaf, Harry; Hagen, Cornelis W.; Nützel, Gert; Pinto, Serge D.; Prodanović, Violeta; Rotman, Daan; Santagata, Fabio; Sarro, Lina; Schaart, Dennis R.; Sinsheimer, John; Smedley, John; Tao, Shuxia; Theulings, Anne M. M. G.

    2016-02-01

    With a miniaturised stack of transmission dynodes, a noise free amplifier is being developed for the detection of single free electrons, with excellent time- and 2D spatial resolution and efficiency. With this generic technology, a new family of detectors for individual elementary particles may become possible. Potential applications of such electron emission membranes in medicine are discussed.

  16. Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential.

    PubMed

    Ng, Ashley P; Kauppi, Maria; Metcalf, Donald; Di Rago, Ladina; Hyland, Craig D; Alexander, Warren S

    2012-02-14

    Hematopoietic progenitor cells are the progeny of hematopoietic stem cells that coordinate the production of precise numbers of mature blood cells of diverse functional lineages. Identification of cell-surface antigen expression associated with hematopoietic lineage restriction has allowed prospective isolation of progenitor cells with defined hematopoietic potential. To clarify further the cellular origins of megakaryocyte commitment, we assessed the in vitro and in vivo megakaryocyte and platelet potential of defined progenitor populations in the adult mouse bone marrow. We show that megakaryocytes arise from CD150(+) bipotential progenitors that display both platelet- and erythrocyte-producing potential in vivo and that can develop from the Flt3(-) fraction of the pregranulocyte-macrophage population. We define a bipotential erythroid-megakaryocyte progenitor population, the CD150(+)CD9(lo)endoglin(lo) fraction of Lin(-)cKit(+)IL7 receptor alpha(-)FcγRII/III(lo)Sca1(-) cells, which contains the bulk of the megakaryocyte colony-forming capacity of the bone marrow, including bipotential megakaryocyte-erythroid colony-forming capacity, and can generate both erythrocytes and platelets efficiently in vivo. This fraction is distinct from the CD150(+)CD9(hi)endoglin(lo) fraction, which contains bipotential precursors with characteristics of increased megakaryocytic maturation, and the CD150(+)CD9(lo)endoglin(hi) fraction, which contains erythroid lineage-committed cells. Finally, we demonstrate that bipotential erythroid-megakaryocyte progenitor and CD150(+)CD9(hi)endoglin(lo) cells are TPO-responsive and that the latter population specifically expands in the recovery from thrombocytopenia induced by anti-platelet serum.

  17. FACILE SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF CELLULOSE-CHITOSAN-HYDROXYAPATITE COMPOSITE MATERIAL, A POTENTIAL MATERIAL FOR BONE TISSUE ENGINEERING

    PubMed Central

    Mututuvari, Tamutsiwa M.; Harkins, April L.

    2013-01-01

    Hydroxyapatite (HAp) is often used as a bone-implant material because it is biocompatible and osteoconductive. However, HAp possesses poor rheological properties and it is inactive against disease-causing microbes. To improve these properties, we developed a green method to synthesize multifunctional composites containing: (1) cellulose (CEL) to impart mechanical strength; (2) chitosan (CS) to induce antibacterial activity thereby maintaining a microbe-free wound site; and (3) HAp. In this method, CS and CEL were co-dissolved in an ionic liquid (IL) and then regenerated from water. HAp was subsequently formed in situ by alternately soaking [CEL+CS] composites in aqueous solutions of CaCl2 and Na2HPO4. At least 88% of IL used was recovered for reuse by distilling the aqueous washings of [CEL+CS]. The composites were characterized using FTIR, XRD and SEM. These composites retained the desirable properties of their constituents. For example, the tensile strength of the composites was enhanced 1.9X by increasing CEL loading from 20% to 80%. Incorporating CS in the composites resulted in composites which inhibited the growth of both Gram positive (MRSA, S. aureus and VRE) and Gram negative (E. coli and P. aeruginosa) bacteria. These findings highlight the potential use of [CEL+CS+HAp] composites as scaffolds in bone tissue engineering. PMID:23595871

  18. Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standardizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

    DTIC Science & Technology

    2011-08-01

    osteoblasts and marked by a DKK3 reporter leads to fibrocartilage and periosteal development; (4) the cryohistology that facilitates the rapid and...host bone and in fact when placed in a segmental defects, they are inhibitory to the periosteal response characteristic of a bone fracture. Because...Utilizing mice harboring multiple GFP reporters that identify cells at different levels of osteoblast differentiation, he examined a closed tibial fracture

  19. Clinoptilolite/PCL-PEG-PCL composite scaffolds for bone tissue engineering applications.

    PubMed

    Pazarçeviren, Engin; Erdemli, Özge; Keskin, Dilek; Tezcaner, Ayşen

    2017-03-01

    The aim of this study was to prepare and characterize highly porous clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) composite scaffolds. Scaffolds with different clinoptilolite contents (10% and 20%) were fabricated with reproducible solvent-free powder compression/particulate leaching technique. The scaffolds had interconnective porosity in the range of 55-76%. Clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) scaffolds showed negligible degradation within eight weeks and displayed less water uptake and higher bioactivity than poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) scaffolds. The presence of clinoptilolite improved the mechanical properties. Highest compressive strength (5.6 MPa) and modulus (114.84 MPa) were reached with scaffold group containing 20% clinoptilolite. In vitro protein adsorption capacity of the scaffolds was also higher for clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) scaffolds. These scaffolds had 0.95 mg protein/g scaffold adsorption capacity and also higher osteoinductivity in terms of enhanced ALP, OSP activities and intracellular calcium deposition. Stoichiometric apatite deposition (Ca/P=1.686) was observed during cellular proliferation analysis with human fetal osteoblasts cells. Thus, it can be suggested that clinoptilolite/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) composite scaffolds could be promising carriers for enhancement of bone regeneration in bone tissue engineering applications.

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

    PubMed

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

    2016-11-21

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

  1. Applicability of equine hydroxyapatite collagen (eHAC) bone blocks for lateral augmentation of the alveolar crest. A histological and histomorphometric analysis in rats.

    PubMed

    Zecha, P J; Schortinghuis, J; van der Wal, J E; Nagursky, H; van den Broek, K C; Sauerbier, S; Vissink, A; Raghoebar, G M

    2011-05-01

    This study assessed the mechanical characteristics, biocompatibility and osteoconductive properties of an equine hydroxyapatite collagen (eHAC) bone block when applied as a bone substitute for lateral augmentation of rat mandible. 96 rats underwent lateral augmentation of the mandible, using two substitute bone blocks (eHAC or Bio-Oss spongiosa) or autologous bone grafts. Signs of inflammation, amount of bone formation and ingrowth of bone into the bone blocks were assessed at 1 and 3 months. eHAC blocks were mechanically rigid and could be fixed firmly and easily. Bio-Oss spongiosa blocks were brittle and fixation was difficult. eHAC and Bio-Oss spongiosa blocks were biocompatible and induced few or no signs of inflammation. Inflammation prevalence between the groups was not statistically different. Bone formation and bone growth into the blocks was significantly higher in eHAC than Bio-Oss spongiosa blocks, but lower than in autologous bone grafts (after 1 and 3 months). Regression analysis showed that the autologous bone graft predicted new bone formation at both time points. The eHAC block was only a predictor at 1 month; a trend was found at 3 months. The application of biodegradable membranes was not related to more bone ingrowth.

  2. Cancer-reactive memory T cells from bone marrow: Spontaneous induction and therapeutic potential (Review).

    PubMed

    Schirrmacher, Volker

    2015-12-01

    Cognate interactions between naïve tumor antigen (TA)-specific T cells and TA-presenting dendritic cells (DCs) are facilitated by secondary lymphoid organs such as lymph nodes or the spleen. These can result either in TA-specific tolerance or, depending on environmental costimulatory signals, in TA-specific immune responses. In the present review, we describe such events for the bone marrow (BM) when blood-borne TA, released from the primary tumor or expressed by blood circulating tumor cells or DCs enters the BM stroma and parenchyma. We argue that cognate T-DC interactions in the BM result in immune responses and generation of memory T cells (MTCs) rather than tolerance because T cells in the BM show an increased level of pre-activation. The review starts with the spontaneous induction of cancer-reactive MTCs in the BM and the involvement of such MTCs in the control of tumor dormancy. The main part deals with the therapeutic potency of BM MTCs. This is a new area of research in which the authors research group has performed pioneering studies which are summarized. These include studies in animal tumor models, studies with human cells in tumor xenotransplant models and clinical studies. Based on observations of an enormous expansion capacity, longevity and therapeutic capacity of BM MTCs, a hypothesis is presented which suggests the involvement of stem-like MTCs.

  3. Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential

    PubMed Central

    Zhang, Qun; Liu, Song; Li, Tong; Yuan, Lin; Liu, Hansen; Wang, Xueer; Wang, Fuwu; Wang, Shuanglian; Hao, Aijun; Liu, Dexiang; Wang, Zhen

    2016-01-01

    Bone marrow mesenchymal stem cells (BMSCs) transplantation has shown great promises for treating various brain diseases. However, poor viability of transplanted BMSCs in injured brain has limited the therapeutic efficiency. Hypoxia-ischemic injury is one of major mechanisms underlying the survival of transplanted BMSCs. We investigated the mechanism of preconditioning of BMSCs with hydrogen sulfide (H2S), which has been proposed as a novel therapeutic strategy for hypoxia-ischemic injury. In this study, we demonstrated that preconditioning of NaHS, a H2S donor, effectively suppressed hypoxia-ischemic-induced apoptosis whereby the rise in Bax/Bcl-2 ratio. Further analyses revealed Akt and ERK1/2 pathways were involved in the protective effects of NaHS. In addition, NaHS preconditioning increased secretion of BDNF and VEGF in BMSCs. Consistent with in vitro data, transplantation of NaHS preconditioned BMSCs in vivo further enhanced the therapeutic effects of BMSCs on neuronal injury and neurological recovery, associated with increased vessel density and upregulation of BDNF and VEGF in the ischemic tissue. These findings suggest that H2S could enhance the therapeutic effects of BMSCs. The underlying mechanisms might be due to enhanced capacity of BMSCs and upregulation of protective cytokines in the hypoxia tissue. PMID:27517324

  4. Biomimetic hydroxyapatite as a new consolidating agent for archaeological bone

    NASA Astrophysics Data System (ADS)

    North, Alexis E.

    Recent studies on calcareous stone and plaster consolidation have demonstrated considerable potential by bio-mimicking the growth of hydroxyapatite (HAP), the main mineralogical constituent of teeth and bone matrix. These initial conservation applications, together with significant fundamental research on the precipitation of HAP for bioengineering and biomedical applications, offer great promise in the use of HAP as a consolidating agent for archaeological bone and other similar materials such as archaeological teeth, ivory, and antler. Experimental research via the controlled application of diammonium phosphate (DAP) precursors to bone flour, modern bone samples, and archaeological bones, indicated the in situ formation of HAP with a simultaneous increase in the cohesiveness of friable bone material, while preserving the bone's physiochemical properties. These preliminary results point towards a promising new method in archaeological conservation.

  5. Reverse micelle mediated synthesis, processing, mechanical and biological characterization of hydroxyapatite nanopowders for bone graft application

    NASA Astrophysics Data System (ADS)

    Banerjee, Ashis

    Hydroxyapatite (HA) is the most widely used bioceramic material in bone graft applications because of its compositional similarity with natural bone. However, synthetic HA does not show similar mechanical and biological properties to the inorganic component of bone. Properties of ceramic material depend on starting materials, processing techniques, densification and microstructure of the final product. The objective of this research was to process HA whisker reinforced HA composite using HA nanopowders and whiskers. HA nanopowders with different length scale and morphology were synthesized by reverse micelle system using NP5 and NP12 as surfactants and cyclohexane as organic solvent. The lowest average aspect ratio was 1.357+/-0.39 with average particle size of 66 nm and the highest average aspect ratio was 7.277+/-3.227 with average length of 150 nm and width of 20 nm, were synthesized. Micron sized HA whiskers with aspect ratio between 20 and 50, average particle length of 15 mum and width of 400 nm was synthesized using urea as a precipitating agent. Desired microstructure was obtained after sintering with spherical HA nanopowder and whiskers along with dopants. Addition of whiskers decreased density of the sintered compacts. However, at 10 wt% whisker content sample showed microhardness and fracture toughness of 3.6 GPa and 1.5 MPa.m1/2, respectively, and a compressive strength of 80 MPa was obtained. Mineralization study in simulated body fluid (SBF) showed formation of apatite layer on the dense HA compacts indicating a good tendency of bond formation with natural bone. Cytotoxicity results showed excellent cell attachment on the HA surface. In the Appendices, 3 journal articles have been attached which describe synthesis, processing and characterization of undoped and doped PZT nanopowders. Free standing and agglomerated PZT nanopowders were synthesized by the sucrose templated method and the citrate nitrate autocombustion method. Particle size in the range

  6. Physical and Biological Modification of Polycaprolactone Electrospun Nanofiber by Panax Ginseng Extract for Bone Tissue Engineering Application.

    PubMed

    Pajoumshariati, Seyedramin; Yavari, Seyedeh Kimia; Shokrgozar, Mohammad Ali

    2016-05-01

    Medicinal plants as a therapeutic agent with osteogenic properties can enhance fracture-healing process. In this study, the osteo-inductive potential of Asian Panax Ginseng root extract within electrospun polycaprolactone (PCL) based nanofibers has been investigated. Scanning electron microscopy images revealed that all nanofibers were highly porous and beadles with average diameter ranging from 250 to 650 nm. The incorporation of ginseng extract improved the physical characteristics (i.e., hydrophilicity) of PCL nanofibers, as well as the mechanical properties. Although ginseng extract increased the degradation rate of pure PCL nanofibers, the porous structure and morphology of fibers did not change significantly after 42 days. It was found that nanofibrous scaffolds containing ginseng extract had higher proliferation (up to ~1.5 fold) compared to the pristine PCL. The qRT-PCR analysis demonstrated the addition of ginseng extract into PCL nanofibers induced significant expression of osteogenic genes (Osteocalcin, Runx-2 and Col-1) in MSCs in a concentration dependent manner. Moreover, higher calcium content, alkaline phosphatase activity and higher mineralization of MSCs were observed compared to the pristine PCL fibers. Our results indicated the promising potential of ginseng extract as an additive to enhance osteo-inductivity, mechanical and physical properties of PCL nanofibers for bone tissue engineering application.

  7. Bioactive calcium sulfate/magnesium phosphate cement for bone substitute applications.

    PubMed

    Yang, Guangyong; Liu, Jianli; Li, Fan; Pan, Zongyou; Ni, Xiao; Shen, Yue; Xu, Huazi; Huang, Qing

    2014-02-01

    A novel calcium sulfate/magnesium phosphate cement (CSMPC) composite was prepared and studied in the present work. The physical properties including the phases, the microstructures, the setting properties and the compressive strengths of the CSMPCs were studied. The bio-performances of the CSMPCs were comprehensively evaluated using in vitro simulated body fluid (SBF) method and in vitro cell culture. The dependence of the physical and chemical properties of the CSMPC on its composition and microstructure was studied in detail. It is found that the CSMPC composites exhibited mediate setting times (6-12 min) compared to the calcium sulfate (CS) and the magnesium phosphate cement (MPC). They showed an encapsulation structure in which the unconverted hexagonal prism CSH particles were embedded in the xerogel-like MPC matrix. The phase compositions and the mechanical properties of the CSMPCs were closely related to the content of MPC and the hardening process. The CSMPCs exhibited excellent bioactivity and good biocompatibility to support the cells to attach and proliferate on the surface. The CSMPC composite has the potential to serve as bone grafts for the bone regeneration.

  8. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  9. Functionalized bridged silsesquioxane-based nanostructured microspheres: performance as novel drug-delivery devices in bone tissue-related applications.

    PubMed

    Romeo, Hernán Esteban; Fanovich, María Alejandra

    2012-05-01

    this new class of functionalized hybrid microdevices as delivery systems into calcium phosphate materials with potential bone tissue-related drug-delivery applications.

  10. Locust bean gum: Exploring its potential for biopharmaceutical applications

    PubMed Central

    Dionísio, Marita; Grenha, Ana

    2012-01-01

    Polysaccharides have been finding, in the last decades, very interesting and useful applications in the biomedical and, specifically, in the biopharmaceutical field. Locust bean gum is a polysaccharide belonging to the group of galactomannans, being extracted from the seeds of the carob tree (Ceratonia siliqua). This polymer displays a number of appealing characteristics for biopharmaceutical applications, among which its high gelling capacity should be highlighted. In this review, we describe critical aspects of locust bean gum, contributing for its role in biopharmaceutical applications. Physicochemical properties, as well as strong and effective synergies with other biomaterials are described. The potential for in vivo biodegradation is explored and the specific biopharmaceutical applications are discussed. PMID:22923958

  11. Investigation on microstructure, composition, and cytocompatibility of natural pumice for potential biomedical application.

    PubMed

    Li, Xiyu; Yang, Weihu; Zou, Qin; Zuo, Yi

    2010-06-01

    In this study, the properties of Changbaishan natural pumice were characterized including the microstructure, porosity, mechanical strength, composition, harmful trace element content, and cytocompatibility. The results show that the natural pumice has a porous structure with a pore size ranging from 50 to 150 mum, an interconnective porosity of 80%, and a compressive strength of 1.72 +/- 0.12 MPa, which are adequate as a scaffold for bone tissue engineering. The natural pumice is mainly composed of silicate, and the content of harmful trace elements of arsenic (As), cadmium (Cd), and mercury (Hg) in the pumice are less than 3 ppm, whereas the content of plumbum (Pb) is less than 5 ppm, which can meet the requirement of China Medicine Standard regulation. Cytocompatibility of the pumice was also evaluated by culturing and seeding MG63 cells on the scaffold and with its medium extraction. The cells present good adhesion and proliferation and the pumice does not show a negative effect on the MG63 cells in vitro. A period of 11 days testing by 3-{4,5-dimethylthiazol-2yl}-2,5-diphenyl-2H-tetrazolium-bromide assay demonstrates that the pumice has little influence on the cell viability. This new investigation paves the way for further study on pumice's potential for biomedical applications, such as for bone tissue engineering scaffold.

  12. Micro- and nanostructured hydroxyapatite-collagen microcarriers for bone tissue-engineering applications.

    PubMed

    Perez, R A; Altankov, G; Jorge-Herrero, E; Ginebra, M P

    2013-05-01

    Novel hydroxyapatite (HA)-collagen microcarriers (MCs) with different micro/nanostructures were developed for bone tissue-engineering applications. The MCs were fabricated via calcium phosphate cement (CPC) emulsion in oil. Collagen incorporation in the liquid phase of the CPC resulted in higher MC sphericity. The MCs consisted of a porous network of entangled hydroxyapatite crystals, formed as a result of the CPC setting reaction. The addition of collagen to the MCs, even in an amount as small as 0.8 wt%, resulted in an improved interaction with osteoblast-like Saos-2 cells. The micro/nanostructure and the surface texture of the MCs were further tailored by modifying the initial particle size of the CPC. A synergistic effect between the presence of collagen and the nanosized HA crystals was found, resulting in significantly enhanced alkaline phosphatase activity on the collagen-containing nanosized HA MCs.

  13. Synchrotron Radiation and Energy Dispersive X-Ray Fluorescence Applications on Elemental Distribution in Human Hair and Bones

    SciTech Connect

    Carvalho, M.L.; Marques, A.F.; Brito, J.

    2003-01-24

    This work is an application of synchrotron microprobe X- Ray fluorescence in order to study elemental distribution along human hair samples of contemporary citizens. Furthermore, X-Ray fluorescence spectrometry is also used to analyse human bones of different historical periods: Neolithic and contemporary subjects. The elemental content in the bones allowed us to conclude about environmental contamination, dietary habits and health status influence in the corresponding citizens. All samples were collected post-mortem. Quantitative analysis was performed for Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr and Pb. Mn and Fe concentration were much higher in bones from pre-historic periods. On the contrary, Pb bone concentrations of contemporary subjects are much higher than in pre-historical ones, reaching 100 {mu}g g-1, in some cases. Very low concentrations for Co, Ni, Br and Rb were found in all the analysed samples. Cu concentrations, allows to distinguish Chalcolithic bones from the Neolithic ones. The distribution of trace elements along human hair was studied for Pb and the obtained pattern was consistent with the theoretical model, based on the diffusion of this element from the root and along the hair. Therefore, the higher concentrations in hair for Pb of contemporary individuals were also observed in the bones of citizens of the same sampling sites. All samples were analysed directly without any chemical treatment.

  14. Synchrotron Radiation and Energy Dispersive X-Ray Fluorescence Applications on Elemental Distribution in Human Hair and Bones

    NASA Astrophysics Data System (ADS)

    Carvalho, M. L.; Marques, A. F.; Brito, J.

    2003-01-01

    This work is an application of synchrotron microprobe X- Ray fluorescence in order to study elemental distribution along human hair samples of contemporary citizens. Furthermore, X-Ray fluorescence spectrometry is also used to analyse human bones of different historical periods: Neolithic and contemporary subjects. The elemental content in the bones allowed us to conclude about environmental contamination, dietary habits and health status influence in the corresponding citizens. All samples were collected post-mortem. Quantitative analysis was performed for Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr and Pb. Mn and Fe concentration were much higher in bones from pre-historic periods. On the contrary, Pb bone concentrations of contemporary subjects are much higher than in pre-historical ones, reaching 100 μg g-1, in some cases. Very low concentrations for Co, Ni, Br and Rb were found in all the analysed samples. Cu concentrations, allows to distinguish Chalcolithic bones from the Neolithic ones. The distribution of trace elements along human hair was studied for Pb and the obtained pattern was consistent with the theoretical model, based on the diffusion of this element from the root and along the hair. Therefore, the higher concentrations in hair for Pb of contemporary individuals were also observed in the bones of citizens of the same sampling sites. All samples were analysed directly without any chemical treatment.

  15. Mobile Applications for Diabetes Self-Management: Status and Potential

    PubMed Central

    El-Gayar, Omar; Timsina, Prem; Nawar, Nevine; Eid, Wael

    2013-01-01

    Background Advancements in smartphone technology coupled with the proliferation of data connectivity has resulted in increased interest and unprecedented growth in mobile applications for diabetes self-management. The objective of this article is to determine, in a systematic review, whether diabetes applications have been helping patients with type 1 or type 2 diabetes self-manage their condition and to identify issues necessary for large-scale adoption of such interventions. Methods The review covers commercial applications available on the Apple App Store (as a representative of commercially available applications) and articles published in relevant databases covering a period from January 1995 to August 2012. The review included all applications supporting any diabetes self-management task where the patient is the primary actor. Results Available applications support self-management tasks such as physical exercise, insulin dosage or medication, blood glucose testing, and diet. Other support tasks considered include decision support, notification/alert, tagging of input data, and integration with social media. The review points to the potential for mobile applications to have a positive impact on diabetes self-management. Analysis indicates that application usage is associated with improved attitudes favorable to diabetes self-management. Limitations of the applications include lack of personalized feedback; usability issues, particularly the ease of data entry; and integration with patients and electronic health records. Conclusions Research into the adoption and use of user-centered and sociotechnical design principles is needed to improve usability, perceived usefulness, and, ultimately, adoption of the technology. Proliferation and efficacy of interventions involving mobile applications will benefit from a holistic approach that takes into account patients’ expectations and providers’ needs. PMID:23439183

  16. Potential National Security Applications of Nuclear Resonance Fluorescence Methods

    SciTech Connect

    Warren, Glen A.; Peplowski, Patrick N.; Caggiano, Joseph A.

    2009-06-09

    The objective of this report is to document the initial investigation into the possible research issues related to the development of NRF-based national security applications. The report discusses several potential applications ranging from measuring uranium enrichment in UF6 canisters to characterization of gas samples. While these applications are varied, there are only a few research issues that need to be addressed to understand the limitation of NRF in solving these problems. These research issues range from source and detector development to measuring small samples. The next effort is to determine how best to answer the research issues, followed by a prioritization of those questions to ensure that the most important are addressed. These issues will be addressed through either analytical calculations, computer simulations, analysis of previous data or collection of new measurements. It will also be beneficial to conduct a thorough examination of a couple of the more promising applications in order to develop concrete examples of how NRF may be applied in specific situations. The goals are to develop an understanding of whether the application of NRF is limited by technology or physics in addressing national security applications, to gain a motivation to explore those possible applications, and to develop a research roadmap so that those possibilities may be made reality.

  17. Application of Autologous Bone Marrow Derived Mesenchymal Stem Cells to an Ovine Model of Growth Plate Cartilage Injury

    PubMed Central

    McCarty, Rosa C; Xian, Cory J; Gronthos, Stan; Zannettino, Andrew C.W; Foster, Bruce K

    2010-01-01

    Injury to growth plate cartilage in children can lead to bone bridge formation and result in bone growth deformities, a significant clinical problem currently lacking biological treatment. Mesenchymal stem/stromal cells (MSC) offer a promising therapeutic option for regeneration of damaged cartilage, due to their self renewing and multi-lineage differentiation attributes. Although some small animal model studies highlight the therapeutic potential of MSC for growth plate repair, translational research in large animal models, which more closely resemble the human condition, are lacking. Our laboratory has recently characterised MSCs derived from ovine bone marrow, and demonstrated these cells form cartilage-like tissue when transplanted within the gelatin sponge, Gelfoam, in vivo. In the current study, autologous bone marrow MSC were seeded into Gelfoam scaffold containing TGF-β1, and transplanted into a surgically created defect of the proximal ovine tibial growth plate. Examination of implants at 5 week post-operatively revealed transplanted autologous MSC failed to form new cartilage structure at the defect site, but contributed to an increase in formation of a dense fibrous tissue. Importantly, the extent of osteogenesis was diminished, and bone bridge formation was not accelerated due to transplantation of MSCs or the gelatin scaffold. The current study represents the first work that has utilised this ovine large animal model to investigate whether autologous bone marrow derived MSC can be used to initiate regeneration at the injured growth plate. PMID:20721323

  18. Thermophilic and alkaliphilic Actinobacteria: biology and potential applications

    PubMed Central

    Shivlata, L.; Satyanarayana, Tulasi

    2015-01-01

    Microbes belonging to the phylum Actinobacteria are prolific sources of antibiotics, clinically useful bioactive compounds and industrially important enzymes. The focus of the current review is on the diversity and potential applications of thermophilic and alkaliphilic actinobacteria, which are highly diverse in their taxonomy and morphology with a variety of adaptations for surviving and thriving in hostile environments. The specific metabolic pathways in these actinobacteria are activated for elaborating pharmaceutically, agriculturally, and biotechnologically relevant biomolecules/bioactive compounds, which find multifarious applications. PMID:26441937

  19. Production of Chitooligosaccharides and Their Potential Applications in Medicine

    PubMed Central

    Aam, Berit B.; Heggset, Ellinor B.; Norberg, Anne Line; Sørlie, Morten; Vårum, Kjell M.; Eijsink, Vincent G. H.

    2010-01-01

    Chitooligosaccharides (CHOS) are homo- or heterooligomers of N-acetylglucosamine and D-glucosamine. CHOS can be produced using chitin or chitosan as a starting material, using enzymatic conversions, chemical methods or combinations thereof. Production of well-defined CHOS-mixtures, or even pure CHOS, is of great interest since these oligosaccharides are thought to have several interesting bioactivities. Understanding the mechanisms underlying these bioactivities is of major importance. However, so far in-depth knowledge on the mode-of-action of CHOS is scarce, one major reason being that most published studies are done with badly characterized heterogeneous mixtures of CHOS. Production of CHOS that are well-defined in terms of length, degree of N-acetylation, and sequence is not straightforward. Here we provide an overview of techniques that may be used to produce and characterize reasonably well-defined CHOS fractions. We also present possible medical applications of CHOS, including tumor growth inhibition and inhibition of TH2-induced inflammation in asthma, as well as use as a bone-strengthener in osteoporosis, a vector for gene delivery, an antibacterial agent, an antifungal agent, an anti-malaria agent, or a hemostatic agent in wound-dressings. By using well-defined CHOS-mixtures it will become possible to obtain a better understanding of the mechanisms underlying these bioactivities. PMID:20559485

  20. A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

    NASA Astrophysics Data System (ADS)

    Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O’Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

    2017-04-01

    Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83–105 Gy), whilst a median of 183 Gy (interquartile range: 107–247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

  1. A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

    PubMed

    Denis-Bacelar, Ana M; Chittenden, Sarah J; Murray, Iain; Divoli, Antigoni; Ralph McCready, V; Dearnaley, David P; O'Sullivan, Joe M; Johnson, Bernadette; Flux, Glenn D

    2017-04-07

    Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

  2. Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

    PubMed Central

    Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

    2012-01-01

    There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

  3. Introduction to nanotechnology: potential applications in physical medicine and rehabilitation.

    PubMed

    Gordon, Assaf T; Lutz, Greg E; Boninger, Michael L; Cooper, Rory A

    2007-03-01

    Nanotechnology is a scientific movement that has the potential to transform the diagnosis and treatment of disease in the 21st century. The area of investigation is defined by the study, design, manipulation, manufacture, and control of materials or devices by physical or chemical means at resolutions on the order of one billionth of a meter. The potential for a wide range of clinical applications makes a basic understanding of nanotechnology important to physiatrists. This review presents an introduction to nanotechnology and discusses key developments in tissue engineering, drug delivery, imaging, diagnostics, surface texturing, and biointerfaces that could impact the practice of physiatry in the future.

  4. The natural flavonoid pinocembrin: molecular targets and potential therapeutic applications

    PubMed Central

    Lan, Xi; Wang, Wenzhu; Li, Qiang; Wang, Jian

    2015-01-01

    Pinocembrin is a natural flavonoid compound extracted from honey, propolis, ginger roots, wild marjoram, and other plants. In preclinical studies, it has shown anti-inflammatory and neuroprotective effects as well as the ability to reduce reactive oxygen species, protect the blood-brain barrier, modulate mitochondrial function, and regulate apoptosis. Considering these pharmaceutical characteristics, pinocembrin has potential as a drug to treat ischemic stroke and other clinical conditions. In this review, we summarize its pharmacologic characteristics and discuss its mechanisms of action and potential therapeutic applications. PMID:25744566

  5. Neurotrophic Factors and Their Potential Applications in Tissue Regeneration.

    PubMed

    Xiao, Nan; Le, Quynh-Thu

    2016-04-01

    Neurotrophic factors are growth factors that can nourish neurons and promote neuron survival and regeneration. They have been studied as potential drug candidates for treating neurodegenerative diseases. Since their identification, there are more and more evidences to indicate that neurotrophic factors are also expressed in non-neuronal tissues and regulate the survival, anti-inflammation, proliferation and differentiation in these tissues. This mini review summarizes the characteristics of the neurotrophic factors and their potential clinical applications in the regeneration of neuronal and non-neuronal tissues.

  6. Neurotrophic Factors and Their Potential Applications in Tissue Regeneration

    PubMed Central

    Le, Quynh-Thu

    2016-01-01

    Neurotrophic factors are growth factors that can nourish neurons and promote neuron survival and regeneration. They have been studied as potential drug candidates for treating neurodegenerative diseases. Since their identification, there are more and more evidences to indicate that neurotrophic factors are also expressed in non-neuronal tissues and regulate the survival, anti-inflammation, proliferation and differentiation in these tissues. This mini review summarizes the characteristics of the neurotrophic factors and their potential clinical applications in the regeneration of neuronal and non-neuronal tissues. PMID:26611762

  7. Growth and Potential Damage of Human Bone-Derived Cells on Fresh and Aged Fullerene C60 Films

    PubMed Central

    Kopova, Ivana; Bacakova, Lucie; Lavrentiev, Vasily; Vacik, Jiri

    2013-01-01

    Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only able to quench, but also to generate harmful reactive oxygen species. The reactivity of fullerenes may change in time due to the oxidation and polymerization of fullerenes in an air atmosphere. In this study, we therefore tested the dependence between the age of fullerene films (from one week to one year) and the proliferation, viability and metabolic activity of human osteosarcoma cells (lines MG-63 and U-2 OS). We also monitored potential membrane and DNA damage and morphological changes of the cells. After seven days of cultivation, we did not observe any cytotoxic morphological changes, such as enlarged cells or cytosolic vacuole formation. Furthermore, there was no increased level of DNA damage. The increasing age of the fullerene films did not cause enhancement of cytotoxicity. On the contrary, it resulted in an improvement in the properties of these materials, which are more suitable for cell cultivation. Therefore, fullerene films could be considered as a promising material with potential use as a bioactive coating of cell carriers for bone tissue engineering. PMID:23624607

  8. Potential applications of immunoassays in studies of flatfish recruitment

    NASA Astrophysics Data System (ADS)

    Feller, Robert J.

    The fisheries recruitment-stock problem, a lack of correlation between measures of reproductive output of the parent stock and recruitment to the fishery, has several potential biotic and abiotic causes. Immunoassays may be useful in examining several aspects of this and several other problems in flatfish ecology: stock identification, parasitism and disease, and trophic interactions. Given stage-specific antisera capable of recognozing antigenic moieties of, for instance, eggs, larvae, or newly-settled juveniles, it is possible to screen stomach contents of many putative predators ( e.g., shrimp or crabs) rapidly for the presence and amounts of platfish prey. This trophic application of immunological methods has great promise for measuring loss of potential recruits to predation. All immunoassays are limited by the quality of antisera used and the researcher's ability to interpret quantitative data in an ecologically meaningful way. Key references for applications of immunoassays in fish-related questions are provided with recommendations for their utilization.

  9. Bacterial quorum sensing: functional features and potential applications in biotechnology.

    PubMed

    Mangwani, Neelam; Dash, Hirak Ranjan; Chauhan, Ashvini; Das, Surajit

    2012-01-01

    Quorum sensing (QS) represents an exceptional pattern of cell-to-cell communication in bacteria using self-synthesized signalling molecules known as autoinducers. Various features regulated by QS in bacteria include virulence, biofilm formation, sporulation, genetic competence and bioluminescence, among others. Other than the diverse signalling properties of autoinducers, there are non-signalling properties also associated with these signalling molecules which make them potential antimicrobial agents and metal chelators. Additionally, QS signal antagonism has also been shown to be a promising alternative for blocking pathogenic diseases. Besides, QS has impressive design features useful in tissue engineering and biosensor technology. Although many aspects of QS are well understood, several other features remain largely unknown, especially in biotechnology applications. This review focuses on the functional features and potential applications of QS signalling molecules in biotechnology.

  10. Molecular sonography with targeted microbubbles: current investigations and potential applications.

    PubMed

    Hwang, Misun; Lyshchik, Andrej; Fleischer, Arthur C

    2010-06-01

    Sonography using targeted microbubbles affords a variety of diagnostic and potentially therapeutic clinical applications. It provides a whole new world of functional information at the cellular and molecular level. This information can then be used to diagnose and possibly prevent diseases at early stages as well as devise therapeutic strategies at the molecular level. It is also useful in monitoring tumor response to therapy and devising treatment timing and plans based on the molecular state of an individual's health. Moreover, targeted microbubble-enhanced sonography has several advantages over other imaging modalities, including widespread availability, low cost, fast acquisition times, and lack of radiation risk. These traits are likely to advance it as one of the imaging methods of choice in future clinical trials examining the impact of molecular imaging on treatment outcome. This review describes the fundamental concepts of targeted microbubble-enhanced sonography as well as its potential clinical applications.

  11. Enhancement of the Regenerative Potential of Anorganic Bovine Bone Graft Utilizing a Polyglutamate-Modified BMP2 Peptide with Improved Binding to Calcium-Containing Materials

    PubMed Central

    Bain, Jennifer L.; Bonvallet, Paul P.; Abou-Arraj, Ramzi V.; Schupbach, Peter

    2015-01-01

    Autogenous bone is the gold standard material for bone grafting in craniofacial and orthopedic regenerative medicine. However, due to complications associated with harvesting donor bone, clinicians often use commercial graft materials that may lose their osteoinductivity due to processing. This study was aimed to functionalize one of these materials, anorganic bovine bone (ABB), with osteoinductive peptides to enhance regenerative capacity. Two peptides known to induce osteoblastic differentiation of mesenchymal stem cells were evaluated: (1) DGEA, an amino acid motif within collagen I and (2) a biomimetic peptide derived from bone morphogenic protein 2 (BMP2pep). To achieve directed coupling of the peptides to the graft surface, the peptides were engineered with a heptaglutamate domain (E7), which confers specific binding to calcium moieties within bone mineral. Peptides with the E7 domain exhibited greater anchoring to ABB than unmodified peptides, and E7 peptides were retained on ABB for at least 8 weeks in vivo. To assess the osteoinductive potential of the peptide-conjugated ABB, ectopic bone formation was evaluated utilizing a rat subcutaneous pouch model. ABB conjugated with full-length recombinant BMP2 (rBMP2) was also implanted as a model for current clinical treatments utilizing rBMP2 passively adsorbed to carriers. These studies showed that E7BMP2pep/ABB samples induced more new bone formation than all other peptides, and an equivalent amount of new bone as compared with rBMP2/ABB. A mandibular defect model was also used to examine intrabony healing of peptide-conjugated ABB. Bone healing was monitored at varying time points by positron emission tomography imaging with 18F-NaF, and it was found that the E7BMP2pep/ABB group had greater bone metabolic activity than all other groups, including rBMP2/ABB. Importantly, animals implanted with rBMP2/ABB exhibited complications, including inflammation and formation of cataract-like lesions in the eye, whereas no

  12. 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

  13. Potential applications of nanostructured materials in nuclear waste management.

    SciTech Connect

    Braterman, Paul S. (The University of North Texas, Denton, TX); Phol, Phillip Isabio; Xu, Zhi-Ping (The University of North Texas, Denton, TX); Brinker, C. Jeffrey; Yang, Yi; Bryan, Charles R.; Yu, Kui; Xu, Huifang (University of New Mexico, Albuquerque, NM); Wang, Yifeng; Gao, Huizhen

    2003-09-01

    This report summarizes the results obtained from a Laboratory Directed Research & Development (LDRD) project entitled 'Investigation of Potential Applications of Self-Assembled Nanostructured Materials in Nuclear Waste Management'. The objectives of this project are to (1) provide a mechanistic understanding of the control of nanometer-scale structures on the ion sorption capability of materials and (2) develop appropriate engineering approaches to improving material properties based on such an understanding.

  14. Phytases: crystal structures, protein engineering and potential biotechnological applications.

    PubMed

    Yao, M-Z; Zhang, Y-H; Lu, W-L; Hu, M-Q; Wang, W; Liang, A-H

    2012-01-01

    Phytases are a group of enzymes capable of releasing phosphates from phytates, one of the major forms of phosphorus (P) in animal feeds of plant origin. These enzymes have been widely used in animal feed to improve phosphorus nutrition and to reduce phosphorus pollution in animal waste. This review covers the basic nomenclature and crystal structures of phytases and emphasizes both the protein engineering strategies used for the development of new, effective phytases with improved properties and the potential biotechnological applications of phytases.

  15. Potential impacts of nanotechnology on energy transmission applications and needs.

    SciTech Connect

    Elcock, D.; Environmental Science Division

    2007-11-30

    The application of nanotechnologies to energy transmission has the potential to significantly impact both the deployed transmission technologies and the need for additional development. This could be a factor in assessing environmental impacts of right-of-way (ROW) development and use. For example, some nanotechnology applications may produce materials (e.g., cables) that are much stronger per unit volume than existing materials, enabling reduced footprints for construction and maintenance of electricity transmission lines. Other applications, such as more efficient lighting, lighter-weight materials for vehicle construction, and smaller batteries having greater storage capacities may reduce the need for long-distance transport of energy, and possibly reduce the need for extensive future ROW development and many attendant environmental impacts. This report introduces the field of nanotechnology, describes some of the ways in which processes and products developed with or incorporating nanomaterials differ from traditional processes and products, and identifies some examples of how nanotechnology may be used to reduce potential ROW impacts. Potential environmental, safety, and health impacts are also discussed.

  16. Potential applications of bioprocess technology in petroleum industry.

    PubMed

    Singh, Ajay; Singh, Brajesh; Ward, Owen

    2012-11-01

    Petroleum refining is traditionally based on the use of physicochemical processes such as distillation and chemical catalysis that operate under high temperatures and pressures conditions, which are energy intensive and costly. Biotechnology has become an important tool for providing new approaches in petroleum industry during oil production, refining and processing as well as managing environmentally safe pollutant remediation and disposal practices. Earlier biotechnology applications in the petroleum industry were limited to microbial enhanced oil recovery, applications of bioremediation to contaminated marine shorelines, soils and sludges. The potential role of bioprocess technology in this industry has now expanded further into the areas of biorefining and upgrading of fuels, production of fine chemicals, control of souring during production and air VOC biofiltration. In this paper we provide an overview of the major applications of bioprocesses and technology development in the petroleum industry both in upstream and downstream areas and highlight future challenges and opportunities.

  17. Solar energy in California industry - Applications, characteristics and potential

    NASA Technical Reports Server (NTRS)

    Barbieri, R. H.; Pivirotto, D. S.

    1978-01-01

    Results of a survey to determine the potential applicability of solar thermal energy to industrial processes in California are presented. It is found that if the heat for all industrial processes at temperatures below 212 F were supplied by solar energy, total state energy consumption could be reduced by 100 trillion Btus (2%), while the use of solar energy in processes between 212 and 350 F could displace 500 trillion Btus. The issues and problems with which solar energy must contend are illustrated by a description of fluid milk processing operations. Solar energy application is found to be technically feasible for processes with thermal energy requirements below 212 F, with design, and degree of technical, economic and management feasibility being site specific. It is recommended that the state provide support for federal and industrial research, development and demonstration programs in order to stimulate acceptance of solar process heat application by industry.

  18. MicroRNAs as potential target in human bone and soft tissue sarcoma therapeutics

    PubMed Central

    Varshney, Jyotika; Subramanian, Subbaya

    2015-01-01

    Sarcomas are highly aggressive heterogeneous tumors that are mesenchymal in origin. There have been vast advancements on identifying diagnostic markers for sarcomas including chromosomal translocations, but very little progress has been made to identify targeted therapies against them. The tumor heterogeneity, genetic complexity and the lack of drug studies make it challenging to recognize the potential targets and also accounts for the inadequate treatments in sarcomas. In recent years, microRNAs that are a part of small non-coding RNAs have shown promising results as potential diagnostic and prognostic biomarkers in multiple sarcoma types. This review focuses on the current knowledge of the microRNAs that are deregulated in sarcomas, and an insight on the strategies to target these microRNAs that are essential for developing improved therapies for various human sarcomas. PMID:26137468

  19. [The application of osteoscintigraphy in forensic medical practice for the detection and differentiation of bone fractures in the living human].

    PubMed

    Gusarov, A A; Fetisov, V A; Kuprina, T A

    2016-01-01

    This paper is designed to present an example from the domestic expert practice with the successful application of the radionuclide technique to visualize the bone lesions in a victim of a traffic accident having concomitant pathology of the osseous-articular apparatus (Scheuermann-Mau disease). The use of the osteoscintigraphic method made it possible not only to confirm the injury to the spinal column and the sternum but also to ensure its differential diagnostics from the concurrent pathology. Also, the method allowed to detect the exact location of the fractures. Moreover, it proved possible to comprehensively characterize the mechanism underlying the bone fracture resulting from the car accident.

  20. Potentials and problems in space applications of smart structures technology

    NASA Astrophysics Data System (ADS)

    Eaton, D. C.; Bashford, D. P.

    1994-09-01

    The well known addage 'don't run before you can walk emerging materials. It typically takes ten years before a material is sufficiently well characterized for commercial aerospace application. Much has to be learnt not only about the material properties and their susceptibility to the effects of their working environment but also about the manufacturing process and the most effective configuration related application. No project will accept a product which has no proven reliability and attractive cost effectiveness in its application. The writers firmly believe that smart structures and their related technologies must follow a similar development pattern. Indeed, faced with a range of interdisciplinary problems it seems likely that 'partially smart' techniques may well be the first applications. These will place emphasis on the more readily realizable features for any structural application. Prior use may well have been achieved in other engineering sectors. Because ground based applications are more readily accessible to check and maintain, these are generally the front runners of smart technology usage. Nevertheless, there is a strong potential for the use of smart techniques in space applications if their capabilities can be advantageously introduced when compared with traditional solutions. This paper endeavors to give a critical appraisal of the possibilities and the accompanying problems. A sample overview of related developing space technology is included. The reader is also referred to chapters 90 to 94 in ESA's Structural Materials Handbook (ESA PSS 03 203, issue 1.). It is envisaged that future space applications may include the realization and maintenance of large deployable reflector profiles, the dimensional stability of optical payloads, active noise and vibration control and in orbit health monitoring and control for largely unmanned spacecraft. The possibility of monitoring the health of items such as large cryogenic fuel tanks is a typical longer

  1. Statistical shape and appearance models of bones.

    PubMed

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

    2014-03-01

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

  2. Bone ingrowth potential of electron beam and selective laser melting produced trabecular-like implant surfaces with and without a biomimetic coating.

    PubMed

    Biemond, J E; Hannink, G; Verdonschot, N; Buma, P

    2013-03-01

    The bone ingrowth potential of trabecular-like implant surfaces produced by either selective laser melting (SLM) or electron beam melting (EBM), with or without a biomimetic calciumphosphate coating, was examined in goats. For histological analysis and histomorphometry of bone ingrowth depth and bone implant contact specimens were implanted in the femoral condyle of goats. For mechanical push out tests to analyse mechanical implant fixation specimens were implanted in the iliac crest. The follow up periods were 4 (7 goats) and 15 weeks (7 goats). Both the SLM and EBM produced trabecular-like structures showed a variable bone ingrowth after 4 weeks. After 15 weeks good bone ingrowth was found in both implant types. Irrespective to the follow up period, and the presence of a coating, no histological differences in tissue reaction around SLM and EBM produced specimens was found. Histological no coating was detected at 4 and 15 weeks follow up. At both follow up periods the mechanical push out strength at the bone implant interface was significantly lower for the coated SLM specimens compared to the uncoated SLM specimens. The expected better ingrowth characteristics and mechanical fixation strength induced by the coating were not found. The lower mechanical strength of the coated specimens produced by SLM is a remarkable result, which might be influenced by the gross morphology of the specimens or the coating characteristics, indicating that further research is necessary.

  3. Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

    PubMed Central

    Yuan, Tong-ling; Chen, Jin; Tong, Yan-li; Zhang, Yan; Liu, Yuan-yuan; Wei, James Cheng-Chung; Liu, Yi; Herrmann, Martin

    2016-01-01

    Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p < 0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p < 0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p < 0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p < 0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis. PMID:27314037

  4. Bioactive Glass Fiber Reinforced Starch-Polycaprolactone Composite for Bone Applications

    NASA Astrophysics Data System (ADS)

    Jukola, H.; Nikkola, L.; Gomes, M. E.; Chiellini, F.; Tukiainen, M.; Kellomäki, M.; Chiellini, E.; Reis, R. L.; Ashammakhi, N.

    2008-02-01

    For bone regeneration and repair, combinations of different materials are often needed. Biodegradable polymers are often combined with osteoconductive materials, such as bioactive glass (BaG), which can also improve the mechanical properties of the composite. The aim of this study was to develop and characterize BaG fiber-reinforced starch-poly-ɛ-caprolactone (SPCL) composite. Sheets of SPCL (30/70 wt%) were produced using single-screw extrusion. They were then cut and compression molded in layers with BaG fibers to form composite structures of different combinations. Thermal, mechanical, and degradation properties of the composites were studied. The actual amount of BaG in the composites was determined using combustion tests. A strong endothermic peak indicating melting at about 56 °C was observed by differential scanning calorimetry (DSC) analysis. Thermal gravimetry analysis (TGA) showed that thermal decomposition of SPCL started at 325 °C with the decomposition of starch and continued at 400 °C with the degradation of polycaprolactone (PCL). Initial mechanical properties of the reinforced composites were at least 50% better than the properties of the non-reinforced composites. However, the mechanical properties of the composites after two weeks of hydrolysis were comparable to those of the non-reinforced samples. During the six weeks' hydrolysis the mass of the composites had decreased only by about 5%. The amount of glass in the composites remained the same for the six-week period of hydrolysis. In conclusion, it is possible to enhance the initial mechanical properties of SPCL by reinforcing it with BaG fibers. However, the mechanical properties of the composites are only sufficient for use as filler material and they need to be further improved to allow long-lasting bone applications.

  5. Bioactive Glass Fiber Reinforced Starch-Polycaprolactone Composite for Bone Applications

    SciTech Connect

    Jukola, H.; Nikkola, L.; Tukiainen, M.; Kellomaeki, M.; Ashammakhi, N.; Gomes, M. E.; Reis, R. L.; Chiellini, F.; Chiellini, E.

    2008-02-15

    For bone regeneration and repair, combinations of different materials are often needed. Biodegradable polymers are often combined with osteoconductive materials, such as bioactive glass (BaG), which can also improve the mechanical properties of the composite. The aim of this study was to develop and characterize BaG fiber-reinforced starch-poly-{epsilon}-caprolactone (SPCL) composite. Sheets of SPCL (30/70 wt%) were produced using single-screw extrusion. They were then cut and compression molded in layers with BaG fibers to form composite structures of different combinations. Thermal, mechanical, and degradation properties of the composites were studied. The actual amount of BaG in the composites was determined using combustion tests. A strong endothermic peak indicating melting at about 56 deg. C was observed by differential scanning calorimetry (DSC) analysis. Thermal gravimetry analysis (TGA) showed that thermal decomposition of SPCL started at 325 deg. C with the decomposition of starch and continued at 400 deg. C with the degradation of polycaprolactone (PCL). Initial mechanical properties of the reinforced composites were at least 50% better than the properties of the non-reinforced composites. However, the mechanical properties of the composites after two weeks of hydrolysis were comparable to those of the non-reinforced samples. During the six weeks' hydrolysis the mass of the composites had decreased only by about 5%. The amount of glass in the composites remained the same for the six-week period of hydrolysis. In conclusion, it is possible to enhance the initial mechanical properties of SPCL by reinforcing it with BaG fibers. However, the mechanical properties of the composites are only sufficient for use as filler material and they need to be further improved to allow long-lasting bone applications.

  6. Application of mesenchymal stem cells in bone regenerative procedures in oral implantology. A literature review

    PubMed Central

    Viña, Jose A.; El-Alami, Marya; Gambini, Juan; Borras, Consuelo; Viña, Jose

    2014-01-01

    Objective: The aim of this work was to review de literature about the role of mesenchymal stem cells in bone regenerative procedures in oral implantology, specifically, in the time require to promote bone regeneration. Study Design: A bibliographic search was carried out in PUBMED with a combination of different key words. Animal and human studies that assessed histomorphometrically the influence of mesenchymal stem cells on bone regeneration procedures in oral implantology surgeries were examined. Reults: - Alveolar regeneration: Different controlled histomorphometric animal studies showed that bone regeneration is faster using stem cells seeded in scaffolds than using scaffolds or platelet rich plasma alone. Human studies revealed that stem cells increase bone regeneration. - Maxillary sinus lift: Controlled studies in animals and in humans showed higher bone regeneration applying stem cells compared with controls. - Periimplantary bone regeneration and alveolar distraction: Studies in animals showed higher regeneration when stem cells are used. In humans, no evidence of applying mesenchymal stem cells in these regeneration procedures was found. Conclusion: Stem cells may promote bone regeneration and be useful in bone regenerative procedures in oral implantology, but no firm conclusions can be drawn from the rather limited clinical studies so far performed. Key words:Mesenchymal stem cells, bone regeneration, dental implants, oral surgery, tissue engineering. PMID:24596637

  7. Histological evaluation of the influence of magnetic field application in autogenous bone grafts in rats

    PubMed Central

    Puricelli, Edela; Dutra, Nardier B; Ponzoni, Deise

    2009-01-01

    Background Bone grafts are widely used in oral and maxillofacial reconstruction. The influence of electromagnetic fields and magnets on the endogenous stimulation of target tissues has been investigated. This work aimed to assess the quality of bone healing in surgical cavities filled with autogenous bone grafts, under the influence of a permanent magnetic field produced by in vivo buried devices. Methods Metal devices consisting of commercially pure martensitic stainless steel washers and titanium screws were employed. Thirty male Wistar rats were divided into 3 experimental and 3 control groups. A surgical bone cavity was produced on the right femur, and a bone graft was collected and placed in each hole. Two metallic washers, magnetized in the experimental group but not in the control group, were attached on the borders of the cavity. Results The animals were sacrificed on postoperative days 15, 45 and 60. The histological analysis of control and experimental samples showed adequate integration of the bone grafts, with intense bone neoformation. On days 45 and 60, a continued influence of the magnetic field on the surgical cavity and on the bone graft was observed in samples from the experimental group. Conclusion The results showed intense bone neoformation in the experimental group as compared to control animals. The intense extra-cortical bone neoformation observed suggests that the osteoconductor condition of the graft may be more susceptible to stimulation, when submitted to a magnetic field. PMID:19134221

  8. Potential Applications of Smart Multifunctional Wearable Materials to Gerontology.

    PubMed

    Armstrong, David G; Najafi, Bijan; Shahinpoor, Mohsen

    2017-01-12

    Smart multifunctional materials can play a constructive role in addressing some very important aging-related issues. Aging affects the ability of older adults to continue to live safely and economically in their own residences for as long as possible. Thus, there will be a greater need for preventive, acute, rehabilitative, and long-term health care services for older adults as well as a need for tools to enable them to function independently during daily activities. The objective of this paper is, thus, to present a comprehensive review of some potential smart materials and their areas of applications to gerontology. Thus, brief descriptions of various currently available multifunctional smart materials and their possible applications to aging-related problems are presented. It is concluded that some of the most important applications to geriatrics may be in various sensing scenarios to collect health-related feedback or information and provide personalized care. Further described are the applications of wearable technologies to aging-related needs, including devices for home rehabilitation, remote monitoring, social well-being, frailty monitoring, monitoring of diabetes and wound healing and fall detection or prediction. It is also concluded that wearable technologies, when combined with an appropriate application and with appropriate feedback, may help improve activities and functions of older patients with chronic diseases. Finally, it is noted that methods developed to measure what one collectively manages in this population may provide a foundation to establish new definitions of quality of life.

  9. Space simulations of thermal fields generated in bone tissue for application to nanophotohyperthermia and nanophotothermolysis

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    The use of nanoparticles in medical applications has been gaining momentum as antibody-conjugated nanoparticles are becoming more and more feasible as a means of targeted delivery of various therapies. Irradiating nanoparticles with light of strongly-absorbed wavelengths allows them to act as heat generation sites. Two therapies utilize these nanoparticle heat sources to kill the target cells: nanophotohyperthermia, which heats the particles just enough to disrupt cell function and trigger cell death; and nanophotothermolysis, which heats the particles to such extremes as to destroy the cell membrane. The use of optical wavelengths in the range of 750-1100 nm has been to capitalize on the "optical transparency window" of biotissues between the absorption peaks of hemoglobin in the visible end and water in the near-IR. However, further research has shown that a plasmon resonance can greatly affect the absorption characteristics of nanoparticles at the plasmon resonant frequency, allowing for increased absorption characteristics at desirable wavelengths. Thus, other transparency windows may find use in a similar manner, such as nanoparticle heating by RF waves. This paper presents the modeling of 3D thermal fields around nanoparticle absorbers in bone tissue for various frequencies. A comparison of the heating effectiveness across multiple wavelengths is discussed for application to nanophotothermolysis and nanophotohyperthermia treatments in or near biological hard tissue.

  10. Dexamethasone Regulates EphA5, a Potential Inhibitory Factor with Osteogenic Capability of Human Bone Marrow Stromal Cells

    PubMed Central

    Yamada, Tsuyoshi; Yoshii, Toshitaka; Yasuda, Hiroaki; Okawa, Atsushi; Sotome, Shinichi

    2016-01-01

    We previously demonstrated the importance of quality management procedures for the handling of human bone marrow stromal cells (hBMSCs) and provided evidence for the existence of osteogenic inhibitor molecules in BMSCs. One candidate inhibitor is the ephrin type-A receptor 5 (EphA5), which is expressed in hBMSCs and upregulated during long-term culture. In this study, forced expression of EphA5 diminished the expression of osteoblast phenotypic markers. Downregulation of endogenous EphA5 by dexamethasone treatment promoted osteoblast marker expression. EphA5 could be involved in the normal growth regulation of BMSCs and could be a potential marker for replicative senescence. Although Eph forward signaling stimulated by ephrin-B-Fc promoted the expression of ALP mRNA in BMSCs, exogenous addition of EphA5-Fc did not affect the ALP level. The mechanism underlying the silencing of EphA5 in early cultures remains unclear. EphA5 promoter was barely methylated in hBMSCs while histone deacetylation could partially suppress EphA5 expression in early-passage cultures. In repeatedly passaged cultures, the upregulation of EphA5 independent of methylation could competitively inhibit osteogenic signal transduction pathways such as EphB forward signaling. Elucidation of the potential inhibitory function of EphA5 in hBMSCs may provide an alternative approach for lineage differentiation in cell therapy strategies and regenerative medicine. PMID:27057165

  11. Radionuclide bone imaging and densitometry

    SciTech Connect

    Mettler, F.A.

    1988-01-01

    This book contains 13 selections. Some of the titles are: Radionuclides and the Normal Bone Scan; The Radionuclide Bone Scan in Malignant Disease; Pediatric Applications of Radionuclide Bone Imaging; The Radionuclide Bone Scan in Arthritis and Metabolic and Miscellaneous Disorders; and Soft Tissue Activity on the Radionuclide Bone Scan.

  12. Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications

    NASA Astrophysics Data System (ADS)

    Moretti, Pierre; Hatlapatka, Tim; Marten, Dana; Lavrentieva, Antonina; Majore, Ingrida; Hass, Ralf; Kasper, Cornelia

    Mesenchymal stem or stromal cells (MSCs) have a high potential for cell-based therapies as well as for tissue engineering applications. Since Friedenstein first isolated stem or precursor cells from the human bone marrow (BM) stroma that were capable of osteogenesis, BM is currently the most common source for MSCs. However, BM presents several disadvantages, namely low frequency of MSCs, high donor-dependent variations in quality, and painful invasive intervention. Thus, tremendous research efforts have been observed during recent years to find alternative sources for MSCs.

  13. In vitro bioactivity assessment of composite membrane containing antimicrobial lauric acid for guided bone regeneration in dental application

    NASA Astrophysics Data System (ADS)

    Suleiman, Muhammad Jabir; Kalitheertha, Jamuna Thevi; Sabri, Siti Noorzidah

    2015-07-01

    The manuscript reflect research work in fabrication of a triple layered composite membrane and to perform an in vitro bioactivity evaluation on composite membrane containing antimicrobial lauric acid. Poly(lactic-co-glycolic acid) (PLGA) matrix was incorporated with various amounts of nanoapatite (NAp) and lauric acid (LA) to form a triple-layered composite membrane. This membrane was prepared using a single step fabrication technique comprising of solvent casting, thermally induced phase separation and solvent leaching processes. Apatite mineralization was detected on the composite membranes within 30 days of exposure to simulated body fluid (SBF) and showed increased apatite formation at 30-60wt% of NAp content in the PLGA matrix on layer 3 (L3), that has the highest amount of NAp compared with layer 1 (L1) and layer 2 (L2) of the membrane. However, apatite mineralization was not detected on pure PLGA membrane. In addition, incorporation of LA on L1 and L2 has no influence on apatite mineral formation as none detected on these surfaces. The presence of NAp determines the formation of apatite crystals on the composite membrane. These membranes with triple layered design and bioactive properties showed potential use for guided bone regeneration purposes in dental application.

  14. Application of the digital volume correlation technique for the measurement of displacement and strain fields in bone: a literature review.

    PubMed

    Roberts, Bryant C; Perilli, Egon; Reynolds, Karen J

    2014-03-21

    Digital volume correlation (DVC) provides experimental measurements of displacements and strains throughout the interior of porous materials such as trabecular bone. It can provide full-field continuum- and tissue-level measurements, desirable for validation of finite element models, by comparing image volumes from subsequent µCT scans of a sample in unloaded and loaded states. Since the first application of DVC for measurement of strain in bone tissue, subsequent reports of its application to trabecular bone cores up to whole bones have appeared within the literature. An "optimal" set of procedures capable of precise and accurate measurements of strain, however, still remains unclear, and a systematic review focussing explicitly on the increasing number of DVC algorithms applied to bone or structurally similar materials is currently unavailable. This review investigates the effects of individual parameters reported within individual studies, allowing to make recommendations for suggesting algorithms capable of achieving high accuracy and precision in displacement and strain measurements. These recommendations suggest use of subsets that are sufficiently large to encompass unique datasets (e.g. subsets of 500 µm edge length when applied to human trabecular bone cores, such as cores 10mm in height and 5mm in diameter, scanned at 15 µm voxel size), a shape function that uses full affine transformations (translation, rotation, normal strain and shear strain), the robust normalized cross-correlation coefficient objective function, and high-order interpolation schemes. As these employ computationally burdensome algorithms, researchers need to determine whether they have the necessary computational resources or time to adopt such strategies. As each algorithm is suitable for parallel programming however, the adoption of high precision techniques may become more prevalent in the future.

  15. Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

    SciTech Connect

    Lu, Li; Song, Hui-Fang; Zhang, Wei-Guo; Liu, Xue-Qin; Zhu, Qian; Cheng, Xiao-Long; Yang, Gui-Jiao; Li, Ang; Xiao, Zhi-Cheng

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer Prolonged culture expansion retards proliferation and induces senescence of hBMSCs. Black-Right-Pointing-Pointer Reduced 20S proteasomal activity and expression potentially contribute to cell aging. Black-Right-Pointing-Pointer MG132-mediated 20S proteasomal inhibition induces senescence-like phenotype. Black-Right-Pointing-Pointer 18{alpha}-GA stimulates proteasomal activity and restores replicative senescence. Black-Right-Pointing-Pointer 18{alpha}-GA retains differentiation without affecting stem cell characterizations. -- Abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18{alpha}-glycyrrhetinic acid (18{alpha}-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.

  16. Thermophotovoltaic potential applications for civilian and industrial use in Japan

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Hiromi; Yamaguchi, Masafumi

    1999-03-01

    Investigative research on potential market for TPV power sources in Japan has been focused on how TPV can contribute to energy conservation and environmental protection and harmony. The application needs for TPV were surveyed in comparison with conventional engine or turbine generators and developing power generation technologies such as fuel cells or chemical batteries, etc. The investigation on the performance of commercial generators shows that regarding system efficiency, TPV can compete with conventional generators in the output power class of tens of kW. According to the sales for small scale generators in Japan, most of the generators below 10 kW class are utilized mainly for construction, communication, leisure, and that 10-100 kW class generators are for cogeneration in small buildings. Waste heat recovery in dispersed furnaces is another potential application of compact TPV cells. Exhaust heat from small scale incinerators and industrial furnaces is undesirable to be recorded into electricity due to excessive heat loss of the smaller steam turbine generators. Solar powered TPV is also of our concern as a natural energy use. From the viewpoint of applicability for TPV, portable generators cogeneration systems, and solar power plants were selected for our system consideration. Intermediate report on the feasibility study concerning such TPV systems is given as well as the review of the current status of competing power generation technologies in Japan.

  17. Nanotechnology in meat processing and packaging: potential applications - a review.

    PubMed

    Ramachandraiah, Karna; Han, Sung Gu; Chin, Koo Bok

    2015-02-01

    Growing demand for sustainable production, increasing competition and consideration of health concerns have led the meat industries on a path to innovation. Meat industries across the world are focusing on the development of novel meat products and processes to meet consumer demand. Hence, a process innovation, like nanotechnology, can have a significant impact on the meat processing industry through the development of not only novel functional meat products, but also novel packaging for the products. The potential benefits of utilizing nanomaterials in food are improved bioavailability, antimicrobial effects, enhanced sensory acceptance and targeted delivery of bioactive compounds. However, challenges exist in the application of nanomaterials due to knowledge gaps in the production of ingredients such as nanopowders, stability of delivery systems in meat products and health risks caused by the same properties which also offer the benefits. For the success of nanotechnology in meat products, challenges in public acceptance, economics and the regulation of food processed with nanomaterials which may have the potential to persist, accumulate and lead to toxicity need to be addressed. So far, the most promising area for nanotechnology application seems to be in meat packaging, but the long term effects on human health and environment due to migration of the nanomaterials from the packaging needs to be studied further. The future of nanotechnology in meat products depends on the roles played by governments, regulatory agencies and manufacturers in addressing the challenges related to the application of nanomaterials in food.

  18. Potential biodefense model applications for portable chlorine dioxide gas production.

    PubMed

    Stubblefield, Jeannie M; Newsome, Anthony L

    2015-01-01

    Development of decontamination methods and strategies to address potential infectious disease outbreaks and bioterrorism events are pertinent to this nation's biodefense strategies and general biosecurity. Chlorine dioxide (ClO2) gas has a history of use as a decontamination agent in response to an act of bioterrorism. However, the more widespread use of ClO2 gas to meet current and unforeseen decontamination needs has been hampered because the gas is too unstable for shipment and must be prepared at the application site. Newer technology allows for easy, onsite gas generation without the need for dedicated equipment, electricity, water, or personnel with advanced training. In a laboratory model system, 2 unique applications (personal protective equipment [PPE] and animal skin) were investigated in the context of potential development of decontamination protocols. Such protocols could serve to reduce human exposure to bacteria in a decontamination response effort. Chlorine dioxide gas was capable of reducing (2-7 logs of vegetative and spore-forming bacteria), and in some instances eliminating, culturable bacteria from difficult to clean areas on PPE facepieces. The gas was effective in eliminating naturally occurring bacteria on animal skin and also on skin inoculated with Bacillus spores. The culturable bacteria, including Bacillus spores, were eliminated in a time- and dose-dependent manner. Results of these studies suggested portable, easily used ClO2 gas generation systems have excellent potential for protocol development to contribute to biodefense strategies and decontamination responses to infectious disease outbreaks or other biothreat events.

  19. Adaptive coded aperture imaging: progress and potential future applications

    NASA Astrophysics Data System (ADS)

    Gottesman, Stephen R.; Isser, Abraham; Gigioli, George W., Jr.

    2011-09-01

    Interest in Adaptive Coded Aperture Imaging (ACAI) continues to grow as the optical and systems engineering community becomes increasingly aware of ACAI's potential benefits in the design and performance of both imaging and non-imaging systems , such as good angular resolution (IFOV), wide distortion-free field of view (FOV), excellent image quality, and light weight construct. In this presentation we first review the accomplishments made over the past five years, then expand on previously published work to show how replacement of conventional imaging optics with coded apertures can lead to a reduction in system size and weight. We also present a trade space analysis of key design parameters of coded apertures and review potential applications as replacement for traditional imaging optics. Results will be presented, based on last year's work of our investigation into the trade space of IFOV, resolution, effective focal length, and wavelength of incident radiation for coded aperture architectures. Finally we discuss the potential application of coded apertures for replacing objective lenses of night vision goggles (NVGs).

  20. Diopside (CaO-MgO-2SiO2)-fluorapatite (9CaO-3P2O5-CaF2) glass-ceramics: Potential materials for bone tissue engineering

    SciTech Connect

    Kansal, Ishu; Goel, Ashutosh; Tulyaganov, Dilshat U.; Pascual, Maria J.; Lee, Hye-Young; Kim, Hae-Won; Ferreira, Jose M.

    2011-08-18

    Glass-ceramics in the diopside (CaMgSi2O6) - fluorapatite [Ca5(PO4)3F] system are potential candidates for restorative dental and bone implant materials. In the present study, a series of glasses along diopside - fluorapatite binary system have been prepared with varying diopside/fluorapatite ratios for their potential applications in bone tissue engineering. The glasses were obtained from compositions with fluorapatite contents varying between 0-40 wt.%. The sintering ability and crystallization kinetics of as obtained amorphous glasses have been studied through hot-stage microscopy (HSM) and differential thermal analysis (DTA), respectively while crystalline phase evolution in sintered GCs has been followed by X-ray diffraction (XRD) adjoined with Rietveld-R.I.R. technique and scanning electron microscopy (SEM). Further, biodegradation and apatite forming ability of glass-ceramics were investigated by immersion of glass-ceramic discs in simulated body fluid (SBF) solution while chemical degradation and weight loss of glass-ceramics were studied by immersion in Tris-HCl in accordance with standard ISO 10993-14. The addition of fluorapatite (10-25 wt.%) in diopside glass system significantly enhanced the sintering ability of glass-ceramics and improved their apatite forming ability along with their biodegradation behaviour. Moreover, the in vitro cellular responses to glass-ceramics showed good cell viability and significant stimulation of osteoblastic differentiation, suggesting the possible use of the glass-ceramics for bone regeneration.

  1. Optimized demineralization of human cancellous bone by application of a vacuum.

    PubMed

    Eagle, Mark J; Rooney, Paul; Kearney, John N

    2015-07-01

    Human demineralized bone matrix derived from cortical bone is used by surgeons due to its ability to promote bone formation. There is also a need for shaped demineralized bone matrices made from cancellous bone, where the properties of the material allow its insertion into defects, therefore acting as a void filler and scaffold onto which new bone can form. In this study, we report that demineralized bone sponges were prepared by dissecting and cutting knee bone into cancellous bone cubes of 1 cm(3) . These cubes were then taken through a series of warm water washes, some with sonication, centrifugation, and two decontamination chemical washes. The cubes were optimally demineralized into sponges with 0.5N hydrochloric acid under vacuum with constant pH measurement. Demineralization was confirmed by quantitative measurement of calcium and qualitatively by compression. The sponges were freeze dried before terminal sterilisation with a target dose of 25 kGy gamma radiation whilst frozen. Samples of the sponges were histologically examined for calcium and collagen and also tested for osteoinductivity. Data showed well defined collagen staining in the sponges, with little residual calcium. Sponges from two out of three donors demonstrated osteoinductivity when implanted into the muscle of an athymic mouse.

  2. Design and fabrication of a flexible large area fabric transducer for bone healing application

    NASA Astrophysics Data System (ADS)

    Jadidian, Bahram

    The electromechanical transducers have found applications in their either passive or active modes. These applications include hydrophone, medical imaging, nondestructive evaluation, motors, sensors, actuators, civil and aerospace engineering. Other medical applications for ultrasonic transducers include therapeutics, osteosynthesis, lithotripsy, thrombolysis, and transdermal drug administration. During the past few decades, lead zirconate titanate (PZT), has been utilized in transducer applications in the form of a bulk piezoelectric ceramic and/or ceramic-polymer composites because of its high piezoelectric charge coefficient d33. The usage of piezoelectric ceramic/polymer composites allows designers to overcome some of the problems dealing with either monolithic piezoceramics or piezopolymers in transducer applications. In this work, a variety of composites with different connectivity patterns were formed. Composites with 1-3 connectivity were fabricated using bundling and collimating methods. Sized and unsized fibers were woven to form fabric. The fabric was used to form 3-3 composites and spiral structures. Square sheets of the fabric were laminated on top of each other, heat treated, and embedded in different types of polymer. The effect of applied pressure on the stack during heat treatment was studied. Plane fabric was formed in the spiral manner and used to construct piezocomposites. A piezoelectric transducer with high thickness coupling coefficient and its matching layer were exploited for bone healing application. One of the structures with the highest electromechanical properties, developed in this work, was chosen for the array fabrication. The spiral composite elements, with the best properties, were arranged in a 3 x 4 format embedded in a flexible polymer. The mechanical endurance of the elements and the array was studied. A large area flexible matching layer with low attenuation was developed. An extensive study was performed to determine the

  3. Biopolymeric hydrogels - nanostructured TiO2 hybrid materials as potential injectable scaffolds for bone regeneration.

    PubMed

    Zazakowny, Karolina; Lewandowska-Łańcucka, Joanna; Mastalska-Popławska, Joanna; Kamiński, Kamil; Kusior, Anna; Radecka, Marta; Nowakowska, Maria

    2016-12-01

    The present work aims at development of novel hybrid materials from genipin crosslinked collagen or collagen/chitosan hydrogels containing various types of TiO2 nanoparticles characterized with different anatase/rutile ratios. Collagen and chitosan were selected as hydrogel components since they are biopolymers being, like collagen, the major compound present in extracellular matrix or exhibit structural similarity to glycosaminoglycans, like chitosan. TiO2 nanoparticles were introduced to the hydrogel matrices to improve their mechanical properties as well as bioactivity. A series of twelve novel hybrid materials were prepared and their physicochemical, mechanical and biological properties were evaluated. It was found that TiO2 nanostructures introduced to the hydrogels have significant influence on the swelling properties of the synthesized hybrids and their impact is strongly dependent on the type of matrices. The surfaces of hybrid materials were found to be more hydrophilic than these of corresponding hydrogel matrix. It was also observed that, the storage modulus values of the hybrids based on collagen-chitosan hydrogel are comparable to these for plain hydrogels what indicates that the mechanical properties of the materials obtained are satisfactory for possible biomedical application. The in vitro cell culture studies have shown that prepared materials are biocompatible as they can support mitochondrial activity of MEFs as well as MG-63 cells. In vitro experiments performed under simulated body fluid (SBF) conditions have revealed that all studied TiO2 nanoparticles present in hydrogel matrices, regardless of anatase/rutile ratio, successfully induced formation of apatite-like structures. The hybrid materials developed here are promising candidates for preparation of bioactive, injectable scaffolds for tissue engineering.

  4. Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart.

    PubMed

    Igura, Koichi; Okada, Motoi; Kim, Ha Won; Ashraf, Muhammad

    2013-11-01

    Stem cell-mediated cardiac regeneration is impaired with age. In this study, we identified a novel subpopulation of small juvenile stem cells (SJSCs) isolated from aged bone marrow-derived stem cells (BMSCs) with high proliferation and differentiation potential. SJSCs expressed mesenchymal stem cell markers, CD29(+)/CD44(+)/CD59(+)/CD90(+), but were negative for CD45(-)/CD117(-) as examined by flow cytometry analysis. SJSCs showed higher proliferation, colony formation, and differentiation abilities compared with BMSCs. We also observed that SJSCs significantly expressed cardiac lineage markers (Gata-4 and myocyte-specific enhancer factor 2C) and pluripotency markers (octamer-binding transcription factor 4, sex-determining region Y box 2, stage-specific embryonic antigen 1, and Nanog) as well as antiaging factors such as telomerase reverse transcriptase and sirtuin 1. Interestingly, SJSCs either from young or aged animals showed significantly longer telomere length as well as lower senescence-associated β-galactosidase expression, suggesting that SJSCs possess antiaging properties, whereas aged BMSCs have limited potential for proliferation and differentiation. Furthermore, transplantation of aged SJSCs into the infarcted rat heart significantly reduced the infarction size and improved left ventricular function, whereas transplantation of aged BMSCs was less effective. Moreover, neovascularization as well as cardiomyogenic differentiation in the peri-infarcted area were significantly increased in the SJSC-transplanted group compared with the BMSC-transplated group, as evaluated by immunohistochemical analysis. Taken together, these findings demonstrate that SJSCs possess characteristics of antiaging, pluripotency, and high proliferation and differentiation rates, and, therefore, these cells offer great therapeutic potential for repair of the injured myocardium.

  5. Microbial aspartic proteases: current and potential applications in industry.

    PubMed

    Theron, Louwrens W; Divol, Benoit

    2014-11-01

    Aspartic proteases are a relatively small group of proteolytic enzymes that are active in acidic environments and are found across all forms of life. Certain microorganisms secrete such proteases as virulence agents and/or in order to break down proteins thereby liberating assimilable sources of nitrogen. Some of the earlier applications of these proteolytic enzymes are found in the manufacturing of cheese where they are used as milk-clotting agents. Over the last decade, they have received tremendous research interest because of their involvement in human diseases. Furthermore, there has also been a growing interest on these enzymes for their applications in several other industries. Recent research suggests in particular that they could be used in the wine industry to prevent the formation of protein haze while preserving the wines' organoleptic properties. In this mini-review, the properties and mechanisms of action of aspartic proteases are summarized. Thereafter, a brief overview of the industrial applications of this specific class of proteases is provided. The use of aspartic proteases as alternatives to clarifying agents in various beverage industries is mentioned, and the potential applications in the wine industry are thoroughly discussed.

  6. Bacterial and Fungal Proteolytic Enzymes: Production, Catalysis and Potential Applications.

    PubMed

    da Silva, Ronivaldo Rodrigues

    2017-02-03

    Submerged and solid-state bioprocesses have been extensively explored worldwide and employed in a number of important studies dealing with microbial cultivation for the production of enzymes. The development of these production technologies has facilitated the generation of new enzyme-based products with applications in pharmaceuticals, food, bioactive peptides, and basic research studies, among others. The applicability of microorganisms in biotechnology is potentiated because of their various advantages, including large-scale production, short time of cultivation, and ease of handling. Currently, several studies are being conducted to search for new microbial peptidases with peculiar biochemical properties for industrial applications. Bioprospecting, being an important prerequisite for research and biotechnological development, is based on exploring the microbial diversity for enzyme production. Limited information is available on the production of specific proteolytic enzymes from bacterial and fungal species, especially on the subgroups threonine and glutamic peptidases, and the seventh catalytic type, nonhydrolytic asparagine peptide lyase. This gap in information motivated the present study about these unique biocatalysts. In this study, the biochemical and biotechnological aspects of the seven catalytic types of proteolytic enzymes, namely aspartyl, cysteine, serine, metallo, glutamic, and threonine peptidase, and asparagine peptide lyase, are summarized, with an emphasis on new studies, production, catalysis, and application of these enzymes.

  7. Graphene-plasmon polaritons: From fundamental properties to potential applications

    NASA Astrophysics Data System (ADS)

    Xiao, Sanshui; Zhu, Xiaolong; Li, Bo-Hong; Mortensen, N. Asger

    2016-04-01

    With unique possibilities for controlling light in nanoscale devices, graphene plasmonics has opened new perspectives to the nanophotonics community with potential applications in metamaterials, modulators, photodetectors, and sensors. In this paper, we briefly review the recent exciting progress in graphene plasmonics. We begin with a general description of the optical properties of graphene, particularly focusing on the dispersion of graphene-plasmon polaritons. The dispersion relation of graphene-plasmon polaritons of spatially extended graphene is expressed in terms of the local response limit with an intraband contribution. With this theoretical foundation of graphene-plasmon polaritons, we then discuss recent exciting progress, paying specific attention to the following topics: excitation of graphene plasmon polaritons, electron-phonon interactions in graphene on polar substrates, and tunable graphene plasmonics with applications in modulators and sensors. Finally, we address some of the apparent challenges and promising perspectives of graphene plasmonics.

  8. Nanotechnology and stem cell therapy for cardiovascular diseases: potential applications.

    PubMed

    La Francesca, Saverio

    2012-01-01

    The use of stem cell therapy for the treatment of cardiovascular diseases has generated significant interest in recent years. Limitations to the clinical application of this therapy center on issues of stem cell delivery, engraftment, and fate. Nanotechnology-based cell labeling and imaging techniques facilitate stem cell tracking and engraftment studies. Nanotechnology also brings exciting new opportunities to translational stem cell research as it enables the controlled engineering of nanoparticles and nanomaterials that can properly relate to the physical scale of cell-cell and cell-niche interactions. This review summarizes the most relevant potential applications of nanoscale technologies to the field of stem cell therapy for the treatment of cardiovascular diseases.

  9. Stimuli-responsive Pickering emulsions: recent advances and potential applications.

    PubMed

    Tang, Juntao; Quinlan, Patrick James; Tam, Kam Chiu

    2015-05-14

    Pickering emulsions possess many advantages over traditional surfactant stabilized emulsions. For example, Pickering emulsions impart better stability against coalescence and, in many cases, are biologically compatible and environmentally friendly. These characteristics open the door for their use in a variety of industries spanning petroleum, food, biomedicine, pharmaceuticals, and cosmetics. Depending on the application, rapid, but controlled stabilization and destabilization of an emulsion may be necessary. As a result, Pickering emulsions with stimuli-responsive properties have, in recent years, received a considerable amounts of attention. This paper provides a concise and comprehensive review of Pickering emulsion systems that possess the ability to respond to an array of external triggers, including pH, temperature, CO2 concentration, light intensity, ionic strength, and magnetic field. Potential applications for which stimuli-responsive Pickering emulsion systems would be of particular value, such as emulsion polymerization, enhanced oil recovery, catalyst recovery, and cosmetics, are discussed.

  10. 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

  11. Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standarizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

    DTIC Science & Technology

    2008-08-01

    To better understand the cellular basis of a long bone defect, we have utilized the GFP reporters in the closed tibial fracture. The surprise finding...callus. In the coming year we will apply the information learned from the calvarial defect to a non-union extension of the tibial fracture model...initiated a comprehensive examination of the tibial fracture model in mice bearing GFP reporters of lineage progression. This project has been assumed

  12. [Ecological memory and its potential applications in ecology: a review].

    PubMed

    Sun, Zhong-yu; Ren, Hai

    2011-03-01

    Ecological memory (EM) is defined as the capability of the past states or experiences of a community to influence the present or future ecological responses of the community. As a relatively new concept, EM has received considerable attention in the study of ecosystem structure and function, such as community succession, ecological restoration, biological invasion, and natural resource management. This review summarized the definition, components, and categories of EM, and discussed the possible mechanisms and affecting factors of EM. Also, the potential applications of EM were proposed, in order to further understand the mechanisms of community succession and to guide ecological restoration.

  13. Potential applications of an electron cyclotron resonance multicusp plasma source

    SciTech Connect

    Tsai, C.C.; Berry, L.A.; Gorbatkin, S.M.; Haselton, H.H.; Roberto, J.B.; Stirling, W.L.

    1989-01-01

    An electron cyclotron resonance (ECR) multicusp plasmatron has been developed by feeding a multicusp bucket arc chamber with a compact ECR plasma source. This novel source produced large (about 25-cm-diam), uniform (to within {plus minus}10%), dense (>10{sup 11}-cm{sup -3}) plasmas of argon, helium, hydrogen, and oxygen. It has been operated to produce an oxygen plasma for etching 12.7-cm (5-in.) positive photoresist-coated silicon wafers with uniformity within {plus minus}8%. Results and potential applications of this new ECR plasma source for plasma processing of thin films are discussed. 21 refs., 10 figs.

  14. Clinical application of vestibular evoked myogenic potential (VEMP).

    PubMed

    Murofushi, Toshihisa

    2016-08-01

    The author reviewed clinical aspects of vestibular evoked myogenic potentials (VEMPs). Now two types of VEMPs are available. The first one is cervical VEMP, which is recorded in the sternocleidomastoid muscle and predominantly reflects sacculo-collic reflex. The other is ocular VEMP, which is usually recorded below the lower eye lid and predominantly reflects utriculo-ocular reflex. VEMPs play important roles not only for assessment of common vestibular diseases but also for establishment of new clinical entities. Clinical application in Meniere's disease, vestibular neuritis, benign paroxysmal positional vertigo, vestibular migraine, idiopathic otolithic vertigo, and central vertigo/dizziness was reviewed.

  15. Carbon nanotubes: a potential concept for drug delivery applications.

    PubMed

    Kumar, Rakesh; Dhanawat, Meenakshi; Kumar, Sudhir; Singh, Brahma N; Pandit, Jayant K; Sinha, Vivek R

    2014-04-01

    The unique properties of carbon nanotubes (CNTs) make them a highly interesting and demandable nanocarrier in the field of nanoscience. CNTs facilitate efficient delivery of therapeutics like drugs, proteins, genes, nucleic acids, vitamins and lot more. Even though highly beneficial, the biocompatibility of CNTs is a major issue in their questioning their potential application in targeting drug delivery. Studies confirmed subdued toxicity of CNTs following slight modifications like functionalization, controlled dimensions, purification etc. A well-established mechanism for cellular internalization is an insistent need to attain a more efficient and targeted delivery. Recent patents have been thoroughly discussed in the text below.

  16. Higher order statistical moment application for solar PV potential analysis

    NASA Astrophysics Data System (ADS)

    Basri, Mohd Juhari Mat; Abdullah, Samizee; Azrulhisham, Engku Ahmad; Harun, Khairulezuan

    2016-10-01

    Solar photovoltaic energy could be as alternative energy to fossil fuel, which is depleting and posing a global warming problem. However, this renewable energy is so variable and intermittent to be relied on. Therefore the knowledge of energy potential is very important for any site to build this solar photovoltaic power generation system. Here, the application of higher order statistical moment model is being analyzed using data collected from 5MW grid-connected photovoltaic system. Due to the dynamic changes of skewness and kurtosis of AC power and solar irradiance distributions of the solar farm, Pearson system where the probability distribution is calculated by matching their theoretical moments with that of the empirical moments of a distribution could be suitable for this purpose. On the advantage of the Pearson system in MATLAB, a software programming has been developed to help in data processing for distribution fitting and potential analysis for future projection of amount of AC power and solar irradiance availability.

  17. Bone densitometry.

    PubMed

    Chun, Kwang J

    2011-05-01

    Conventional radiographic methods allow physicians to visualize bone structure. However, they do not offer information on the bone mineral density (BMD), which can facilitate early diagnosis and treatment of osteoporosis. Bone densitometry, by contrast, helps to detect bone mineral loss at an early stage because it provides accurate quantitative measurement of BMD. With an emphasis on quantification, shorter scanning time and precision, scientists have been developing BMD measurement devices that use absorption technique. They first developed single-energy absorptiometry (single-photon absorptiometry) by using I-125, which could measure BMD of peripheral bones. Single-photon absorptiometry was replaced by dual-energy absorptiometry (dual photon absorptiometry [DPA]) that used gadolinium-153. DPA had greater accuracy in measuring the BMD of central skeletal bones. Single-energy x-ray absorptiometry was also developed but it had limitations in measuring central skeletal BMD. In the mid-1980s, dual-energy x-ray absorptiometry (DXA) was introduced and widely accepted for the early detection, treatment, and follow-up study of osteoporosis. There are several reasons for the popularity. DXA can measure BMD of posteroanterior spine and hip in a much shorter time than DPA while being capable of measuring BMD of peripheral bones. Other advantages include very low radiation doses to the patients, high image resolution, precision, and stable calibration of the instruments. In recent years, DXA has also been applied to lateral spine for the density of trabecular bone, to the whole body for the measurement of total body bone density and for the body composition, and to the spine for the vertebral fracture assessment. Still, posteroanterior spine and hip scans remain the most common applications of DXA because data on the normal range of BMD of the skeletal sites for different age, sex, and ethnic groups are compiled and made available with the devices, which gives the physician

  18. Application potential of toll-like receptors in cancer immunotherapy

    PubMed Central

    Shi, Ming; Chen, Xi; Ye, Kangruo; Yao, Yuanfei; Li, Yu

    2016-01-01

    Abstract Toll-like receptors (TLRs), as the most important pattern recognition receptors in innate immunity, play a pivotal role in inducing immune response through recognition of microbial invaders or specific agonists. Recent studies have suggested that TLRs could serve as important regulators in the development of a variety of cancer. However, increasing evidences have shown that TLRs may display quite opposite outcomes in cancer development. Although several potential therapeutic Toll-like receptor ligands have been found, the mechanism and therapy prospect of TLRs in cancer development has to be further elucidated to accelerate the clinical application. By performing a systematic review of the present findings on TLRs in cancer immunology, we attempted to evaluate the therapeutic potential of TLRs in cancer therapy and elucidate the potential mechanism of cancer progress regulated by TLR signaling and the reported targets on TLRs for clinical application. An electronic databases search was conducted in PubMed, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database from their inception to February 1, 2016. The following keywords were used to search the databases: Toll-like receptors, cancer therapy, therapeutic target, innate immunity. Of 244 studies that were identified, 97 nonrelevant studies were excluded. In total, 147 full-text articles were assessed, and from these, 54 were excluded as they did not provide complete key information. Thus, 93 studies were considered eligible and included in the analysis. According to the data from the included trials, 14 TLR ligands (77.8%) from 82 studies have been demonstrated to display antitumor property in various cancers, whereas 4 ligands (22.2%) from 11 studies promote tumors. Among them, only 3 TLR ligands have been approved for cancer therapy, and 9 ligands were in clinical trials. In addition, the potential mechanism of recently reported targets on TLRs for clinical application was also

  19. Application of ToxCast to evaluate potential biological effects ...

    EPA Pesticide Factsheets

    With the development of “high throughput” in-vitro biological assays, screening-level information on potential adverse biological effects is available for a rapidly increasing number of chemicals. The U.S. EPA ToxCast program has now evaluated several thousand chemicals with more than 800 assays. The original intent of this data was to evaluate potential for human health effects, but it is now being extended to environmental health evaluations. The R package ToxEval was developed as a screening tool to use ToxCast results for evaluation of potential adverse biological effects from trace organic chemicals in water samples. Using ToxEval, trace organic chemical data from water samples and passive samplers collected at 57 Great Lakes tributaries from 2010-2013 were examined to determine the tributaries with the greatest potential for adverse biological effects wit